Elucidating the mechanism of toxicity is crucial in drug safety evaluations. TOXic Process Ontology (TXPO) systematizes a wide variety of terms involving toxicity courses and processes. The first version of TXPO focuses on liver toxicity. The TXPO contains an is-a hierarchy that is organized into three layers: the top layer contains general terms, mostly derived from the Basic Formal Ontology. The intermediate layer contains biomedical terms in OBO foundry from UBERON, Cell Ontology, NCBI Taxon, ChEBI, Gene Ontology, PATO, OGG, INOH, HINO, NCIT, DOID and Relational ontology (RO). The lower layer contains toxicological terms. In applied work, we have developed a prototype of TOXPILOT, a TOXic Process InterpretabLe knOwledge sysTem. TOXPILOT provides visualization maps of the toxic course, which facilitates capturing the comprehensive picture for understanding toxicity mechanisms. A prototype of TOXPILOT is available: https://toxpilot.nibiohn.go.jp
An extension version ontology, which focuses on the homeostasis imbalance process affected by drugs, viruses, and other factors, is available: Homeostasis imbalance process (HoIP) ontology https://bioportal.bioontology.org/ontologies/HOIP
For external terms/classes, the ontology from which the term was imported
the symbol assigned by the nomenclature authority
The NCBITaxon ontology ID of an organism.
X is the opposite of y if there exists some distance metric M, and there exists no z such as M(x,z) <= M(x,y) or M(y,z) <= M(y,x).
Notes on the homology status of this class.
This annotation property may be replaced with an annotation property from an external ontology such as IAO
Notes on the how instances of this class vary across species.
Notes on the evolved function of instances of this class.
Notes on the structure, composition or histology of instances of this class.
Notes on the ontogenic development of instances of this class.
Recommended best practice is to use RFC 3066 [RFC3066], which, in conjunction with ISO 639 [ISO639], defines two- and three-letter primary language tags with optional subtags. Examples include "en" or "eng" for English, "akk" for Akkadian, and "en-GB" for English used in the United Kingdom.
A language of the intellectual content of the resource.
my brain is part of my body (continuant parthood, two material entities)
my stomach cavity is part of my stomach (continuant parthood, immaterial entity is part of material entity)
this day is part of this year (occurrent parthood)
a core relation that holds between a part and its whole
Everything is part of itself. Any part of any part of a thing is itself part of that thing. Two distinct things cannot be part of each other.
Occurrents are not subject to change and so parthood between occurrents holds for all the times that the part exists. Many continuants are subject to change, so parthood between continuants will only hold at certain times, but this is difficult to specify in OWL. See https://code.google.com/p/obo-relations/wiki/ROAndTime
Parthood requires the part and the whole to have compatible classes: only an occurrent can be part of an occurrent; only a process can be part of a process; only a continuant can be part of a continuant; only an independent continuant can be part of an independent continuant; only an immaterial entity can be part of an immaterial entity; only a specifically dependent continuant can be part of a specifically dependent continuant; only a generically dependent continuant can be part of a generically dependent continuant. (This list is not exhaustive.) A continuant cannot be part of an occurrent: use 'participates in'. An occurrent cannot be part of a continuant: use 'has participant'. A material entity cannot be part of an immaterial entity: use 'has location'. A specifically dependent continuant cannot be part of an independent continuant: use 'inheres in'. An independent continuant cannot be part of a specifically dependent continuant: use 'bearer of'.
my body has part my brain (continuant parthood, two material entities)
my stomach has part my stomach cavity (continuant parthood, material entity has part immaterial entity)
a core relation that holds between a whole and its part
Parthood requires the part and the whole to have compatible classes: only an occurrent have an occurrent as part; only a process can have a process as part; only a continuant can have a continuant as part; only an independent continuant can have an independent continuant as part; only a specifically dependent continuant can have a specifically dependent continuant as part; only a generically dependent continuant can have a generically dependent continuant as part. (This list is not exhaustive.) A continuant cannot have an occurrent as part: use 'participates in'. An occurrent cannot have a continuant as part: use 'has participant'. An immaterial entity cannot have a material entity as part: use 'location of'. An independent continuant cannot have a specifically dependent continuant as part: use 'bearer of'. A specifically dependent continuant cannot have an independent continuant as part: use 'inheres in'.
b occurs_in c =def b is a process and c is a material entity or immaterial entity& there exists a spatiotemporal region r and b occupies_spatiotemporal_region r.& forall(t) if b exists_at t then c exists_at t & there exist spatial regions s and s’ where & b spatially_projects_onto s at t& c is occupies_spatial_region s’ at t& s is a proper_continuant_part_of s’ at t
Paraphrase of definition: a relation between a process and an independent continuant, in which the process takes place entirely within the independent continuant
a relation between a continuant and a process, in which the process takes place entirely within the independent continuant
[copied from inverse property 'occurs in'] b occurs_in c =def b is a process and c is a material entity or immaterial entity& there exists a spatiotemporal region r and b occupies_spatiotemporal_region r.& forall(t) if b exists_at t then c exists_at t & there exist spatial regions s and s’ where & b spatially_projects_onto s at t& c is occupies_spatial_region s’ at t& s is a proper_continuant_part_of s’ at t
a relation between a gene and the organism where this gene belongs to the organism in nature. It does not include a foreign gene that is transferred to an organism by a genetic engineering method.
a relation between a specifically dependent continuant (the dependent) and an independent continuant (the bearer), in which the dependent specifically depends on the bearer for its existence
A dependent inheres in its bearer at all times for which the dependent exists.
a relation between an independent continuant (the bearer) and a specifically dependent continuant (the dependent), in which the dependent specifically depends on the bearer for its existence
this blood clot participates in this blood coagulation
this input material (or this output material) participates in this process
this investigator participates in this investigation
a relation between a continuant and a process, in which the continuant is somehow involved in the process
a relation between a process and a continuant, in which the continuant is somehow involved in the process
Example: Protein refolding process hasParticipant "GRP78/Bip" that has a chaperon role .
this catalysis function is a function of this enzyme
A relation between a function and an independent continuant (the bearer), in which the function specifically depends on the bearer for its existence
this red color is a quality of this apple
a relation between a quality and an independent continuant (the bearer), in which the quality specifically depends on the bearer for its existence
A quality inheres in its bearer at all times for which the quality exists.
this investigator role is a role of this person
a relation between a role and an independent continuant (the bearer), in which the role specifically depends on the bearer for its existence
A role inheres in its bearer at all times for which the role exists, however the role need not be realized at all the times that the role exists.
a relation between an independent continuant (the bearer) and a function, in which the function specifically depends on the bearer for its existence
A bearer can have many functions, and its functions can exist for different periods of time, but none of its functions can exist when the bearer does not exist. A function need not be realized at all the times that the function exists.
a relation between an independent continuant (the bearer) and a quality, in which the quality specifically depends on the bearer for its existence
hasQuality is a relation between an entity and the quality that it bears.
a relation between an independent continuant (the bearer) and a role, in which the role specifically depends on the bearer for its existence
A bearer can have many roles, and its roles can exist for different periods of time, but none of its roles can exist when the bearer does not exist. A role need not be realized at all the times that the role exists.
A part of relation that applies only between occurents.
relation between an artery and the structure is supplies with blood
W 'has component' p if w 'has part' p and w is such that it can be directly disassembled into into n parts p, p2, p3, ..., pn, where these parts are of similar type.
process(P1) regulates process(P2) iff: P1 results in the initiation or termination of P2 OR affects the frequency of its initiation or termination OR affects the magnitude or rate of output of P2.
Process(P1) negatively regulates process(P2) iff: P1 terminates P2, or P1 descreases the the frequency of initiation of P2 or the magnitude or rate of output of P2.
Process(P1) postively regulates process(P2) iff: P1 initiates P2, or P1 increases the the frequency of initiation of P2 or the magnitude or rate of output of P2.
P has output c iff c is a participant in p, c is present at the beginning of p.
P has output c iff c is a participant in p, c is present at the end of p
inverse of regulates: process(P1) regulates process(P2) iff: P1 results in the initiation or termination of P2 OR affects the frequency of its initiation or termination OR affects the magnitude or rate of output of P2.
inverse of negatively regulates: Process(P1) negatively regulates process(P2) iff: P1 terminates P2, or P1 descreases the the frequency of initiation of P2 or the magnitude or rate of output of P2.
inverse of positively regulates: Process(P1) postively regulates process(P2) iff: P1 initiates P2, or P1 increases the the frequency of initiation of P2 or the magnitude or rate of output of P2.
This relationship holds between p and l when p is a transport or localization process in which the outcome is to move some cargo c from some initial location l to some destination.
This relationship holds between p and l when p is a transport or localization process in which the outcome is to move some cargo c from a an initial location to some destination.
An organism that is a member of a population of organisms
is member of is a mereological relation between a item and a collection.
has member is a mereological relation between a collection and an item.
'input of' is a relation between a participant and a process, where the participant is present at the start of the process.
'output of' is a relation between a participant and a process, where the participant is present at the end of the process.
p 'causally upstream or within' q iff (1) the end of p is before the end of q and (2) the execution of p exerts some causal influence over the outputs of q; i.e. if p was abolished or the outputs of p were to be modified, this would necessarily affect q.
inverse of causally upstream of or within: p 'causally upstream or within' q iff (1) the end of p is before the end of q and (2) the execution of p exerts some causal influence over the outputs of q; i.e. if p was abolished or the outputs of p were to be modified, this would necessarily affect q.
x composed_primarily_of_y if:more than half of the mass of x is made from parts of y
p is causally related to q if and only if p or any part of p and q or any part of q are linked by a chain of events where each event pair is one of direct activation or direct inhibition. p may be upstream, downstream, part of or a container of q.
Holds between c and p if and only if c is capable of some activity a, and a regulates p.
Holds between c and p if and only if c is capable of some activity a, and a positively regulates p.
Holds between c and p if and only if c is capable of some activity a, and a negatively regulates p.
a relation between a toxic course (the bearer) and a process. Core process is a crucial process to the manifestation of toxicity and depends on the bearer for its existence.
'Metafunctioning type of' is a relation between the type of metafunctioning and functioning process. Metafunctioning is a functional process to other process, for example, preventing, controlling and so on.
'has molecular reaction' is a relation that holds between a whole occurrent (process) and its molecular process.
'finding of' is a relation between a finding and an entity, where the finding is a representational artifact that a result of a laboratory test or an observation.
'component of' is a relation between molecular components and a molecular complex.
inverse of 'has cause': p 'has cause' q if p exerts some causal influence on q directly, where p is a cause and q is its effect.
p 'has cause' q if p exerts some causal influence on q directly, where p is a cause and q is its effect.
'Relation between a role and a process' is a relationship that holds between a role of material entity and a process in which causality is involved, with either the material entity or some part of the material entity plays a role and some influence over the process.
'manifested phenotype of' is a relation between a phenotype and an entity, where there is a bearer of the realizable entity that participates in the process, and the phenotype comes to be realized in the course of the process.
This shattering realizes the fragility in the course of breaking the cup (process).
'mainfests phenotype' is a relation between an entity and quality, where there is a bearer of the realizable entity that participates in the process, and the phenotype comes to be realized in the course of the process.
Inherit means to receive a property (or an attribute and its value) from another entity (other than the ancestor) .
'has family member' is a relation between (molecule ) family and a molecule.
A protein family is a group of evolutionarily-related proteins. In many cases a protein family has a corresponding gene family.
'dysfunctioning of' is a relation between an impaired or abnormal functioning and a normal functioning process.
'molecular reaction of' is a relation that holds between a molecular process and its whole process.
'relates assay' is a relation between an entity and the assay in which the entity was related (e.g., can be expressed, observed, and so on).
'has context' is a relation between an entity and its context dependent on. Role is intrinsically context-dependent.
'has related human gene' is a relation between a molecule and the related gene.
The cross-sectional area of the coronary artery has attribute value 'small.'
'has attribute value' is a relation between an attribute and its value.
'dysfunctioning of' is a relation between an increasing function process and a normal one.
'malfunctioning of' is a relation between an abnormal functioning and a normal functioning process.
'has state' is a relation between an entity and the state.
'has attribute' is a relation between an entity and its attribute, in which the attribute specifically depends on the bearer for its existence.
'has agent' is a relation between a participant and a process, in which the participant is active in the relevant process.
Example: A protease is an agent in proteolysis process.
Metafunctioning type is a relation between functional process and the type of metafunction. Metafunctioning is a functional process to other process, for example, preventing, controlling and so on.
'property of' is a relation between a property and the entity, , in which the property specifically depends on the bearer for its existence.
'is attribute of' is a relation that associates an attribute with an entity.
'has finding' is a relation between an entity and its finding, where the finding is a representational artifact that a result of a laboratory test or an observation.
Proteolysis is a context of the protease role of the molecule.
'context of' is a relation between a context and an entity. Role is intrinsically context-dependent.
'related assay of' is a relationship between an assay and the entity, in which the entity can be related (e.g., can be expressed, observed, and so on) in the assay like in vivo, in vitro or clinical test.
'agent of' is a relation between a participant and a process, in which the participant is active in the relevant process.
'famly of' is a relationship between a molecule and its family.
"has ocurrent part" is a relation that holds between a whole occurrent (process) and its part.
"has pathway" is a relation that holds between a whole occurrent (process) for signaling and its pathway.
'pathway of' is a relation that holds between a pathway and its whole (signaling) process.
'Is substance in organism' is a relation between substance and organism where the substance is existed in.
'has dysfunctioning' is a relation between a normal functioning process and an impaired or abnormal functioning.
'Attribute value of' is a relation between a value and its attribute
A relation between a process/process sequence and a disease.
'channel for' is a relation between a channel that is a passage and an entity such a solvent (e.g., ion) to pass.
BFO 2 Reference: In all areas of empirical inquiry we encounter general terms of two sorts. First are general terms which refer to universals or types:animaltuberculosissurgical procedurediseaseSecond, are general terms used to refer to groups of entities which instantiate a given universal but do not correspond to the extension of any subuniversal of that universal because there is nothing intrinsic to the entities in question by virtue of which they – and only they – are counted as belonging to the given group. Examples are: animal purchased by the Emperortuberculosis diagnosed on a Wednesdaysurgical procedure performed on a patient from Stockholmperson identified as candidate for clinical trial #2056-555person who is signatory of Form 656-PPVpainting by Leonardo da VinciSuch terms, which represent what are called ‘specializations’ in [81
Entity doesn't have a closure axiom because the subclasses don't necessarily exhaust all possibilites. For example Werner Ceusters 'portions of reality' include 4 sorts, entities (as BFO construes them), universals, configurations, and relations. It is an open question as to whether entities as construed in BFO will at some point also include these other portions of reality. See, for example, 'How to track absolutely everything' at http://www.referent-tracking.com/_RTU/papers/CeustersICbookRevised.pdf
An entity is anything that exists or has existed or will exist. (axiom label in BFO2 Reference: [001-001])
BFO 2 Reference: Continuant entities are entities which can be sliced to yield parts only along the spatial dimension, yielding for example the parts of your table which we call its legs, its top, its nails. ‘My desk stretches from the window to the door. It has spatial parts, and can be sliced (in space) in two. With respect to time, however, a thing is a continuant.’ [60, p. 240
Continuant doesn't have a closure axiom because the subclasses don't necessarily exhaust all possibilites. For example, in an expansion involving bringing in some of Ceuster's other portions of reality, questions are raised as to whether universals are continuants
A continuant is an entity that persists, endures, or continues to exist through time while maintaining its identity. (axiom label in BFO2 Reference: [008-002])
if b is a continuant and if, for some t, c has_continuant_part b at t, then c is a continuant. (axiom label in BFO2 Reference: [126-001])
if b is a continuant and if, for some t, cis continuant_part of b at t, then c is a continuant. (axiom label in BFO2 Reference: [009-002])
if b is a material entity, then there is some temporal interval (referred to below as a one-dimensional temporal region) during which b exists. (axiom label in BFO2 Reference: [011-002])
(forall (x y) (if (and (Continuant x) (exists (t) (continuantPartOfAt y x t))) (Continuant y))) // axiom label in BFO2 CLIF: [009-002]
(forall (x y) (if (and (Continuant x) (exists (t) (hasContinuantPartOfAt y x t))) (Continuant y))) // axiom label in BFO2 CLIF: [126-001]
(forall (x) (if (Continuant x) (Entity x))) // axiom label in BFO2 CLIF: [008-002]
(forall (x) (if (Material Entity x) (exists (t) (and (TemporalRegion t) (existsAt x t))))) // axiom label in BFO2 CLIF: [011-002]
BFO 2 Reference: every occurrent that is not a temporal or spatiotemporal region is s-dependent on some independent continuant that is not a spatial region
BFO 2 Reference: s-dependence obtains between every process and its participants in the sense that, as a matter of necessity, this process could not have existed unless these or those participants existed also. A process may have a succession of participants at different phases of its unfolding. Thus there may be different players on the field at different times during the course of a football game; but the process which is the entire game s-depends_on all of these players nonetheless. Some temporal parts of this process will s-depend_on on only some of the players.
Occurrent doesn't have a closure axiom because the subclasses don't necessarily exhaust all possibilites. An example would be the sum of a process and the process boundary of another process.
Simons uses different terminology for relations of occurrents to regions: Denote the spatio-temporal location of a given occurrent e by 'spn[e]' and call this region its span. We may say an occurrent is at its span, in any larger region, and covers any smaller region. Now suppose we have fixed a frame of reference so that we can speak not merely of spatio-temporal but also of spatial regions (places) and temporal regions (times). The spread of an occurrent, (relative to a frame of reference) is the space it exactly occupies, and its spell is likewise the time it exactly occupies. We write 'spr[e]' and `spl[e]' respectively for the spread and spell of e, omitting mention of the frame.
An occurrent is an entity that unfolds itself in time or it is the instantaneous boundary of such an entity (for example a beginning or an ending) or it is a temporal or spatiotemporal region which such an entity occupies_temporal_region or occupies_spatiotemporal_region. (axiom label in BFO2 Reference: [077-002])
Every occurrent occupies_spatiotemporal_region some spatiotemporal region. (axiom label in BFO2 Reference: [108-001])
b is an occurrent entity iff b is an entity that has temporal parts. (axiom label in BFO2 Reference: [079-001])
(forall (x) (if (Occurrent x) (exists (r) (and (SpatioTemporalRegion r) (occupiesSpatioTemporalRegion x r))))) // axiom label in BFO2 CLIF: [108-001]
(forall (x) (iff (Occurrent x) (and (Entity x) (exists (y) (temporalPartOf y x))))) // axiom label in BFO2 CLIF: [079-001]
the bottom right portion of a human torso
b is an independent continuant = Def. b is a continuant which is such that there is no c and no t such that b s-depends_on c at t. (axiom label in BFO2 Reference: [017-002])
For any independent continuant b and any time t there is some spatial region r such that b is located_in r at t. (axiom label in BFO2 Reference: [134-001])
For every independent continuant b and time t during the region of time spanned by its life, there are entities which s-depends_on b during t. (axiom label in BFO2 Reference: [018-002])
(forall (x t) (if (IndependentContinuant x) (exists (r) (and (SpatialRegion r) (locatedInAt x r t))))) // axiom label in BFO2 CLIF: [134-001]
(forall (x t) (if (and (IndependentContinuant x) (existsAt x t)) (exists (y) (and (Entity y) (specificallyDependsOnAt y x t))))) // axiom label in BFO2 CLIF: [018-002]
(iff (IndependentContinuant a) (and (Continuant a) (not (exists (b t) (specificallyDependsOnAt a b t))))) // axiom label in BFO2 CLIF: [017-002]
BFO 2 Reference: Spatial regions do not participate in processes.
Spatial region doesn't have a closure axiom because the subclasses don't exhaust all possibilites. An example would be the union of a spatial point and a spatial line that doesn't overlap the point, or two spatial lines that intersect at a single point. In both cases the resultant spatial region is neither 0-dimensional, 1-dimensional, 2-dimensional, or 3-dimensional.
A spatial region is a continuant entity that is a continuant_part_of spaceR as defined relative to some frame R. (axiom label in BFO2 Reference: [035-001])
All continuant parts of spatial regions are spatial regions. (axiom label in BFO2 Reference: [036-001])
(forall (x y t) (if (and (SpatialRegion x) (continuantPartOfAt y x t)) (SpatialRegion y))) // axiom label in BFO2 CLIF: [036-001]
(forall (x) (if (SpatialRegion x) (Continuant x))) // axiom label in BFO2 CLIF: [035-001]
Temporal region doesn't have a closure axiom because the subclasses don't exhaust all possibilites. An example would be the mereological sum of a temporal instant and a temporal interval that doesn't overlap the instant. In this case the resultant temporal region is neither 0-dimensional nor 1-dimensional
A temporal region is an occurrent entity that is part of time as defined relative to some reference frame. (axiom label in BFO2 Reference: [100-001])
All parts of temporal regions are temporal regions. (axiom label in BFO2 Reference: [101-001])
Every temporal region t is such that t occupies_temporal_region t. (axiom label in BFO2 Reference: [119-002])
(forall (r) (if (TemporalRegion r) (occupiesTemporalRegion r r))) // axiom label in BFO2 CLIF: [119-002]
(forall (x y) (if (and (TemporalRegion x) (occurrentPartOf y x)) (TemporalRegion y))) // axiom label in BFO2 CLIF: [101-001]
(forall (x) (if (TemporalRegion x) (Occurrent x))) // axiom label in BFO2 CLIF: [100-001]
the surface of a sphere-shaped part of space
A two-dimensional spatial region is a spatial region that is of two dimensions. (axiom label in BFO2 Reference: [039-001])
(forall (x) (if (TwoDimensionalSpatialRegion x) (SpatialRegion x))) // axiom label in BFO2 CLIF: [039-001]
the spatiotemporal region occupied by a human life
the spatiotemporal region occupied by a process of cellular meiosis.
the spatiotemporal region occupied by the development of a cancer tumor
A spatiotemporal region is an occurrent entity that is part of spacetime. (axiom label in BFO2 Reference: [095-001])
All parts of spatiotemporal regions are spatiotemporal regions. (axiom label in BFO2 Reference: [096-001])
Each spatiotemporal region at any time t projects_onto some spatial region at t. (axiom label in BFO2 Reference: [099-001])
Each spatiotemporal region projects_onto some temporal region. (axiom label in BFO2 Reference: [098-001])
Every spatiotemporal region occupies_spatiotemporal_region itself.
Every spatiotemporal region s is such that s occupies_spatiotemporal_region s. (axiom label in BFO2 Reference: [107-002])
(forall (r) (if (SpatioTemporalRegion r) (occupiesSpatioTemporalRegion r r))) // axiom label in BFO2 CLIF: [107-002]
(forall (x t) (if (SpatioTemporalRegion x) (exists (y) (and (SpatialRegion y) (spatiallyProjectsOntoAt x y t))))) // axiom label in BFO2 CLIF: [099-001]
(forall (x y) (if (and (SpatioTemporalRegion x) (occurrentPartOf y x)) (SpatioTemporalRegion y))) // axiom label in BFO2 CLIF: [096-001]
(forall (x) (if (SpatioTemporalRegion x) (Occurrent x))) // axiom label in BFO2 CLIF: [095-001]
(forall (x) (if (SpatioTemporalRegion x) (exists (y) (and (TemporalRegion y) (temporallyProjectsOnto x y))))) // axiom label in BFO2 CLIF: [098-001]
a process of cell-division, \ a beating of the heart
p is a process = Def. p is an occurrent that has temporal proper parts and for some time t, p s-depends_on some material entity at t. (axiom label in BFO2 Reference: [083-003])
BFO 2 Reference: The realm of occurrents is less pervasively marked by the presence of natural units than is the case in the realm of independent continuants. Thus there is here no counterpart of ‘object’. In BFO 1.0 ‘process’ served as such a counterpart. In BFO 2.0 ‘process’ is, rather, the occurrent counterpart of ‘material entity’. Those natural – as contrasted with engineered, which here means: deliberately executed – units which do exist in the realm of occurrents are typically either parasitic on the existence of natural units on the continuant side, or they are fiat in nature. Thus we can count lives; we can count football games; we can count chemical reactions performed in experiments or in chemical manufacturing. We cannot count the processes taking place, for instance, in an episode of insect mating behavior.Even where natural units are identifiable, for example cycles in a cyclical process such as the beating of a heart or an organism’s sleep/wake cycle, the processes in question form a sequence with no discontinuities (temporal gaps) of the sort that we find for instance where billiard balls or zebrafish or planets are separated by clear spatial gaps. Lives of organisms are process units, but they too unfold in a continuous series from other, prior processes such as fertilization, and they unfold in turn in continuous series of post-life processes such as post-mortem decay. Clear examples of boundaries of processes are almost always of the fiat sort (midnight, a time of death as declared in an operating theater or on a death certificate, the initiation of a state of war)
Superclass of unit process(primitive process) and senquence processes. It is dissective and has no unity, and hence it can change. It follows A-series of time.
(iff (Process a) (and (Occurrent a) (exists (b) (properTemporalPartOf b a)) (exists (c t) (and (MaterialEntity c) (specificallyDependsOnAt a c t))))) // axiom label in BFO2 CLIF: [083-003]
an atom of element X has the disposition to decay to an atom of element Y
certain people have a predisposition to colon cancer
children are innately disposed to categorize objects in certain ways.
the cell wall is disposed to filter chemicals in endocytosis and exocytosis
BFO 2 Reference: Dispositions exist along a strength continuum. Weaker forms of disposition are realized in only a fraction of triggering cases. These forms occur in a significant number of cases of a similar type.
b is a disposition means: b is a realizable entity & b’s bearer is some material entity & b is such that if it ceases to exist, then its bearer is physically changed, & b’s realization occurs when and because this bearer is in some special physical circumstances, & this realization occurs in virtue of the bearer’s physical make-up. (axiom label in BFO2 Reference: [062-002])
If b is a realizable entity then for all t at which b exists, b s-depends_on some material entity at t. (axiom label in BFO2 Reference: [063-002])
(forall (x t) (if (and (RealizableEntity x) (existsAt x t)) (exists (y) (and (MaterialEntity y) (specificallyDepends x y t))))) // axiom label in BFO2 CLIF: [063-002]
(forall (x) (if (Disposition x) (and (RealizableEntity x) (exists (y) (and (MaterialEntity y) (bearerOfAt x y t)))))) // axiom label in BFO2 CLIF: [062-002]
the disposition of this piece of metal to conduct electricity.
the disposition of your blood to coagulate
the function of your reproductive organs
the role of this boundary to delineate where Utah and Colorado meet
To say that b is a realizable entity is to say that b is a specifically dependent continuant that inheres in some independent continuant which is not a spatial region and is of a type instances of which are realized in processes of a correlated type. (axiom label in BFO2 Reference: [058-002])
All realizable dependent continuants have independent continuants that are not spatial regions as their bearers. (axiom label in BFO2 Reference: [060-002])
(forall (x t) (if (RealizableEntity x) (exists (y) (and (IndependentContinuant y) (not (SpatialRegion y)) (bearerOfAt y x t))))) // axiom label in BFO2 CLIF: [060-002]
(forall (x) (if (RealizableEntity x) (and (SpecificallyDependentContinuant x) (exists (y) (and (IndependentContinuant y) (not (SpatialRegion y)) (inheresIn x y)))))) // axiom label in BFO2 CLIF: [058-002]
A zero-dimensional spatial region is a point in space. (axiom label in BFO2 Reference: [037-001])
(forall (x) (if (ZeroDimensionalSpatialRegion x) (SpatialRegion x))) // axiom label in BFO2 CLIF: [037-001]
the ambient temperature of this portion of air
the length of the circumference of your waist
a quality is a specifically dependent continuant that, in contrast to roles and dispositions, does not require any further process in order to be realized. (axiom label in BFO2 Reference: [055-001])
If an entity is a quality at any time that it exists, then it is a quality at every time that it exists. (axiom label in BFO2 Reference: [105-001])
(forall (x) (if (Quality x) (SpecificallyDependentContinuant x))) // axiom label in BFO2 CLIF: [055-001]
(forall (x) (if (exists (t) (and (existsAt x t) (Quality x))) (forall (t_1) (if (existsAt x t_1) (Quality x))))) // axiom label in BFO2 CLIF: [105-001]
Reciprocal specifically dependent continuants: the function of this key to open this lock and the mutually dependent disposition of this lock: to be opened by this key
of one-sided specifically dependent continuants: the mass of this tomato
of relational dependent continuants (multiple bearers): John’s love for Mary, the ownership relation between John and this statue, the relation of authority between John and his subordinates.
the function of this heart: to pump blood
the mutual dependence of proton donors and acceptors in chemical reactions [79
the mutual dependence of the role predator and the role prey as played by two organisms in a given interaction
the pink color of a medium rare piece of grilled filet mignon at its center
b is a specifically dependent continuant = Def. b is a continuant & there is some independent continuant c which is not a spatial region and which is such that b s-depends_on c at every time t during the course of b’s existence. (axiom label in BFO2 Reference: [050-003])
Specifically dependent continuant doesn't have a closure axiom because the subclasses don't necessarily exhaust all possibilites. We're not sure what else will develop here, but for example there are questions such as what are promises, obligation, etc.
(iff (SpecificallyDependentContinuant a) (and (Continuant a) (forall (t) (if (existsAt a t) (exists (b) (and (IndependentContinuant b) (not (SpatialRegion b)) (specificallyDependsOnAt a b t))))))) // axiom label in BFO2 CLIF: [050-003]
John’s role of husband to Mary is dependent on Mary’s role of wife to John, and both are dependent on the object aggregate comprising John and Mary as member parts joined together through the relational quality of being married.
the role of a boundary to demarcate two neighboring administrative territories
the role of a building in serving as a military target
the role of a stone in marking a property boundary
BFO 2 Reference: One major family of examples of non-rigid universals involves roles, and ontologies developed for corresponding administrative purposes may consist entirely of representatives of entities of this sort. Thus ‘professor’, defined as follows,b instance_of professor at t =Def. there is some c, c instance_of professor role & c inheres_in b at t.denotes a non-rigid universal and so also do ‘nurse’, ‘student’, ‘colonel’, ‘taxpayer’, and so forth. (These terms are all, in the jargon of philosophy, phase sortals.) By using role terms in definitions, we can create a BFO conformant treatment of such entities drawing on the fact that, while an instance of professor may be simultaneously an instance of trade union member, no instance of the type professor role is also (at any time) an instance of the type trade union member role (any more than any instance of the type color is at any time an instance of the type length).If an ontology of employment positions should be defined in terms of roles following the above pattern, this enables the ontology to do justice to the fact that individuals instantiate the corresponding universals – professor, sergeant, nurse – only during certain phases in their lives.
b is a role means: b is a realizable entity & b exists because there is some single bearer that is in some special physical, social, or institutional set of circumstances in which this bearer does not have to be& b is not such that, if it ceases to exist, then the physical make-up of the bearer is thereby changed. (axiom label in BFO2 Reference: [061-001])
(forall (x) (if (Role x) (RealizableEntity x))) // axiom label in BFO2 CLIF: [061-001]
or with divisions drawn by cognitive subjects for practical reasons, such as the division of a cake (before slicing) into (what will become) slices (and thus member parts of an object aggregate). However, this does not mean that fiat object parts are dependent for their existence on divisions or delineations effected by cognitive subjects. If, for example, it is correct to conceive geological layers of the Earth as fiat object parts of the Earth, then even though these layers were first delineated in recent times, still existed long before such delineation and what holds of these layers (for example that the oldest layers are also the lowest layers) did not begin to hold because of our acts of delineation.Treatment of material entity in BFOExamples viewed by some as problematic cases for the trichotomy of fiat object part, object, and object aggregate include: a mussel on (and attached to) a rock, a slime mold, a pizza, a cloud, a galaxy, a railway train with engine and multiple carriages, a clonal stand of quaking aspen, a bacterial community (biofilm), a broken femur. Note that, as Aristotle already clearly recognized, such problematic cases – which lie at or near the penumbra of instances defined by the categories in question – need not invalidate these categories. The existence of grey objects does not prove that there are not objects which are black and objects which are white; the existence of mules does not prove that there are not objects which are donkeys and objects which are horses. It does, however, show that the examples in question need to be addressed carefully in order to show how they can be fitted into the proposed scheme, for example by recognizing additional subdivisions [29
the FMA:regional parts of an intact human body.
the division of the planet into hemispheres
the dorsal and ventral surfaces of the body
the upper and lower lobes of the left lung
BFO 2 Reference: Most examples of fiat object parts are associated with theoretically drawn divisions
b is a fiat object part = Def. b is a material entity which is such that for all times t, if b exists at t then there is some object c such that b proper continuant_part of c at t and c is demarcated from the remainder of c by a two-dimensional continuant fiat boundary. (axiom label in BFO2 Reference: [027-004])
(forall (x) (if (FiatObjectPart x) (and (MaterialEntity x) (forall (t) (if (existsAt x t) (exists (y) (and (Object y) (properContinuantPartOfAt x y t)))))))) // axiom label in BFO2 CLIF: [027-004]
an edge of a cube-shaped portion of space.
A one-dimensional spatial region is a line or aggregate of lines stretching from one point in space to another. (axiom label in BFO2 Reference: [038-001])
(forall (x) (if (OneDimensionalSpatialRegion x) (SpatialRegion x))) // axiom label in BFO2 CLIF: [038-001]
a collection of cells in a blood biobank.
a swarm of bees is an aggregate of members who are linked together through natural bonds
an organization is an aggregate whose member parts have roles of specific types (for example in a jazz band, a chess club, a football team)
defined by fiat: the aggregate of members of an organization
defined through physical attachment: the aggregate of atoms in a lump of granite
defined through physical containment: the aggregate of molecules of carbon dioxide in a sealed container
defined via attributive delimitations such as: the patients in this hospital
the aggregate of bearings in a constant velocity axle joint
the aggregate of blood cells in your body
your collection of Meissen ceramic plates.
An entity a is an object aggregate if and only if there is a mutually exhaustive and pairwise disjoint partition of a into objects
BFO 2 Reference: object aggregates may gain and lose parts while remaining numerically identical (one and the same individual) over time. This holds both for aggregates whose membership is determined naturally (the aggregate of cells in your body) and aggregates determined by fiat (a baseball team, a congressional committee).
ISBN:978-3-938793-98-5pp124-158#Thomas Bittner and Barry Smith, 'A Theory of Granular Partitions', in K. Munn and B. Smith (eds.), Applied Ontology: An Introduction, Frankfurt/Lancaster: ontos, 2008, 125-158.
b is an object aggregate means: b is a material entity consisting exactly of a plurality of objects as member_parts at all times at which b exists. (axiom label in BFO2 Reference: [025-004])
(forall (x) (if (ObjectAggregate x) (and (MaterialEntity x) (forall (t) (if (existsAt x t) (exists (y z) (and (Object y) (Object z) (memberPartOfAt y x t) (memberPartOfAt z x t) (not (= y z)))))) (not (exists (w t_1) (and (memberPartOfAt w x t_1) (not (Object w)))))))) // axiom label in BFO2 CLIF: [025-004]
A three-dimensional spatial region is a spatial region that is of three dimensions. (axiom label in BFO2 Reference: [040-001])
(forall (x) (if (ThreeDimensionalSpatialRegion x) (SpatialRegion x))) // axiom label in BFO2 CLIF: [040-001]
a hole in the interior of a portion of cheese
an air traffic control region defined in the airspace above an airport
your left nostril (a fiat part – the opening – of your left nasal cavity)
b is a site means: b is a three-dimensional immaterial entity that is (partially or wholly) bounded by a material entity or it is a three-dimensional immaterial part thereof. (axiom label in BFO2 Reference: [034-002])
(forall (x) (if (Site x) (ImmaterialEntity x))) // axiom label in BFO2 CLIF: [034-002]
BFO 2 Reference: BFO rests on the presupposition that at multiple micro-, meso- and macroscopic scales reality exhibits certain stable, spatially separated or separable material units, combined or combinable into aggregates of various sorts (for example organisms into what are called ‘populations’). Such units play a central role in almost all domains of natural science from particle physics to cosmology. Many scientific laws govern the units in question, employing general terms (such as ‘molecule’ or ‘planet’) referring to the types and subtypes of units, and also to the types and subtypes of the processes through which such units develop and interact. The division of reality into such natural units is at the heart of biological science, as also is the fact that these units may form higher-level units (as cells form multicellular organisms) and that they may also form aggregates of units, for example as cells form portions of tissue and organs form families, herds, breeds, species, and so on. At the same time, the division of certain portions of reality into engineered units (manufactured artifacts) is the basis of modern industrial technology, which rests on the distributed mass production of engineered parts through division of labor and on their assembly into larger, compound units such as cars and laptops. The division of portions of reality into units is one starting point for the phenomenon of counting.
BFO 2 Reference: Each object is such that there are entities of which we can assert unproblematically that they lie in its interior, and other entities of which we can assert unproblematically that they lie in its exterior. This may not be so for entities lying at or near the boundary between the interior and exterior. This means that two objects – for example the two cells depicted in Figure 3 – may be such that there are material entities crossing their boundaries which belong determinately to neither cell. Something similar obtains in certain cases of conjoined twins (see below).
BFO 2 Reference: To say that b is causally unified means: b is a material entity which is such that its material parts are tied together in such a way that, in environments typical for entities of the type in question,if c, a continuant part of b that is in the interior of b at t, is larger than a certain threshold size (which will be determined differently from case to case, depending on factors such as porosity of external cover) and is moved in space to be at t at a location on the exterior of the spatial region that had been occupied by b at t, then either b’s other parts will be moved in coordinated fashion or b will be damaged (be affected, for example, by breakage or tearing) in the interval between t and t.causal changes in one part of b can have consequences for other parts of b without the mediation of any entity that lies on the exterior of b. Material entities with no proper material parts would satisfy these conditions trivially. Candidate examples of types of causal unity for material entities of more complex sorts are as follows (this is not intended to be an exhaustive list):CU1: Causal unity via physical coveringHere the parts in the interior of the unified entity are combined together causally through a common membrane or other physical covering\. The latter points outwards toward and may serve a protective function in relation to what lies on the exterior of the entity [13, 47
BFO 2 Reference: an object is a maximal causally unified material entity
BFO 2 Reference: ‘objects’ are sometimes referred to as ‘grains’ [74
b is an object means: b is a material entity which manifests causal unity of one or other of the types CUn listed above & is of a type (a material universal) instances of which are maximal relative to this criterion of causal unity. (axiom label in BFO2 Reference: [024-001])
The entries in your database are patterns instantiated as quality instances in your hard drive. The database itself is an aggregate of such patterns. When you create the database you create a particular instance of the generically dependent continuant type database. Each entry in the database is an instance of the generically dependent continuant type IAO: information content entity.
the pdf file on your laptop, the pdf file that is a copy thereof on my laptop
the sequence of this protein molecule; the sequence that is a copy thereof in that protein molecule.
b is a generically dependent continuant = Def. b is a continuant that g-depends_on one or more other entities. (axiom label in BFO2 Reference: [074-001])
(iff (GenericallyDependentContinuant a) (and (Continuant a) (exists (b t) (genericallyDependsOnAt a b t)))) // axiom label in BFO2 CLIF: [074-001]
the function of a hammer to drive in nails
the function of a heart pacemaker to regulate the beating of a heart through electricity
the function of amylase in saliva to break down starch into sugar
BFO 2 Reference: In the past, we have distinguished two varieties of function, artifactual function and biological function. These are not asserted subtypes of BFO:function however, since the same function – for example: to pump, to transport – can exist both in artifacts and in biological entities. The asserted subtypes of function that would be needed in order to yield a separate monoheirarchy are not artifactual function, biological function, etc., but rather transporting function, pumping function, etc.
A function is a disposition that exists in virtue of the bearer’s physical make-up and this physical make-up is something the bearer possesses because it came into being, either through evolution (in the case of natural biological entities) or through intentional design (in the case of artifacts), in order to realize processes of a certain sort. (axiom label in BFO2 Reference: [064-001])
(forall (x) (if (Function x) (Disposition x))) // axiom label in BFO2 CLIF: [064-001]
the boundary between the 2nd and 3rd year of your life.
p is a process boundary =Def. p is a temporal part of a process & p has no proper temporal parts. (axiom label in BFO2 Reference: [084-001])
Every process boundary occupies_temporal_region a zero-dimensional temporal region. (axiom label in BFO2 Reference: [085-002])
(forall (x) (if (ProcessBoundary x) (exists (y) (and (ZeroDimensionalTemporalRegion y) (occupiesTemporalRegion x y))))) // axiom label in BFO2 CLIF: [085-002]
(iff (ProcessBoundary a) (exists (p) (and (Process p) (temporalPartOf a p) (not (exists (b) (properTemporalPartOf b a)))))) // axiom label in BFO2 CLIF: [084-001]
the temporal region during which a process occurs.
BFO 2 Reference: A temporal interval is a special kind of one-dimensional temporal region, namely one that is self-connected (is without gaps or breaks).
A one-dimensional temporal region is a temporal region that is extended. (axiom label in BFO2 Reference: [103-001])
(forall (x) (if (OneDimensionalTemporalRegion x) (TemporalRegion x))) // axiom label in BFO2 CLIF: [103-001]
BFO 2 Reference: Material entities (continuants) can preserve their identity even while gaining and losing material parts. Continuants are contrasted with occurrents, which unfold themselves in successive temporal parts or phases [60
BFO 2 Reference: Object, Fiat Object Part and Object Aggregate are not intended to be exhaustive of Material Entity. Users are invited to propose new subcategories of Material Entity.
BFO 2 Reference: ‘Matter’ is intended to encompass both mass and energy (we will address the ontological treatment of portions of energy in a later version of BFO). A portion of matter is anything that includes elementary particles among its proper or improper parts: quarks and leptons, including electrons, as the smallest particles thus far discovered; baryons (including protons and neutrons) at a higher level of granularity; atoms and molecules at still higher levels, forming the cells, organs, organisms and other material entities studied by biologists, the portions of rock studied by geologists, the fossils studied by paleontologists, and so on.Material entities are three-dimensional entities (entities extended in three spatial dimensions), as contrasted with the processes in which they participate, which are four-dimensional entities (entities extended also along the dimension of time).According to the FMA, material entities may have immaterial entities as parts – including the entities identified below as sites; for example the interior (or ‘lumen’) of your small intestine is a part of your body. BFO 2.0 embodies a decision to follow the FMA here.
A material entity is an independent continuant that has some portion of matter as proper or improper continuant part. (axiom label in BFO2 Reference: [019-002])
Every entity which has a material entity as continuant part is a material entity. (axiom label in BFO2 Reference: [020-002])
every entity of which a material entity is continuant part is also a material entity. (axiom label in BFO2 Reference: [021-002])
(forall (x) (if (MaterialEntity x) (IndependentContinuant x))) // axiom label in BFO2 CLIF: [019-002]
(forall (x) (if (and (Entity x) (exists (y t) (and (MaterialEntity y) (continuantPartOfAt x y t)))) (MaterialEntity x))) // axiom label in BFO2 CLIF: [021-002]
(forall (x) (if (and (Entity x) (exists (y t) (and (MaterialEntity y) (continuantPartOfAt y x t)))) (MaterialEntity x))) // axiom label in BFO2 CLIF: [020-002]
b is a continuant fiat boundary = Def. b is an immaterial entity that is of zero, one or two dimensions and does not include a spatial region as part. (axiom label in BFO2 Reference: [029-001])
BFO 2 Reference: In BFO 1.1 the assumption was made that the external surface of a material entity such as a cell could be treated as if it were a boundary in the mathematical sense. The new document propounds the view that when we talk about external surfaces of material objects in this way then we are talking about something fiat. To be dealt with in a future version: fiat boundaries at different levels of granularity.More generally, the focus in discussion of boundaries in BFO 2.0 is now on fiat boundaries, which means: boundaries for which there is no assumption that they coincide with physical discontinuities. The ontology of boundaries becomes more closely allied with the ontology of regions.
BFO 2 Reference: a continuant fiat boundary is a boundary of some material entity (for example: the plane separating the Northern and Southern hemispheres; the North Pole), or it is a boundary of some immaterial entity (for example of some portion of airspace). Three basic kinds of continuant fiat boundary can be distinguished (together with various combination kinds [29
Continuant fiat boundary doesn't have a closure axiom because the subclasses don't necessarily exhaust all possibilites. An example would be the mereological sum of two-dimensional continuant fiat boundary and a one dimensional continuant fiat boundary that doesn't overlap it. The situation is analogous to temporal and spatial regions.
Every continuant fiat boundary is located at some spatial region at every time at which it exists
(iff (ContinuantFiatBoundary a) (and (ImmaterialEntity a) (exists (b) (and (or (ZeroDimensionalSpatialRegion b) (OneDimensionalSpatialRegion b) (TwoDimensionalSpatialRegion b)) (forall (t) (locatedInAt a b t)))) (not (exists (c t) (and (SpatialRegion c) (continuantPartOfAt c a t)))))) // axiom label in BFO2 CLIF: [029-001]
BFO 2 Reference: Immaterial entities are divided into two subgroups:boundaries and sites, which bound, or are demarcated in relation, to material entities, and which can thus change location, shape and size and as their material hosts move or change shape or size (for example: your nasal passage; the hold of a ship; the boundary of Wales (which moves with the rotation of the Earth) [38, 7, 10
the line separating the outer surface of the mucosa of the lower lip from the outer surface of the skin of the chin.
a one-dimensional continuant fiat boundary is a continuous fiat line whose location is defined in relation to some material entity. (axiom label in BFO2 Reference: [032-001])
(iff (OneDimensionalContinuantFiatBoundary a) (and (ContinuantFiatBoundary a) (exists (b) (and (OneDimensionalSpatialRegion b) (forall (t) (locatedInAt a b t)))))) // axiom label in BFO2 CLIF: [032-001]
one-dimensional continuant fiat boundary
On a somewhat higher level of complexity are what we shall call rate process profiles, which are the targets of selective abstraction focused not on determinate quality magnitudes plotted over time, but rather on certain ratios between these magnitudes and elapsed times. A speed process profile, for example, is represented by a graph plotting against time the ratio of distance covered per unit of time. Since rates may change, and since such changes, too, may have rates of change, we have to deal here with a hierarchy of process profile universals at successive levels
One important sub-family of rate process profiles is illustrated by the beat or frequency profiles of cyclical processes, illustrated by the 60 beats per minute beating process of John’s heart, or the 120 beats per minute drumming process involved in one of John’s performances in a rock band, and so on. Each such process includes what we shall call a beat process profile instance as part, a subtype of rate process profile in which the salient ratio is not distance covered but rather number of beat cycles per unit of time. Each beat process profile instance instantiates the determinable universal beat process profile. But it also instantiates multiple more specialized universals at lower levels of generality, selected from rate process profilebeat process profileregular beat process profile3 bpm beat process profile4 bpm beat process profileirregular beat process profileincreasing beat process profileand so on.In the case of a regular beat process profile, a rate can be assigned in the simplest possible fashion by dividing the number of cycles by the length of the temporal region occupied by the beating process profile as a whole. Irregular process profiles of this sort, for example as identified in the clinic, or in the readings on an aircraft instrument panel, are often of diagnostic significance.
The simplest type of process profiles are what we shall call ‘quality process profiles’, which are the process profiles which serve as the foci of the sort of selective abstraction that is involved when measurements are made of changes in single qualities, as illustrated, for example, by process profiles of mass, temperature, aortic pressure, and so on.
b is a process_profile =Def. there is some process c such that b process_profile_of c (axiom label in BFO2 Reference: [093-002])
b process_profile_of c holds when b proper_occurrent_part_of c& there is some proper_occurrent_part d of c which has no parts in common with b & is mutually dependent on b& is such that b, c and d occupy the same temporal region (axiom label in BFO2 Reference: [094-005])
(forall (x y) (if (processProfileOf x y) (and (properContinuantPartOf x y) (exists (z t) (and (properOccurrentPartOf z y) (TemporalRegion t) (occupiesSpatioTemporalRegion x t) (occupiesSpatioTemporalRegion y t) (occupiesSpatioTemporalRegion z t) (not (exists (w) (and (occurrentPartOf w x) (occurrentPartOf w z))))))))) // axiom label in BFO2 CLIF: [094-005]
(iff (ProcessProfile a) (exists (b) (and (Process b) (processProfileOf a b)))) // axiom label in BFO2 CLIF: [093-002]
a marriage bond, an instance of love, an obligation between one person and another.
b is a relational quality = Def. for some independent continuants c, d and for some time t: b quality_of c at t & b quality_of d at t. (axiom label in BFO2 Reference: [057-001])
(iff (RelationalQuality a) (exists (b c t) (and (IndependentContinuant b) (IndependentContinuant c) (qualityOfAt a b t) (qualityOfAt a c t)))) // axiom label in BFO2 CLIF: [057-001]
a two-dimensional continuant fiat boundary (surface) is a self-connected fiat surface whose location is defined in relation to some material entity. (axiom label in BFO2 Reference: [033-001])
(iff (TwoDimensionalContinuantFiatBoundary a) (and (ContinuantFiatBoundary a) (exists (b) (and (TwoDimensionalSpatialRegion b) (forall (t) (locatedInAt a b t)))))) // axiom label in BFO2 CLIF: [033-001]
two-dimensional continuant fiat boundary
the point of origin of some spatial coordinate system.
the quadripoint where the boundaries of Colorado, Utah, New Mexico, and Arizona meet
zero dimension continuant fiat boundaries are not spatial points. Considering the example 'the quadripoint where the boundaries of Colorado, Utah, New Mexico, and Arizona meet' : There are many frames in which that point is zooming through many points in space. Whereas, no matter what the frame, the quadripoint is always in the same relation to the boundaries of Colorado, Utah, New Mexico, and Arizona.
a zero-dimensional continuant fiat boundary is a fiat point whose location is defined in relation to some material entity. (axiom label in BFO2 Reference: [031-001])
(iff (ZeroDimensionalContinuantFiatBoundary a) (and (ContinuantFiatBoundary a) (exists (b) (and (ZeroDimensionalSpatialRegion b) (forall (t) (locatedInAt a b t)))))) // axiom label in BFO2 CLIF: [031-001]
zero-dimensional continuant fiat boundary
a temporal region that is occupied by a process boundary
the moment at which a finger is detached in an industrial accident
A zero-dimensional temporal region is a temporal region that is without extent. (axiom label in BFO2 Reference: [102-001])
(forall (x) (if (ZeroDimensionalTemporalRegion x) (TemporalRegion x))) // axiom label in BFO2 CLIF: [102-001]
A triazole-based antifungal agent used for the treatment of esophageal candidiasis, invasive pulmonary aspergillosis, and serious fungal infections caused by Scedosporium apiospermum and Fusarium spp. It is an inhibitor of cytochrome P450 2C9 (CYP2C9) and CYP3A4.
A quinolone that is quinolin-4(1H)-one bearing cyclopropyl, carboxylic acid, fluoro and piperazin-1-yl substituents at positions 1, 3, 6 and 7, respectively.
1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid
1-CYCLOPROPYL-6-FLUORO-4-OXO-7-PIPERAZIN-1-YL-1,4-DIHYDROQUINOLINE-3-CARBOXYLIC ACID
1-Cyclopropyl-6-fluoro-4-oxo-7-piperazin-1-yl-1,4-dihydro-quinoline-3-carboxylic acid
1-Cyclopropyl-6-fluoro-7-(4-methyl-piperazin-1-yl)-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid
1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid
1-cyclopropyl-6-fluoro-4-oxo-7-piperazin-1-ylquinoline-3-carboxylic acid
1-cyclopropyl-6-fluoro-7-hexahydro-1-pyrazinyl-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid
cyclopentyl 3-[2-methoxy-4-(2-methylphenylsulfonylcarbamoyl)benzyl]-1-methyl-1H-indol-5-ylcarbamate
cyclopentyl 3-(2-methoxy-4-((o-tolylsulfonyl)carbamoyl)benzyl)-1-methylindole-5-carbamate
A pyrimidine 2',3'-dideoxyribonucleoside compound having a 3'-azido substituent and thymine as the nucleobase.
A member of the class of 1-benzothiophenes that is 1-benzothiophene in which the hydrogen at position 2 is replaced by a 1-[carbamoyl(hydroxy)amino]ethyl group. A selective 5-lipoxygenase inhibitor, it inhibits the formation of leukotrienes LTB4, LTC4, LDT4, and LTE4. It is used for the management of chronic asthma.
A 5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepin-3-yl acetate in which both stereocentres have S configuration. A calcium-channel blocker and vasodilator, it is used as the hydrochloride in the management of angina pectoris and hypertension.
(2S,3S)-5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepin-3-yl acetate
(+)-cis-5-[2-(dimethylamino)ethyl]-2,3-dihydro-3-hydroxy-2-(p-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one acetate ester
(2S,3S)-5-(2-(dimethylamino)ethyl)-2-(4-methoxyphenyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-3-yl acetate
Acetic acid (2S,3S)-5-(2-dimethylamino-ethyl)-2-(4-methoxy-phenyl)-4-oxo-2,3,4,5-tetrahydro-benzo[b][1,4]thiazepin-3-yl ester
A quinazoline compound having a (3-ethynylphenyl)amino group at the 4-position and two 2-methoxyethoxy groups at the 6- and 7-positions.
An N-methylated tetrahydroisoquinoline carrying phenyl and amino substituents at positions C-4 and C-8, respectively.
1,4-Dihydro-2H-3,1-benzoxazin-2-one substituted at the 4 position by cyclopropylethynyl and trifluoromethyl groups (S configuration) and at the 6 position by chlorine. A non-nucleoside reverse transcriptase inhibitor with activity against HIV, it is used with other antiretrovirals for combination therapy of HIV infection.
A secondary amino compound having methyl and 3-(2-methylphenoxy)-3-phenylpropan-1-yl substituents.
A member of the class of lysophosphatidic acids obtained by hydrolytic removal of one of the two acyl groups of any phosphatidic acid. A 'closed' class.
PMID:20118541 Lysophosphatidic acid (LPA) is a lipid mediator that is known to exhibit chemotactic activity toward a variety of cancer cells. However, its effect on the immune system has not been studied extensively. Another lipid mediator, sphingosine-1-phosphate (S1P), has been shown to influence lymphocyte recirculation by regulating lymphocyte egress from lymphoid organs. In this study, we found that LPA inhibits spontaneous migration of mouse splenic lymphocytes through a chemorepulsive effect. We also demonstrated that LPA inhibits chemokine CCL21-induced lymphocyte migration. This inhibitory effect on CCL21-induced migration was observed for both T and B cells. The involvement of a receptor, LPA(1), LPA(2) or LPA(3), in the inhibition of the CCL21-induced migration was confirmed with a synthetic agonist, oleyl thiophosphate. Considering that the signaling by CCL21 through cognate receptor CCR7 contributes to lymphocyte homing and dendritic cell trafficking to lymph nodes, LPA may play a role as a key regulator of these processes. The inhibitory effect of LPA is in remarkable contrast to the effect of S1P receptor signaling, which is known to potentiate lymphocyte chemotaxis involving CCR7.
PMID:7768880 Lysophosphatidic acid, a multifunctional phospholipid messenger. Lysophosphatidic acid (LPA1(1); 1-acyl-glycerol-3-phosphate),is the simplest of all glycerophospholipids. While LPA has long been known as a precursor of phospholipid biosynthesis in both eukaryotic and prokaryotic cells, only recently has LPA emerged as an intercellular signaling molecule that is rapidly produced and released by activated cells, notably platelets, to influence target cells by acting on a specific cell-surface receptor. The list of biological responses to LPA is quite diverse, ranging from induction of cell proliferation to stimulation of neurite retraction. The mitogenic activities of LPA have been best studied in fibroblasts. As with peptide growth factors, induction of DNA synthesis by LPA requires its long term presence in the medium LPA, but not peptide growth factors, can mimic serum in inducing invasion of carcinoma and hepatoma cells into monolayers of mesothelial cells. The underlying mechanism is not clear but may well involve both increased cell adhesion and enhanced cell motility. Many mitogens activate the p85/p110 phosphatidylinositol (PI) 3-kinase in their target cells and so does LPA. LPA-induced PI 3-kinase activity has been found in 3T3 cells (Ref. 44; but see ref. 45 for conflicting data) and in megakaryoblastic cells. Whatever its precise link to the LPA receptor and physiological function, PI 3-kinase does not seem to be essential for mitogenic signaling, since microinjection of a neutralizing antibody does not affect LPA-induced DNA synthesis.
A class of lipoproteins with a density between that of low-density and very-low-density lipoproteins. They are formed by the degradatiion of very-low-density lipoproteins.
An agonist that binds to and activates farnesoid X receptors
A drug that makes increases the sensitivity of tumour cells to radiation therapy.
A role played by the entity which inhibits the oxidation of any fatty acid.
Abbreviation for nicotinamide-adenine dinucleotide when its oxidation state is unknown or unspecified. It is used in metabolic pathways like glycolysis and citric acid cycle.
Pirprofen was a nonsteroidal anti-inflammatory drug (NSAID) that was brought to market by Ciba-Geigy in 1982 as a treatment for arthritis and pain. (by Wikipedia)
Alpidem (Ananxyl) is an anxiolytic drug from the imidazopyridine family, related to the more well known sleeping medication zolpidem. (by Wikipedia)
Any psychotropic drug that induces anxiety or panic.
Any pathway inhibitor that inhibits the Hedgehog signalling pathway.
A chloroalkane that is propane in which a hydrogen from each of two adjacent carbons has been replaced by chlorines.
A monounsaturated fatty aldehyde that is nonanal that has undergone dehydrogenation to introduce a double bond at any position in the aliphatic chain and in which a hydrogen at position 4 has been replaced by a hydroxy group.
Tetracycline in which the hydroxy group at position 5 and the methyl group at position 6 are replaced by hydrogen, and with a dimethylamino substituent and an (N-tert-butylglycyl)amino substituent at positions 7 and 9, respectively. A glycylcycline antibiotic, it has activity against a broad range of Gram-positive and Gram-negative bacteria, including tetracycline-resistant organisms. It is used for the intravenous treatment of complicated skin and skin structure infections caused by susceptible organisms.
The aldehyde formed from acetic acid by reduction of the carboxy group. It is the most abundant carcinogen in tobacco smoke.
An adenosine 5'-phosphate in which the 5'-phosphate is a triphosphate group. It is involved in the transportation of chemical energy during metabolic pathways.
The oxidised form of nicotinamide adenine dinucleotide found in all living cells. In metabolism, NAD(+) is involved in redox reactions, carrying electrons from one reaction to another.
A nucleobase-containing molecular entity with a polymeric structure comprised of a linear sequence of 13 or more nucleotide residues.
A class of glycerophospholipids in which a phosphatidyl group is esterified to the hydroxy group of ethanolamine.
A cholestanoid consisting of cholestane having a double bond at the 5,6-position as well as a 3β-hydroxy group.
1-O-(3-sn-phosphatidyl)-1D-myo-inositol 3,4-bis(dihydrogen phosphate)
1-Phosphatidyl-1D-myo-inositol 3,4-bisphosphate
A primary alcohol that is ethane in which one of the hydrogens is substituted by a hydroxy group.
A lipid containing phosphoric acid as a mono- or di-ester. The term encompasses phosphatidic acids and phosphoglycerides.
A monohydroxy-5β-cholanic acid with aα-hydroxy substituent at position 3. It is a bile acid obtained from chenodeoxycholic acid by bacterial action.
A ribonucleoside composed of a molecule of adenine attached to a ribofuranose moiety via a beta-N(9)-glycosidic bond.
A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.
A derivative of glycerol in which one hydroxy group, commonly but not necessarily primary, is esterified with phosphoric acid and the other two are esterified with fatty acids.
A bile acid that is 5β-cholan-24-oic acid bearing threeα-hydroxy substituents at position 3, 7 and 12.
A sphing-4-enine in which the double bond is trans.
Liposaccharide natural compounds consisting of a trisaccharide repeating unit (two heptose units and octulosonic acid) with oligosaccharide side chains and 3-hydroxytetradecanoic acid units (they are a major constituent of the cell walls of Gram-negative bacteria).
Lipopolysaccharide (LPS) is a glycosylated lipid on the outer surface of Gram-negative bacteria acts as immunostimulants.
NADPH is the reduced form of NADP+; used in anabolic reactions, such as lipid and nucleic acid synthesis, which require NADPH as a reducing agent.
2'-O-phosphonoadenosine 5'-{3-[1-(3-carbamoyl-1,4-dihydropyridin-1-yl)-1,4-anhydro-D-ribitol-5-yl] dihydrogen diphosphate}
A nitrogen oxide which is a free radical, each molecule of which consists of one nitrogen and one oxygen atom.
A member of the class of chloroethenes that is ethene substituted by chloro groups at positions 1, 1 and 2.
1-O-(3-sn-phosphatidyl)-1D-myo-inositol 3,4,5-tris(dihydrogen phosphate)
1-Phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
Any member of the class of organooxygen compounds that is a polyhydroxy-aldehyde or -ketone or a lactol resulting from their intramolecular condensation (monosaccharides); substances derived from these by reduction of the carbonyl group (alditols), by oxidation of one or more hydroxy groups to afford the corresponding aldehydes, ketones, or carboxylic acids, or by replacement of one or more hydroxy group(s) by a hydrogen atom; and polymeric products arising by intermolecular acetal formation between two or more such molecules (disaccharides, polysaccharides and oligosaccharides). Carbohydrates contain only carbon, hydrogen and oxygen atoms; prior to any oxidation or reduction, most have the empirical formula Cm(H2O)n. Compounds obtained from carbohydrates by substitution, etc., are known as carbohydrate derivatives and may contain other elements. Cyclitols are generally not regarded as carbohydrates.
A carbamate ester that is methyl 1H-benzimidazol-2-ylcarbamate substituted by a propylsulfanyl group at position 5. It is commonly used in the treatment of parasitic worm infestations.
methyl [5-(propylsulfanyl)-1H-benzimidazol-2-yl]carbamate
(5-(propylthio)-1H-benzimidazol-2-yl)carbamic acid methyl ester
O-methyl N-(5-(propylthio)-2-benzimidazolyl)carbamate
Amide derived from two or more amino carboxylic acid molecules (the same or different) by formation of a covalent bond from the carbonyl carbon of one to the nitrogen atom of another with formal loss of water. The term is usually applied to structures formed from alpha-amino acids, but it includes those derived from any amino carboxylic acid. X = OH, OR, NH2, NHR, etc.
A phosphatidylinositol in which the inositol moiety is the 1D-myo isomer and the phosphatidyl group is located at its position 1.
A purine nucleoside in which guanine is attached to ribofuranose via a beta-N(9)-glycosidic bond.
A dihydroxy-5beta-cholanic acid that is (5beta)-cholan-24-oic acid substituted by hydroxy groups at positions 3 and 7 respectively.
A dihydroxy-5β-cholanic acid that is (5β)-cholan-24-oic acid substituted by hydroxy groups at positions 3 and 7 respectively.
3alpha,7alpha-dihydroxy-5beta-cholan-24-oic acid
3alpha,7alpha-Dihydroxy-5beta-cholanic acid
A purine ribonucleoside 5'-diphosphate having adenine as the nucleobase.
A tripeptide compound consisting of glutamic acid attached via its side chain to the N-terminus of cysteinylglycine.
A coenzyme found in all living cells; consists of two nucleotides joined through their 5'-phosphate groups, with one nucleotide containing an adenine base and the other containing nicotinamide.
A monohydroxybenzoic acid that is benzoic acid with a hydroxy group at the ortho position. It is obtained from the bark of the white willow and wintergreen leaves.
Derivatives of phosphoglycerols which have only one of the alcohol groups of the glycerol backbone ester-linked with a fatty acid.
A member of the class of biladienes that is a linear tetrapyrrole with the dipyrrole units being of both exovinyl and endovinyl type. A product of heme degradation, it is produced in the reticuloendothelial system by the reduction of biliverdin and transported to the liver as a complex with serum albumin.
High molecular weight, linear polymers, composed of nucleotides containing deoxyribose and linked by phosphodiester bonds; DNA contain the genetic information of organisms.
An aldohexose used as a source of energy and metabolic intermediate.
An androstanoid having 17beta-hydroxy and 3-oxo groups, together with unsaturation at C-4-C-5..
The parent of the class of 2-acetamidofluorenes, being an ortho-fused polycyclic arene that consists of 9H-fluorene bearing an acetamido substituent at position 2. It is a carcinogenic and mutagenic derivative of fluorene.
A cytidine 5'-phosphate that has formula C9H14N3O8P.
A compound RC(2O)H, in which a carbonyl group is bonded to one hydrogen atom and to one R group.
A glycerophosphoglycerol that is glycerol in which the hydrogen of one of the primary hydroxy groups has been replaced by a phosphatidyl group.
A 2'-deoxycytidine having geminal fluoro substituents in the 2'-position. An inhibitor of ribonucleotide reductase, gemcitabine is used in the treatment of various carcinomas, particularly non-small cell lung cancer, pancreatic cancer, bladder cancer and breast cancer.
cytidine 5'-(tetrahydrogen triphosphate)
A phthalate ester that is the bis(2-ethylhexyl) ester of benzene-1,2-dicarboxylic acid.
Ceramides (N-acyl-sphingoid bases) are a major subclass of sphingoid base derivatives with an amide-linked fatty acid. The fatty acids are typically saturated or monounsaturated with chain lengths from 14 to 26 carbon atoms; the presence of a hydroxyl group on carbon 2 is fairly common. Ceramides are generally precursors of more complex sphingolipids. In the illustrated generalised structure, R(1) = OH, OX (where X = acyl, glycosyl, phosphate, phosphonate, etc.), or H.
Gentamicin is a parenterally administered, broad spectrum aminoglycoside antibiotic typically used for moderate to severe gram negative infections. Despite its wide use, gentamicin has not been definitively linked to instances of clinically apparent liver injury.
Any glyceride resulting from the condensation of all three hydroxy groups of glycerol (propane-1,2,3-triol) with fatty acids.
An epoxide that is oxirane in which one of the hydrogens has been replaced by a phenyl group.
A thioester that results from the formal condensation of the thiol group of coenzyme A with the carboxy group of any carboxylic acid.
'Lipids' is a loosely defined term for substances of biological origin that are soluble in nonpolar solvents. They consist of saponifiable lipids, such as glycerides (fats and oils) and phospholipids, as well as nonsaponifiable lipids, principally steroids.
Organic molecule that is insoluble in water but tends to dissolve in nonpolar organic solvent.
A biomacromolecule consisting of large numbers of monosaccharide residues linked glycosidically. This term is commonly used only for those containing more than ten monosaccharide residues.
Any phosphatidylinositol that is phosphorylated at one or more of the hydroxy groups of inositol.
An iron group element atom that has atomic number 26.
A class of aminophospholipids in which a phosphatidyl group is esterified to the hydroxy group of serine.
The threo-diastereomer of 1,4-dimercaptobutane-2,3-diol.
PI(4,5)P2 is cleaved by phospholipase C-beta or gamma to generate IP3 and diacylglycerol.
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
A mitochondrial respiratory-chain inhibitor that interferes with the action of ATP synthase.
ATP synthase inhibitor (mitochondrial respiratory-chain inhibitor)
Any of a group of related and highly toxic secondary metabolites (mycotoxins) whose main structural feature is a fused coumarin-bis(dihydrofuran) ring system and which are produced by strains of the moulds Aspergillus flavus or A. parasiticus, together with further metabolites of these mycotoxins.
Highly reactive chemical that introduces alkyl radicals into biologically active molecules and thereby prevents their proper functioning. It could be used as an antineoplastic agent, but it might be very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. It could also be used as a component of poison gases.
A monoatomic or polyatomic species having one or more elementary charges of the electron.
A role that opposes oxidation or inhibits reactions brought about by dioxygen or peroxides.
A substance that opposes oxidation or inhibits reactions brought about by dioxygen or peroxides.
A substance that destroys or inhibits replication of viruses.
Members of the class of pyrimidones consisting of pyrimidine-2,4,6(1H,3H,5H)-trione (barbituric acid) and its derivatives. Largest group of the synthetic sedative/hypnotics, sharing a characteristic six-membered ring structure.
A molecular entity having an available pair of electrons capable of forming a covalent bond with a hydron (Bronsted base) or with the vacant orbital of some other molecular entity (Lewis base).
An EC 4.2.1.* (hydro-lyases) inhibitor that interferes with the action of carbonic anhydrase (EC 4.2.1.1). Such compounds reduce the secretion of H(+) ions by the proximal kidney tubule.
EC 4.2.1.1 (carbonic anhydrase) inhibitors
carbonate hydro-lyase (carbon-dioxide-forming) inhibitor
carbonate hydro-lyase (carbon-dioxide-forming) inhibitors
carbonic anhydrase (EC 4.2.1.1) inhibitor
carbonic anhydrase (EC 4.2.1.1) inhibitors
EC 4.2.1.1 (carbonic anhydrase) inhibitor
A substance intended to sterilize any organism.
A low-molecular-weight, non-protein organic compound participating in enzymatic reactions as dissociable acceptor or donor of chemical groups or electrons.
An organic molecule or ion (usually a metal ion) that is required by an enzyme for its activity. It may be attached either loosely (coenzyme) or tightly (prosthetic group).
Any constitutionally or isotopically distinct atom, molecule, ion, ion pair, radical, radical ion, complex, conformer etc., identifiable as a separately distinguishable entity.
A tetrasaccharide derivative consisting of a dideoxy-4-{[4,5,6-trihydroxy-3-(hydroxymethyl)cyclohex-2-en-1-yl C7 cyclitol moiety [called valienol (or valienamine)] linked via nitrogen to isomaltotriose.
Any substance which when absorbed into a living organism may modify one or more of its functions. The term is generally accepted for a substance taken for a therapeutic purpose, but is also commonly used for abused substances.
Intended use of the molecular entity or part thereof by humans.
Any member of the group of signalling molecules arising from oxidation of the three C20 essential fatty acids (EFAs) icosapentaenoic acid (EPA), arachidonic acid (AA) and dihomo-gamma-linolenic acid (DGLA).
A compound or agent that combines with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
A 3-hydroxy steroid that is estra-1,3,5(10)-triene substituted by hydroxy groups at positions 3 and 17.
A member of the class of N-nitrosoureas that is urea in which one of the nitrogens is substituted by ethyl and nitroso groups.
Amfenac in which the the hydrogen at the 4 position of the benzoyl group is substituted by bromine. It is used for the management of ocular pain and treatment of postoperative inflammation in patients who have undergone cataract extraction. It was withdrawn from the US market in 1998, following concerns over off-label abuse and hepatic failure.
[2-amino-3-(4-bromobenzoyl)phenyl]acetic acid
2-amino-3-(4-bromobenzoyl)benzeneacetic acid
[2-Amino-3-(4-bromo-benzoyl)-phenyl]-acetic acid
A substance used to destroy fungal pests.
A chemical entity is a physical entity of interest in chemistry including molecular entities, parts thereof, and chemical substances.
A role played by the molecular entity or part thereof within a biological context.
Originally referring to an endogenous compound that is formed in specialized organ or group of cells and carried to another organ or group of cells, in the same organism, upon which it has a specific regulatory function, the term is now commonly used to include non-endogenous, semi-synthetic and fully synthetic analogues of such compounds.
substance with hormone role: http://purl.bioontology.org/ontology/STY/T125
Nuclear particle of charge number +1, spin 1/2 and rest mass of 1.007276470(12) u.
Compounds having the structure RN=CR2 (R = H, hydrocarbyl). Thus analogues of aldehydes or ketones, having NR doubly bonded to carbon; aldimines have the structure RCH=NR, ketimines have the structure R'2C=NR (where R' is not H). Imines include azomethines and Schiff bases. Imine is used as a suffix in systematic nomenclature to denote the C=NH group excluding the carbon atom.
Strictly, a substance intended to kill members of the class Insecta. In common usage, any substance used for preventing, destroying, repelling or controlling insects.
A molecular entity having a net electric charge.
An aflatoxin having a tetrahydrocyclopenta[c]furo[3',2':4,5]furo[2,3-h]chromene skeleton with oxygen functionality at positions 1, 4 and 11.
Any intermediate or product resulting from metabolism. The term 'metabolite' subsumes the classes commonly known as primary and secondary metabolites.
A role played by the entity that inhibits the mitochondrial respiratory-chain.
mitochondrial electron transport chain inhibitors
mitochondrial respiratory-chain inhibitor
Any polyatomic entity that is an electrically neutral entity consisting of more than one atom.
An agent that increases the frequency of mutations above the normal background level, usually by interacting directly with DNA and causing it damage, including base substitution.
A tetraphene having methyl substituents at the 7- and 12-positions. It is a potent carcinogen and is present in tobacco smoke.
A substance used to destroy pests of the phylum Nematoda (roundworms).
An endogenous compound that is used to transmit information across the synapse between a neuron and another cell.
An organophosphorus compound is formally a compound containing at least one carbon-phosphorus bond, but the term is often extended to include esters and thioesters.
Strictly, a substance intended to kill pests. In common usage, any substance used for controlling, preventing, or destroying animal, microbiological or plant pests.
The family of natural prostaglandins and prostaglandin-like compounds.
A molecular entity possessing an unpaired electron.
Molecules or ions formed by the incomplete one-electron reduction of oxygen. They contribute to the microbicidal activity of phagocytes, regulation of signal transduction and gene expression, and the oxidative damage to biopolymers.
Any fatty acid containing no carbon to carbon multiple bonds. Known to produce adverse biological effects when ingested to excess.
A member of the class of 1-benzofurans that is 1-benzofuran substituted by a butyl group at position 2 and a 4-[2-(diethylamino)ethoxy]-3,5-diiodobenzoyl group at position 3. It is a cardiovascular drug used for the treatment of cardiac dysrhythmias.
2-Butyl-3-benzofuranyl 4-(2-(diethylamino)ethoxy)-3,5-diiodophenyl ketone
An organic tricyclic compound that is 10,11-dihydro-5H-dibenzo[a,d][7]annulene substituted by a 3-(dimethylamino)propylidene group at position 5.
Sphingolipids are a complex family of compounds that share a common structural feature, a sphingoid base backbone.
A class of oxygenated oxane derivatives, originally derived from prostaglandin precursors in platelets, that stimulate aggregation of platelets and constriction of blood vessels.
Poisonous substance produced by a biological organism such as a microbe, animal or plant.
A chemical compound containing three hydroxy groups.
An oxopurine that is the final oxidation product of purine metabolism.
A chlorocarbon that is methane in which all the hydrogens have been replaced by chloro groups.
An oxaspiro compound produced by Penicillium griseofulvum. It is used by mouth as an antifungal drug for infections involving the scalp, hair, nails and skin that do not respond to topical treatment.
A stilbenol that is stilbene in which the phenyl groups are substituted at positions 3, 5, and 4' by hydroxy groups.
A broad-spectrum polyketide antibiotic produced by the Streptomyces genus of actinobacteria.
A member of the class of rifamycins that is a a semisynthetic antibiotic derived from Amycolatopsis rifamycinica (previously known as Amycolatopsis mediterranei and Streptomyces mediterranei)
A polydisperse, highly branched glucan composed of chains of D-glucopyranose residues in alpha(1->4) glycosidic linkage, joined together by alpha(1->6) glycosidic linkages. A small number of alpha(1->3) glycosidic linkages and some cumulative alpha(1->6) links also may occur. The branches in glycogen typically contain 8 to 12 glucose residues.
A benzylisoquinoline alkaloid that is isoquinoline substituted by methoxy groups at positions 6 and 7 and a 3,4-dimethoxybenzyl group at position 1. It has been isolated from Papaver somniferum.
A monocarboxylic acid that is phenanthrene-1-carboxylic acid that is substituted by a methylenedioxy group at the 3,4 positions, by a methoxy group at position 8, and by a nitro group at position 10. It is the most abundant of the aristolochic acids and is found in almost all Aristolochia (birthworts or pipevines) species. It has been tried in a number of treatments for inflammatory disorders, mainly in Chinese and folk medicine. However, there is concern over their use as aristolochic acid is both carcinogenic and nephrotoxic.
8-methoxy-6-nitrophenanthro[3,4-d][1,3]dioxole-5-carboxylic acid
A phosphatidylglycerol composed of two molecules of phosphatidic acid covalently linked to a molecule of glycerol.
A monohaloethene that is ethene in which one of the hydrogens has been replaced by a chloro group.
A pyrimidine nucleoside in which cytosine is attached to D-arabinofuranose via a beta-N(1)-glycosidic bond. Used mainly in the treatment of leukaemia, especially acute non-lymphoblastic leukaemia, cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. It also has antiviral and immunosuppressant properties.
A ketohexose that is an isomer of glucose.
Any member of the phosphoinositide family of compounds, of which seven occur naturally.
A chromenone having the keto group located at the 2-position.
A bile acid that is 5β-cholan-24-oic acid substituted by hydroxy groups at positions 3 and 12 respectively.
Any glycerophosphoinositol having one phosphatidyl group esterified to one of the hydroxy groups of inositol.
A methanesulfonate ester that is butane-1,4-diol in which the hydrogens of the hydroxy groups are replaced by methanesulfonyl groups. An alkylating antineoplastic agent, it is used for the treatment of chronic myeloid leukemia (although it has been largely replaced by newer drugs). It is also used as an insect sterilant.
A thiopurine that is 6-mercaptopurine in which the mercapto hydrogen is replaced by a 1-methyl-4-nitroimidazol-5-yl group. It is a prodrug for mercaptopurine and is used as an immunosuppressant, prescribed for the treatment of inflammatory conditions and after organ transplantation and also for treatment of Crohn's didease and MS.
(3aS,4R,7S,9R,10R,11R,13R,15R,15aR)-4-ethyl-11-methoxy-3a,7,9,11,13,15-hexamethyl-2,6,8,14-tetraoxo-1-[4-(4-pyridin-3-yl-1H-imidazol-1-yl)butyl]tetradecahydro-2H-oxacyclotetradecino[4,3-d][1,3]oxazol-10-yl 3,4,6-trideoxy-3-(dimethylamino)-beta-D-xylo-hexopyranoside
A mixture of antiviral nucleoside antibiotics produced by Streptomyces lysosuperificus. It contains at least 10 homologues comprising uracil, N-acetylglucosamine, an 11-carbon aminodialdose called tunicamine, and a fatty acid linked to the amino group of the tunicamine. The homologues vary in the composition of the fatty acid moiety.
1-Benzofuran substituted at C-2 and C-3 by an ethyl group and a 3,5-dibromo-4-hydroxybenzoyl group respectively. An inhibitor of CYP2C9, it is used as an anti-gout medication.
3,5-dibromo-4-hydroxyphenyl-2-ethyl-3-benzofuranyl ketone
A compound in which a hydroxy group, -OH, is attached to a saturated carbon atom.
A racemate comprising of equal amounts of (R)-bicalutamide and (S)-bicalutamide. It is an oral non-steroidal antiandrogen used in the treatment of prostate cancer and hirsutism.
A monocarboxylic acid that is acetic acid in which all three methyl hydrogens are substituted by chlorine.
An aromatic ether in which the ether oxygen links an allyl group to the 4-position of (3-chlorophenyl)acetic acid.A non-steroidal anti-inflammatory drug, it was withdrawn from the UK market in 1979 due to concerns with its association with vasculitis and rash.
[3-chloro-4-(prop-2-en-1-yloxy)phenyl]acetic acid
3-Chloro-4-(2-propenyloxy)benzeneacetic acid
[4-(allyloxy)-3-chlorophenyl]acetic acid
A monocarboxylic acid that is glycolic acid in which the hydrogen attached to the 2-hydroxy group is replaced by a 1-benzyl-1H-indazol-3-yl group. Although it has anti-inflammatory, antinecrotic, choleretic and antilipidaemic properties and has been used for the treatment of various inflammatory skin disorders, its principal effect is to inhibit the denaturation of proteins. Its lysine salt is used in the management of cataracts.
[(1-benzyl-1H-indazol-3-yl)oxy]acetic acid
A 1,3-thiazolemonocarboxylic acid that is 4-methyl-1,3-thiazole-5-carboxylic acid which is substituted by a 3-cyano-4-(2-methylpropoxy)phenyl group at position 2. It is an orally-active, potent, and selective xanthine oxidase inhibitor used for the treatment of chronic hyperuricaemia in patients with gout.
2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methyl-1,3-thiazole-5-carboxylic acid
2-(3-cyano-4-isobutoxyphenyl)-4-methyl-1,3-thiazole-5-carboxylic acid
A carboxylic ester that is 2,3-dihydroxypropyl anthranilate in which the amino group is substituted by a 7-chloroquinolin-4-yl group. A non-steroidal anti-inflammatory drug, glafenine and its hydrochloride salt were used for the relief of all types of pain, but high incidence of anaphylactic reactions resulted in their withdrawal from the market.
2,3-dihydroxypropyl 2-[(7-chloroquinolin-4-yl)amino]benzoate
2,3-Dihydroxypropyl N-(7-chloro-4-quinolyl) anthranilate
4-((2-Carboxyphenyl)amino)-7-chloroquinoline alpha-monoglyceride
A dicarboxylic acid amide in which a parent structure of amphetamine is substituted on nitrogen by a (2,6-dimethylphenoxy)acetyl group and on the carbon alpha to nitrogen by a (1S,3S)-1-hydroxy-3-{[(2S)-3-methyl-2-(2-oxotetrahydropyrimidin-1(2H)-yl)butanoyl]amino}-4-phenylbutyl group. An antiretroviral of the protease inhibitor class. It is used against HIV infections as a fixed-dose combination with another protease inhibitor, ritonavir.
The simplest member of the class of bromobenzenes, that is benzene in which a single hydrogen has been substituted by a bromine. A liquid at room temperature (m.p. -30degreeC; b.p.760 156degreeC), it is used as a solvent, particularly for large-scale crystallisations, and for the introduction of phenyl groups in organic synthesis.
A platinum coordination entity that is a commonly used chemothrepeutic drug for treatment of colorectal cancer.
A morphinane alkaloid that is 7,8-dihydromorphine 6-O-methyl ether in which positions 6 and 14 are joined by a -CH2CH2- bridge, one of the hydrogens of the N-methyl group is substituted by cyclopropyl, and a hydrogen at position 7 is substituted by a 2-hydroxy-3,3-dimethylbutan-2-yl group.
A carbocyclic fatty acid that is 5-aminoheptanoic acid in which one of the hydrogens attached to the nitrogen is replaced by a 10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-yl group. A tricyclic antidepressant, it was never approved in the US and was withdrawn from the French market in 1999 due to concerns over abuse, dependence and severe acne.
7-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylamino)heptanoic acid
({4-chloro-6-[(2,3-dimethylphenyl)amino]pyrimidin-2-yl}sulfanyl)acetic acid
Any monoacylglycerol phosphate obtained by hydrolytic removal of one of the two acyl groups of any phosphatidic acid or derivatives therein.
A fatty acyl-CoA that results from the formal condensation of the thiol group of coenzyme A with the carboxy group of any long-chain (C13 to C22) fatty acid.
A substance that kills or slows the growth of Mycobacterium tuberculosis and is used in the treatment of tuberculosis.
A chemical entity constituting the smallest component of an element having the chemical properties of the element.
A substance that kills or slows the growth of microorganisms, including bacteria, viruses, fungi and protozoans.
A substance (or active part thereof) that kills or slows the growth of bacteria.
A substance that kills or slows the growth of bacteria.
Any material that can be ingested by an organism.
A macromolecule formed by a living organism.
A macromolecule made up of nucleotide units and hydrolysable into certain pyrimidine or purine bases (usually adenine, cytosine, guanine, thymine, uracil), D-ribose or 2-deoxy-D-ribose and phosphoric acid.
High molecular weight, linear polymers, composed of nucleotides containing ribose and linked by phosphodiester bonds; RNA is central to the synthesis of proteins.
A carboxylic acid containing one or more amino groups.
Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.
An N-glycosyl compound that has both a nucleobase, normally adenine, guanine, xanthine, thymine, cytosine or uracil, and either a ribose or deoxyribose as functional parents.
Organic aromatic compounds having one or more hydroxy groups attached to a benzene or other arene ring.
A dibenzoazepine that is 5H-dibenzo[b,f]azepine carrying a carbamoyl substituent at the azepine nitrogen, used as an anticonvulsant.
A nitrosamine that is N-ethylethanamine substituted by a nitroso group at the N-atom.
A substance which is structurally similar to a metabolite but which competes with it or replaces it, and so prevents or reduces its normal utilization.
A substance that diminishes the rate of a chemical reaction.
A substance that increases the rate of a reaction without modifying the overall standard Gibbs energy change in the reaction.
Any drug that enhances the activity of the central nervous system.
Any of naturally occurring compounds and synthetic analogues, based on the cyclopenta[a]phenanthrene carbon skeleton, partially or completely hydrogenated; there are usually methyl groups at C-10 and C-13, and often an alkyl group at C-17. By extension, one or more bond scissions, ring expansions and/or ring contractions of the skeleton may have occurred. Natural steroids are derived biogenetically from triterpenoids.
SMILES: C12C(C3C(C(CC3)*)(C)CC1)CCC4C2(CCCC4)C
Parent monosaccharides are polyhydroxy aldehydes H[CH(OH)]nC(=O)H or polyhydroxy ketones H-[CHOH]n-C(=O)[CHOH]m-H with three or more carbon atoms. The generic term 'monosaccharide' (as opposed to oligosaccharide or polysaccharide) denotes a single unit, without glycosidic connection to other such units. It includes aldoses, dialdoses, aldoketoses, ketoses and diketoses, as well as deoxy sugars, provided that the parent compound has a (potential) carbonyl group.
A substance used in the prophylaxis or therapy of infectious diseases.
A substance used to treat or prevent parasitic infections.
Substance intended to kill parasitic worms (helminths).
A substance used in the treatment or control of nematode infestations.
Antidepressants are mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions.
A class of drugs producing both physiological and psychological effects through a variety of mechanisms involving the central nervous system.
A loosely defined grouping of drugs that have effects on psychological function.
A substance that reduces or suppresses inflammation.
A traditional grouping of drugs said to have a soothing or calming effect on mood, thought or behaviour.
Anxiolytic drugs are agents that alleviate anxiety, tension, and anxiety disorders, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions.
An anti-inflammatory drug that is not a steroid. In addition to anti-inflammatory actions, non-steroidal anti-inflammatory drugs have analgesic, antipyretic, and platelet-inhibitory actions. They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins.
Antipsychotic drugs are agents that control agitated psychotic behaviour, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect.
Antimanic drugs are agents used to treat bipolar disorders or mania associated with other affective disorders.
An agent capable of relieving pain without the loss of consciousness or without producing anaesthesia. In addition, analgesic is a role played by a compound which is exhibited by a capability to cause a reduction of pain symptoms.
A drug that has principally analgesic, antipyretic and anti-inflammatory actions. Non-narcotic analgesics do not bind to opioid receptors.
An EC 1.2.1.* (oxidoreductase acting on donor aldehyde/oxo group with NAD(+) or NADP(+) as acceptor) inhibitor that interferes with the action of aldehyde dehydrogenase (NAD(+)), EC 1.2.1.3.
CoA-independent aldehyde dehydrogenase inhibitor
CoA-independent aldehyde dehydrogenase inhibitors
EC 1.2.1.3 (aldehyde dehydrogenase (NAD(+))) inhibitor
EC 1.2.1.3 (aldehyde dehydrogenase (NAD(+))) inhibitors
EC 1.2.1.3 [aldehyde dehydrogenase (NAD(+))] inhibitors
NAD-dependent 4-hydroxynonenal dehydrogenase inhibitor
NAD-dependent 4-hydroxynonenal dehydrogenase inhibitors
NAD-dependent aldehyde dehydrogenase inhibitor
NAD-dependent aldehyde dehydrogenase inhibitors
NAD-linked aldehyde dehydrogenase inhibitor
NAD-linked aldehyde dehydrogenase inhibitors
aldehyde dehydrogenase (NAD(+)) (EC 1.2.1.3) inhibitor
aldehyde dehydrogenase (NAD(+)) (EC 1.2.1.3) inhibitors
aldehyde dehydrogenase (NAD(+)) inhibitor
aldehyde dehydrogenase (NAD(+)) inhibitors
m-methylbenzaldehyde dehydrogenase inhibitor
m-methylbenzaldehyde dehydrogenase inhibitors
propionaldehyde dehydrogenase inhibitors
EC 1.2.1.3 [aldehyde dehydrogenase (NAD(+))] inhibitor
A loosely defined group of drugs that tend to reduce the activity of the central nervous system.
A drug that prevents or reduces fever by lowering the body temperature from a raised state. An antipyretic will not affect the normal body temperature if one does not have fever. Antipyretics cause the hypothalamus to override an interleukin-induced increase in temperature. The body will then work to lower the temperature and the result is a reduction in fever.
A compound which inhibits or antagonises the biosynthesis or actions of androgens.
An agent that promotes the excretion of urine through its effects on kidney function.
A drug which lowers the blood glucose level.
An agent that binds to but does not activate beta-adrenergic receptors thereby blocking the actions of endogenous or exogenous beta-adrenergic agonists. beta-Adrenergic antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches and anxiety.
A compound or agent that combines with cyclooxygenases (EC 1.14.99.1) and thereby prevents its substrate-enzyme combination with arachidonic acid and the formation of icosanoids, prostaglandins, and thromboxanes.
(5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate,hydrogen-donor:oxygen oxidoreductase inhibitor
(5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate,hydrogen-donor:oxygen oxidoreductase inhibitors
EC 1.14.99.1 (cyclooxygenase) inhibitors
EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitors
cyclooxygenase (EC 1.14.99.1) inhibitors
prostaglandin endoperoxide synthetase inhibitor
prostaglandin endoperoxide synthetase inhibitors
EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor
A fluoroalkanoic acid that is perfluorinated octanoic acid.
Perhexiline (Pexsig) is a prophylactic antianginal agent used primarily in Australia and New Zealand. Perhexiline is thought to act by inhibiting mitochondrial carnitine palmitoyltransferase-1. (by Wikipedia)
A drug that affects the rate or intensity of cardiac contraction, blood vessel diameter or blood volume.
An agent that selectively binds to and activates alpha-adrenergic receptors.
A substance that inhibits or prevents the proliferation of neoplasms.
A drug used to cause dilation of the blood vessels.
A drug used to prevent seizures or reduce their severity.
An EC 1.17.3.* (oxidoreductase acting on CH or CH2 with oxygen as acceptor) inhibitor that interferes with the action of xanthine oxidase (EC 1.17.3.2).
EC 1.17.3.2 (xanthine oxidase) inhibitors
hypoxanthine-xanthine oxidase inhibitors
hypoxanthine:oxygen oxidoreductase inhibitor
hypoxanthine:oxygen oxidoreductase inhibitors
xanthine oxidase (EC 1.17.3.2) inhibitor
xanthine oxidase (EC 1.17.3.2) inhibitors
xanthine:oxygen oxidoreductase inhibitor
xanthine:oxygen oxidoreductase inhibitors
EC 1.17.3.2 (xanthine oxidase) inhibitor
Adrenergic uptake inhibitors are drugs that block the transport of adrenergic transmitters into axon terminals or into storage vesicles within terminals. The tricyclic antidepressants and amphetamines are among the therapeutically important drugs that may act via inhibition of adrenergic transport. Many of these drugs also block transport of serotonin.
An inhibitor of HIV protease, an enzyme required for production of proteins needed for viral assembly.
Any drug used in the treatment of acute or chronic vascular hypertension regardless of pharmacological mechanism.
A substance used to treat hyperlipidemia (an excess of lipids in the blood).
A xenobiotic (Greek, xenos "foreign"; bios "life") is a compound that is foreign to a living organism. Principal xenobiotics include: drugs, carcinogens and various compounds that have been introduced into the environment by artificial means.
An agent that suppresses immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-cells or by inhibiting the activation of helper cells. In addition, an immunosuppressive agent is a role played by a compound which is exhibited by a capability to diminish the extent and/or voracity of an immune response.
A central nervous system depressant used to induce drowsiness or sleep or to reduce psychological excitement or anxiety.
An antimicrobial agent that destroys fungi by suppressing their ability to grow or reproduce.
Any member of the group of lipids containing a common glycerol backbone to which at least one fatty acid-derived group is attached.
A substance that suppresses Mycobacterium leprae, ameliorates the clinical manifestations of leprosy, and/or reduces the incidence and severity of leprous reactions.
Any antimicrobial drug which is used to treat or prevent protozoal infections.
A substance used to lower plasma cholesterol levels.
A gout suppressant that acts directly on the renal tubule to increase the excretion of uric acid, thus reducing its concentrations in plasma.
A drug used to treat rheumatoid arthritis.
A drug that increases uric acid excretion by the kidney (uricosuric drug), decreases uric acid production (antihyperuricemic), or alleviates the pain and inflammation of acute attacks of gout.
A drug used for its effect on the kidneys' regulation of body fluid composition and volume.
A compound or agent that combines with lipoxygenase and thereby prevents its substrate-enzyme combination with arachidonic acid and the formation of the icosanoid products hydroxyicosatetraenoic acid and various leukotrienes.
A substance used for its pharmacological action on any aspect of neurotransmitter systems. Neurotransmitter agents include agonists, antagonists, degradation inhibitors, uptake inhibitors, depleters, precursors, and modulators of receptor function.
A drug used to treat or prevent microbial infections.
A substance used in the prophylaxis or therapy of virus diseases.
A drug used to treat or prevent bacterial infections.
An amino acid chain that is produced de novo by ribosome-mediated translation of a genetically-encoded mRNA.
A 1,3-thiazine that is 1,3-thiazinan-4-one S,S-dioxide in which a hydrogen at position 2 is substituted by a 4-chlorophenyl group and the hydrogen attached to the nitrogen is substituted by methyl. A non-benzodiazepine muscle relaxant, it was used in the management of anxiety and in the treatment of muscle spasms until being discontinued worldwide by its manufacturer in 1996, due to rare but serious cutaneous reactions.
2-(4-chlorophenyl)-3-methyl-1,3-thiazinan-4-one 1,1-dioxide
2-(p-chlorophenyl)tetrahydro-3-methyl-4H-1,3-thiazin-4-one 1,1-dioxide
Any glycerophospholipid having the polar alcohol inositol esterified to the phosphate group at the sn-3 position of the glycerol backbone.
A drug used to treat or prevent infections caused by protozoal organisms belonging to the suborder Trypanosomatida.
Any molecular entity consisting of more than one atom.
An organochlorine compound comprising acetic acid carrying two chloro substituents at the 2-position. It occurs in nature in seaweed, Asparagopsis taxiformis.
A compound which stimulates anabolism and inhibits catabolism. Anabolic agents stimulate the development of muscle mass, strength, and power.
A substituted phenothiazine in which the ring nitrogen at position 10 is attached to C-3 of an N,N-dimethylpropanamine moiety.
A member of the class of 1,3-benzoxazoles that is 1,3-benzoxazol-2-ol in which the hydrogen atom at position 5 is substituted by chlorine. A centrally acting muscle relaxant with sedative properties, it is used for the symptomatic treatment of painful muscle spasm.
An N,N-disubstituted benzenesulfonamide bearing an unsubstituted amino group at the 4-position, used for the treatment of HIV infection. A second-generation HIV protease inhibitor, darunavir was designed to form robust interactions with the protease enzyme from many strains of HIV, including those from treatment-experienced patients with multiple resistance mutations to other protease inhibitors.
(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl [(2S,3R)-4-{[(4-aminophenyl)sulfonyl](2-methylpropyl)amino}-3-hydroxy-1-phenylbutan-2-yl]carbamate
(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl N-((1S,2R)-1-benzyl-2-hydroxy-3-(N(1)-isobutylsulfanilamido)propyl)carbamate
(3R,3aS,6aR)-tetrahydro-2H-furo[2,3-b]furan-3-yl (2S,3R)-4-(4-amino-N-isobutylphenylsulfonamido)-3-hydroxy-1-phenylbutan-2-ylcarbamate
(3R,3aS,6aR)-tetrahydro-2H-furo[2,3-b]furan-3-yl (2S,3R)-4-(4-amino-N-neopentylphenylsulfonamido)-3-hydroxy-1-phenylbutan-2-ylcarbamate
[(S)-3-[(4-Amino-benzenesulfonyl)-isobutyl-amino]-2-hydroxy-1-((R)-phenylmethyl)-propyl]-carbamic acid (3R,3aS,6aR)-(hexahydro-furo[2,3-b]furan-3-yl) ester
{(1S,2R)-3-[(4-Amino-benzenesulfonyl)-isobutyl-amino]-1-benzyl-2-hydroxy-propyl}-carbamic acid (3R,3aS,6aR)-(hexahydro-furo[2,3-b]furan-3-yl) ester
A nucleotide is a nucleoside phosphate resulting from the condensation of the 3 or 5 hydroxy group of a nucleoside with phosphoric acid.
A nucleotide consists of a nitrogen-containing base, a five-carbon sugar, and one or more phosphate groups. Nucleotides can carry chemical energy (e.g. ATP), form coenzymes (e.g. CoA), be used as specific signaling molecules (e.g. cAMP) in the cell. Nucleotides are the subunits of the nucleic acids.
Any EC 3.1.3.* (phosphoric monoester hydrolase) inhibitor that interferes with the action of phosphoprotein phosphatase (EC 3.1.3.16).
3-hydroxy 3-methylglutaryl coenzymeA reductase phosphatase inhibitor
3-hydroxy 3-methylglutaryl coenzymeA reductase phosphatase inhibitors
Aspergillus awamori acid protein phosphatase inhibitor
Aspergillus awamori acid protein phosphatase inhibitors
EC 3.1.3.16 (protein serine/threonine phosphatase) inhibitors
HMG-CoA reductase phosphatase inhibitors
branched-chain alpha-keto acid dehydrogenase phosphatase inhibitor
branched-chain alpha-keto acid dehydrogenase phosphatase inhibitors
phosphoprotein phosphatase (EC 3.1.3.16) inhibitor
phosphoprotein phosphatase (EC 3.1.3.16) inhibitors
phosphoprotein phosphohydrolase inhibitor
phosphoprotein phosphohydrolase inhibitors
phosphopyruvate dehydrogenase phosphatase inhibitor
phosphopyruvate dehydrogenase phosphatase inhibitors
polycation modulated (PCM-) phosphatase inhibitor
polycation modulated (PCM-) phosphatase inhibitors
protein serine/threonine phosphatase (EC 3.1.3.16) inhibitors
protein serine/threonine phosphatase inhibitor
protein serine/threonine phosphatase inhibitors
serine/threonine specific protein phosphatase inhibitor
serine/threonine specific protein phosphatase inhibitors
EC 3.1.3.16 (phosphoprotein phosphatase) inhibitor
The 6-O-methyl ether of erythromycin A, clarithromycin is a macrolide antibiotic used in the treatment of respiratory-tract, skin and soft-tissue infections. It is also used to eradicate Helicobacter pylori in the treatment of peptic ulcer disease. It prevents bacteria from growing by interfering with their protein synthesis.
ethyl 2-(4-chlorophenoxy)-2-methylpropanoate
An acid is a molecular entity capable of donating a hydron (Bronsted acid) or capable of forming a covalent bond with an electron pair (Lewis acid).
A phosphosphingolipid that consists of sphingosine having a phospho group attached at position 1
Sphingolipid mediators, such as sphingosine 1-phosphate (S1P), ceramide, and sphingosine are derived by the enzymatic breakdown of sphingomyelin, an abundant membrane phospholipid. S1P is an evolutionarily conserved bioactive lipid mediator with potent effects on multiple organ systems.
An acyl-CoA that results from the formal condensation of the thiol group of coenzyme A with the carboxy group of any fatty acid.
A benzodiazepine that is 5H-dibenzo[b,e][1,4]diazepine substituted by a chloro group at position 8 and a 4-methylpiperazin-1-yl group at position 11. It is a second generation antipsychotic used in the treatment of psychiatric disorders like schizophrenia.
A compound which inhibits or antagonizes the biosynthesis or actions of proteases (endopeptidases).
An EC 2.7.* (P-containing group transferase) inhibitor that interferes with the action of protein kinases.
An EC 2.7.11.* (protein-serine/threonine kinase) inhibitor that interferes with the action of protein kinase C (EC 2.7.11.13).
ATP:protein phosphotransferase (diacylglycerol-dependent) inhibitor
ATP:protein phosphotransferase (diacylglycerol-dependent) inhibitors
EC 2.7.11.13 (protein kinase C) inhibitors
calcium-dependent protein kinase C inhibitor
calcium-dependent protein kinase C inhibitors
calcium-independent protein kinase C inhibitor
calcium-independent protein kinase C inhibitors
calcium/phospholipid dependent protein kinase inhibitor
calcium/phospholipid dependent protein kinase inhibitors
protein kinase C (EC 2.7.11.13) inhibitor
protein kinase C (EC 2.7.11.13) inhibitors
EC 2.7.11.13 (protein kinase C) inhibitor
An EC 3.1.1.* (carboxylic ester hydrolase) inhibitor that interferes with the action of cholinesterase (EC 3.1.1.8).
choline esterase II (unspecific) inhibitor
choline esterase II (unspecific) inhibitors
Any glycerolipid having a phosphate group ester-linked to a terminal carbon of the glycerol backbone.
A hormone that specifically regulates growth.
An agent that selectively binds to and activates adrenergic receptors.
An agent that binds to but does not activate adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists.
An agent that binds to but does not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous alpha-adrenergic agonists. alpha-Adrenergic antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma.
A heavily substituted carbohydrazide that is an antiretroviral drug of the protease inhibitor (PI) class used to treat infection of human immunodeficiency virus (HIV).
dimethyl (3S,8S,9S,12S)-9-benzyl-3,12-di-tert-butyl-8-hydroxy-4,11-dioxo-6-[4-(2-pyridyl)benzyl]-2,5,6,10,13-pentaazatetradecanedioate
Histamine antagonists are the drugs that bind to but do not activate histamine receptors, thereby blocking the actions of histamine or histamine agonists.
Drugs used for their actions on histaminergic systems.
Any agent that acts on an adrenergic receptor or affects the life cycle of an adrenergic transmitter.
A drug used in the treatment of malaria. Antimalarials are usually classified on the basis of their action against Plasmodia at different stages in their life cycle in the human.
A drug used for the treatment or prevention of cardiac arrhythmias. Anti-arrhythmia drugs may affect the polarisation-repolarisation phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibres.
A drug that has a strengthening effect on the heart or that can increase cardiac output.
A ligand with two or more separate binding sites that can bind to a single metallic central atom, forming a chelate.
A hydrochloride that is the monohydrochloride salt of methapyrilene.
N,N-dimethyl-N'-pyridin-2-yl-N'-[(thiophen-2-yl)methyl]ethane-1,2-diamine hydrochloride
A member of the class of phhenylureas that is urea in which one of the nitrogens is substituted by a p-chlorophenyl group while the other is substituted by two methyl groups.
One of a class of drugs that acts by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools.
A diester that results from the condensation of the 1-carboxy groups of two molecules of propane-1,2,3-tricarboxylic acid with hydroxy groups at positions 14 and 15 of (2S,3S,5R,10R,12S,14S,15R,16R)-2-amino-12,16-dimethylicosane-3,5,10,14,15-pentol.
(2R,2'R)-2,2'-{[(5R,6R,7S,9S,11R,16R,18S,19S)-19-amino-11,16,18-trihydroxy-5,9-dimethylicosane-6,7-diyl]bis[oxy(2-oxoethane-2,1-diyl)]}dibutanedioic acid
Any drug used for its actions on cholinergic systems. Included here are agonists and antagonists, drugs that affect the life cycle of acetylcholine, and drugs that affect the survival of cholinergic neurons.
An EC 3.1.1.* (carboxylic ester hydrolase) inhibitor that interferes with the action of enzyme acetylcholinesterase (EC 3.1.1.7), which helps breaking down of acetylcholine into choline and acetic acid.
EC 3.1.1.7 (acetylcholinesterase) inhibitor role
A role played by the entity that inhibits the electron-transport chain
A role played by the entity that inhibits the respiratory-chain.
A respiratory-chain inhibitor that interferes with the action of the the enzyme NADH:ubiquinone reductase (H(+)-translocating), EC 1.6.5.3.
EC 1.6.5.3 (NADH:ubiquinone reductase (H(+)-translocating)) inhibitor
EC 1.6.5.3 (NADH:ubiquinone reductase (H(+)-translocating)) inhibitors
EC 1.6.5.3 [NADH:ubiquinone reductase (H(+)-translocating)] inhibitors
NADH dehydrogenase (ubiquinone) inhibitor
NADH dehydrogenase (ubiquinone) inhibitors
NADH-coenzyme Q oxidoreductase inhibitors
NADH-ubiquinone oxidoreductase inhibitor
NADH-ubiquinone oxidoreductase inhibitors
NADH2 dehydrogenase (ubiquinone) inhibitor
NADH:ubiquinone oxidoreductase complex inhibitor
NADH:ubiquinone oxidoreductase inhibitor
NADH:ubiquinone oxidoreductase inhibitors
NADH:ubiquinone reductase (H(+)-translocating) inhibitor
NADH:ubiquinone reductase (H(+)-translocating) inhibitors
NADH:ubiquinone reductase (H+-translocating) inhibitor
complex I (NADH:Q1 oxidoreductase) inhibitors
complex I (electron transport chain) inhibitors
complex I (mitochondrial electron transport) inhibitors
dihydronicotinamide adenine dinucleotide-coenzyme Q reductase inhibitor
mitochondrial electron transport complex 1 inhibitor
mitochondrial electron transport complex I inhibitor
mitochondrial electron transport complex I inhibitors
reduced nicotinamide adenine dinucleotide-coenzyme Q reductase inhibitor
reduced nicotinamide adenine dinucleotide-coenzyme Q reductase inhibitors
EC 1.6.5.3 [NADH:ubiquinone reductase (H(+)-translocating)] inhibitor
Any agent that affects the transport of molecular entities across a biological membrane.
An agent that inhibits sodium influx through cell membranes.
Any protein kinase inhibitor that interferes with the action of tyrosine kinase.
Agents that increase calcium influx into calcium channels of excitable tissues.
A membrane transport modulator that is able to regulate intracellular calcium levels.
A class of lipoproteins of small size (4-13 nm) and dense (greater than 1.063 g/ml) particles. They are synthesized in the liver without a lipid core, accumulate cholesterol esters from peripheral tissues and transport them to the liver for re-utilization or elimination from the body (the reverse cholesterol transport).
A class of lipoproteins of large size (30-80 nm), very low density (0.93-1.006 g/ml) particles with a core composed mainly of triglycerides and a surface monolayer of phospholipids and cholesterol into which are imbedded the apolipoproteins B, E, and C. VLDL facilitate the transport of endogenously made triglycerides to extrahepatic tissues.
The active insecticidal constituents of Chrysanthemum cinerariifolium flowers.
A dihydroxy monocarboxylic acid that is a member of the drug class known as statins, used primarily for lowering blood cholesterol and for preventing cardiovascular diseases.
(3R,5R)-7-[3-(anilinocarbonyl)-5-(4-fluorophenyl)-4-phenyl-2-(propan-2-yl)-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid
(R-(R*,R*))-2-(4-Fluorophenyl)-beta,delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4-((phenylamino)carbonyl)-1H-pyrrole-1-heptanoic acid
7-[2-(4-FLUORO-PHENYL)-5-ISOPROPYL-3-PHENYL-4-PHENYLCARBAMOYL-PYRROL-1-YL]-3,5-DIHYDROXY-HEPTANOIC ACID
An organofluorine compound comprising salicylic acid having a 2,4-difluorophenyl group at the 5-position.
2',4'-difluoro-4-hydroxy-[1,1'-biphenyl]-3-carboxylic acid
2',4'-difluoro-4-hydroxy-3-biphenylcarboxylic acid
2-(hydroxy)-5-(2,4-difluorophenyl)benzoic acid
A branched-chain saturated fatty acid that comprises of a propyl substituent on a pentanoic acid stem.
A bicyclic structure comprising a pyrazole ring fused to a hydroxy-substituted pyrimidine ring.
A cyclic nonribosomal peptide of eleven amino acids; an immunosuppressant drug widely used in post-allogeneic organ transplant to reduce the activity of the patient's immune system, and therefore the risk of organ rejection. Also causes reversible inhibition of immunocompetent lymphocytes in the G0- and G1-phase of the cell cycle.
Tamoxifen, sold under the brand name Nolvadex among others, is a medication that is used to prevent breast cancer in women and treat breast cancer in women and men. (by Wikipedia)
A 2,6-diaminopurine that is (1S)-cyclopent-2-en-1-ylmethanol in which the pro-R hydrogen at the 4-position is substituted by a 2-amino-6-(cyclopropylamino)-9H-purin-9-yl group. A nucleoside analogue reverse transcriptase inhibitor (NRTI) with antiretroviral activity against HIV, it is used (particularly as the sulfate) with other antiretrovirals in combination therapy of HIV infection.
An erythromycin that consists of erythronolide A having 2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl and 3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl residues attahced at positions 4 and 6 respectively.
A monocarboxylic acid amide that is 1H-imidazole-4-carboxamide which is substituted at position 5 by a 3,3-dimethyltriaz-1-en-1-yl group. It is used for the treatment of metastatic malignant melanoma, and in combination with other drugs for the treatment of Hodgkin's disease and soft-tissue sarcoma.
Imidazole-4-carboxamide, 5-(3,3-dimethyl-1-triazeno)-
The hydrazone resulting from the formal condensation of 5-(4-nitrophenyl)furfural with 1-aminohydantoin.
N-(4-{[(2,4-diaminopteridin-6-yl)methyl](methyl)amino}benzoyl)-L-glutamic acid
4-amino-N(10)-methylpteroylglutamic acid
N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamic acid
A mucopolysaccharide consisting of repeating beta-(1->4)-linked L-iduronyl-(beta1->3)-N-acetyl-D-galactosamine units.
A member of the class of ureas that is urea in which one of the hydrogens is replaced by a hydroxy group. An antineoplastic used in the treatment of chronic myeloid leukaemia as well as for sickle-cell disease.
An aromatic ether having phenyl and 2-methylsulfonamido-5-nitrophenyl as the two aryl groups.
An L-valine derivative that is an antiretroviral drug from the protease inhibitor class used to treat HIV infection and AIDS, it is often used as a fixed-dose combination with another protease inhibitor, lopinavir. Also used in combination with dasabuvir sodium hydrate, ombitasvir and paritaprevir (under the trade name Viekira Pak) for treatment of chronic hepatitis C virus genotype 1 infection as well as cirrhosis of the liver.
A benzamide obtained by formal condensation of the carboxy group of 4-[(4-methylpiperazin-1-yl)methyl]benzoic acid with the primary aromatic amino group of 4-methyl-N(3)-[4-(pyridin-3-yl)pyrimidin-2-yl]benzene-1,3-diamine. Used (as its mesylate salt) for treatment of chronic myelogenous leukemia and gastrointestinal stromal tumours.
A member of the class of benzimidazoles carrying a 1,3-thiazol-4-yl substituent at position 2. A mainly post-harvest fungicide used to control a wide range of diseases including Aspergillus, Botrytis, Cladosporium and Fusarium.
A member of the class of acridines that is 1,2,3,4-tetrahydroacridine substituted by an amino group at position 9. It is used in the treatment of Alzheimer's disease.
A member of the class of triazoles that is propan-2-ol substituted at position 1 and 3 by 1H-1,2,4-triazol-1-yl groups and at position 2 by a 2,4-difluorophenyl group. It is an antifungal drug used for the treatment of mucosal candidiasis and for systemic infections including systemic candidiasis, coccidioidomycosis, and cryptococcosis.
2,4-difluoro-alpha,alpha-bis(1H-1,2,4-triazol-1-ylmethyl)benzyl alcohol
A member of the class of phenols that is 4-aminophenol in which one of the hydrogens attached to the amino group has been replaced by an acetyl group.
An organic disulfide that results from the formal oxidative dimerisation of N,N-diethyldithiocarbamic acid. A multi-enzyme inhibitor that is used in alcohol aversion therapy and also exhibits anticancer properties.
A liquid that can dissolve other substances (solutes) without any change in their chemical composition.
A monocarboxylic acid consisting of phenylacetic acid having a (2,6-dichlorophenyl)amino group at the 2-position.
2-[(2,6-dichlorophenyl)amino]benzeneacetic acid
{2-[(2,6-dichlorophenyl)amino]phenyl}acetic acid
2-((2,6-dichlorophenyl)amino)benzeneacetic acid
[2-(2,6-dichloroanilino)phenyl]acetic acid
A semisynthetic cyclic hexapeptide echinocandin antibiotic which exerts its effect by inhibiting the synthesis of 1,3-beta-D-glucan, an integral component of the fungal cell wall.
(4R,5S)-5-((2-aminoethyl)amino)-N(2)-(10,12-dimethyltetradecanoyl)-4-hydroxy-L-ornithyl-L-threonyl-trans-4-hydroxy-L-prolyl-(S)-4-hydroxy-4-(p-hydroxyphenyl)-L-threonyl-threo-3-hydroxy-L-ornithyl-trans-3-hydroxy-L-proline cyclic (6-1)-peptide
1-[(4R,5S)-5-[(2-aminoethyl)amino]-N(2)-(10,12-dimethyl-1-oxotetradecyl)-4-hydroxy-L-ornithine]-5-[(3R)-3-hydroxy-L-ornithine]-pneumocandin B0
Imipramine is a tricyclic antidepressant that continues to be widely used in the therapy of depression. Imipramine can cause mild and transient serum enzyme elevations and is rare cause of clinically apparent acute cholestatic liver injury.
A racemate consisting of equimolar amounts of (2R,4S)- and (2S,4R)-ketoconazole.
A dibenzoazepine that is 10,11-dihydro-5H-dibenzo[b,f]azepine which is substituted by chlorine at position 3 and in which the hydrogen attached to the nitrogen is replaced by a 3-(dimethylamino)propyl group. One of the more sedating tricyclic antidepressants, it is used as the hydrochloride salt for the treatment of depression as well as obsessive-compulsive disorder and phobias.
A chemical compound that can be excited by light of a specific wavelength and subsequently transfer energy to a chosen reactant. This is commonly molecular oxygen within a cancer tissue, which is converted to (highly rective) singlet state oxygen. This rapidly reacts with any nearby biomolecules, ultimately killing the cancer cells.
A compound, usually an anti-bacterial agent or a toxin, which inhibits the synthesis of a protein.
Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or serotonergic agonists.
An EC 2.1.1.* (methyltransferase) inhibitor that interferes with the action of catechol O-methyltransferase (EC 2.1.1.6).
EC 2.1.1.6 (catechol O-methyltransferase) inhibitors
S-adenosyl-L-methionine:catechol O-methyltransferase inhibitor
S-adenosyl-L-methionine:catechol O-methyltransferase inhibitors
catechol O-methyltransferase (EC 2.1.1.6) inhibitor
catechol O-methyltransferase (EC 2.1.1.6) inhibitors
catecholamine O-methyltransferase inhibitor
catecholamine O-methyltransferase inhibitors
EC 2.1.1.6 (catechol O-methyltransferase) inhibitor
A drug used in the treatment of Parkinson's disease.
An agent and endogenous substances that antagonize or inhibit the development of new blood vessels.
Any drug that acts on an alpha-adrenergic receptor.
Any of the drugs that act on beta-adrenergic receptors.
An EC 1.1.1.* (oxidoreductase acting on donor CH-OH group, NAD(+) or NADP(+) acceptor) inhibitor that interferes with the action of aldehyde reductase (EC 1.1.1.21).
EC 1.1.1.21 (aldehyde reductase) inhibitors
aldehyde reductase (EC 1.1.1.21) inhibitor
aldehyde reductase (EC 1.1.1.21) inhibitors
alditol:NAD(P)(+) 1-oxidoreductase inhibitor
alditol:NAD(P)(+) 1-oxidoreductase inhibitors
alditol:NADP(+) 1-oxidoreductase inhibitor
alditol:NADP(+) 1-oxidoreductase inhibitors
polyol dehydrogenase (NADP(+)) inhibitor
polyol dehydrogenase (NADP(+)) inhibitors
EC 1.1.1.21 (aldehyde reductase) inhibitor
A drug used for its effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons.
A drug that binds to but does not activate dopamine receptors, thereby blocking the actions of dopamine or exogenous agonists.
A role played by a substance that can react readily with, and thereby eliminate, radicals.
A drug that affects the function of fibrin in blood coagulation.
A carbamate ester obtained by the formal condensation of the hydroxy group of 17beta-estradiol with the carboxy group of bis(2-chloroethyl)carbamic acid.
(17beta)-17-hydroxyestra-1(10),2,4-trien-3-yl bis(2-chloroethyl)carbamate
17beta-Estradiol 3-(bis(2-chloroethyl)carbamate)
Estradiol 3-(N,N-bis(2-chloroethyl)carbamate)
Substance which binds to cell receptors normally responding to naturally occurring substances and which produces a response of its own.
Substance that attaches to and blocks cell receptors that normally bind naturally occurring substances.
An ethylenediamine derivative that is ethane-1,2-diamine in which one hydrogen attached to each of the nitrogens is sutstituted by a 1-hydroxybutan-2-yl group (S,S-configuration). It is a bacteriostatic antimycobacterial drug, effective against Mycobacterium tuberculosis and some other mycobacteria. It is used (as the dihydrochloride salt) in combination with other antituberculous drugs in the treatment of pulmonary and extrapulmonary tuberculosis; resistant strains of M. tuberculosis are readily produced if ethambutol is used alone.
A thiocarboxamide that is pyridine-4-carbothioamide substituted by an ethyl group at position 2. A prodrug that undergoes metabolic activation by conversion to the corresponding S-oxide.
Any drug that binds to but does not activate cholinergic receptors, thereby blocking the actions of acetylcholine or cholinergic agonists.
A drug that binds to but does not activate muscarinic cholinergic receptors, thereby blocking the actions of endogenous acetylcholine or exogenous agonists.
muscarinic acetylcholine receptor antagonist
Metabolites of bile acids, four-ringed steroid acids formed along the cholesterol degradation pathway.
Any of several wide-spectrum macrolide antibiotics obtained from actinomycete Saccharopolyspora erythraea (formerly known as Streptomyces erythraeus).
A member of the class of triazoles, deferasirox is 1,2,4-triazole substituted by a 4-carboxyphenyl group at position 1 and by 2-hydroxyphenyl groups at positions 3 and 5. An orally active iron chelator, it is used to manage chronic iron overload in patients receiving long-term blood transfusions.
4-[3,5-bis(2-hydroxyphenyl)-1H-1,2,4-triazol-1-yl]benzoic acid
A chemical substance which inhibits the function of the endocrine glands, the biosynthesis of their secreted hormones, or the action of hormones upon their specific sites.
A purine 2',3'-dideoxyribonucleoside that is inosine in which the hydroxy groups at both the 2' and the 3' positions on the sugar moiety have been replaced by hydrogen. An antiviral drug, it is used as a medication to treat HIV/AIDS.
A monocarboxylic acid that is acetic acid in which one of the methyl hydrogens is substituted by a 1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-yl moiety. A preferential inhibitor of cyclo-oxygenase 2 and non-steroidal anti-inflammatory, it is used for the treatment of rheumatoid arthritis and osteoarthritis, and for the alleviation of postoperative pain. Administered as the racemate, only the (S)-enantiomer is active.
(1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-yl)acetic acid
(+-)-1,8-diethyl-1,3,4,9-tetrahydropyrano(3,4-b)indole-1-acetic acid
(1,8-Diethyl-1,3,4,9-tetrahydro-pyrano[3,4-b]indol-1-yl)-acetic acid
1,3,4,9-tetrahydro-1,8-diethylpyrano(3,4-b)indole-1-acetic acid
1,8-diethyl-1,3,4,9-tetrahydropyrano(3,4-b)indole-1-acetic acid
1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-ylacetic acid
Any human metabolite produced by metabolism of drugs in humans.
A drug designed to prevent leukotriene synthesis or activity by blocking binding at the receptor level.
One of various classes of drugs with different action mechanisms used to treat or ameliorate peptic ulcer or irritation of the gastrointestinal tract.
A chemical substance that prevents or reduces the probability of conception.
A chemical substance or agent with contraceptive activity in females.
A 17-oxo steroid that is androsta-1,4-diene-3,17-dione in which the hydrogens at position 6 are replaced by a double bond to a methylene group. A selective inhibitor of the aromatase (oestrogen synthase) system, it is used in the treatment of advanced breast cancer.
A member of the class of quinazolines that is quinazoline which is substituted by a (3-chloro-4-fluorophenyl)nitrilo group, 3-(morpholin-4-yl)propoxy group and a methoxy group at positions 4,6 and 7, respectively. An EGFR kinase inhibitor used for the treatment of non-small cell lung cancer.
The bis(carbamate ester) of 2-phenylpropane-1,3-diol. An anticonvulsant, it is used in the treatment of epilepsy.
Carbamic acid 3-carbamoyloxy-2-phenyl-propyl ester
carbamic acid 2-phenyltrimethylene ester
A chlorobenzophenone that is (4-chlorophenyl)(phenyl)methanone substituted by a [2-methyl-1-oxo-1-(propan-2-yloxy)propan-2-yl]oxy group at position 1 on the phenyl ring.
propan-2-yl 2-[4-(4-chlorobenzoyl)phenoxy]-2-methylpropanoate
A monocarboxylic acid that is propanoic acid in which one of the hydrogens at position 2 is substituted by a 3-phenoxyphenyl group. A non-steroidal anti-inflammatory drug, the dihydrate form of the calcium salt is used for the management of mild to moderate pain and for the relief of pain and inflammation associated with disorders such as arthritis. It is pharmacologically similar to aspirin, but causes less gastrointestinal bleeding.
alpha-methyl-3-phenoxybenzeneacetic acid
Any hormone that is responsible for controlling sexual characteristics and reproductive function.
A sex hormone that stimulates or controls the development and maintenance of masculine characteristics in vertebrates by binding to androgen receptors.
A hormone that stimulates or controls the development and maintenance of female sex characteristics in mammals by binding to oestrogen receptors. The oestrogens are named for their importance in the oestrous cycle. The oestrogens that occur naturally in the body, notably estrone, estradiol, estriol, and estetrol are steroids. Other compounds with oestrogenic activity are produced by plants (phytoestrogens) and fungi (mycoestrogens); synthetic compounds with oestrogenic activity are known as xenoestrogens.
A retinoid that consists of 3,7-dimethylnona-2,4,6,8-tetraenoic acid having a 4-methoxy-2,3,6-trimethylphenyl group attached at position 9.
9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenoic acid
A drug that softens, separates, and causes desquamation of the cornified epithelium or horny layer of skin. Keratolytic drugs are used to expose mycelia of infecting fungi or to treat corns, warts, and certain other skin diseases.
A drug used to treat or prevent skin disorders or for the routine care of skin.
An enzyme inhibitor that interferes with the activity of cytochrome P450 involved in catalysis of organic substances.
Any pathway inhibitor that inhibits the synthesis of fatty acids.
Drug that acts on blood and blood-forming organs and those that affect the hemostatic system.
A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.
Synthetic or natural substance which is given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent.
A topoisomerase inhibitor that inhibits the bacterial enzymes of the DNA topoisomerases, Type I class (EC 5.99.1.2) that catalyze ATP-independent breakage of one of the two strands of DNA, passage of the unbroken strand through the break, and rejoining of the broken strand. These bacterial enzymes reduce the topological stress in the DNA structure by relaxing negatively, but not positively, supercoiled DNA.
EC 5.99.1.2 (DNA topoisomerase) inhibitors
EC 5.99.1.2 (topoisomerase I) inhibitors
topoisomerase I (EC 5.99.1.2) inhibitors
EC 5.99.1.2 (DNA topoisomerase) inhibitor
A drug or agent which antagonizes or impairs any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system.
An EC 3.1.1.* (carboxylic ester hydrolase) inhibitor that interferes with the action of phospholipase A2 (EC 3.1.1.4).
An EC 2.5.1.* (non-methyl-alkyl or aryl transferase) inhibitor that interferes with the action of dihydropteroate synthase (EC 2.5.1.15), an enzyme that catalyzes the formation of dihydropteroate from p-aminobenzoic acid and dihydropteridine-hydroxymethyl-pyrophosphate.
(2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl-diphosphate:4-aminobenzoate 2-amino-4-hydroxydihydropteridine-6-methenyltransferase inhibitor
(2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl-diphosphate:4-aminobenzoate 2-amino-4-hydroxydihydropteridine-6-methenyltransferase inhibitors
2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine-diphosphate:4-aminobenzoate 2-amino-4-hydroxydihydropteridine-6-methenyltransferase inhibitor
2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine-diphosphate:4-aminobenzoate 2-amino-4-hydroxydihydropteridine-6-methenyltransferase inhibitors
7,8-dihydropteroate synthetase inhibitor
7,8-dihydropteroate synthetase inhibitors
7,8-dihydropteroic acid synthetase inhibitor
7,8-dihydropteroic acid synthetase inhibitors
EC 2.5.1.15 (dihydropteroate synthase) inhibitors
dihydropteroate diphosphorylase inhibitor
dihydropteroate diphosphorylase inhibitors
dihydropteroate pyrophosphorylase inhibitor
dihydropteroate pyrophosphorylase inhibitors
dihydropteroate synthase (EC 2.5.1.15) inhibitor
dihydropteroate synthase (EC 2.5.1.15) inhibitors
EC 2.5.1.15 (dihydropteroate synthase) inhibitor
Drug used to cause constriction of the blood vessels.
An EC 3.2.1.* (glycosidase) inhibitor that interferes with the action of alpha-amylase (EC 3.2.1.1).
1,4-alpha-D-glucan glucanohydrolase inhibitor
1,4-alpha-D-glucan glucanohydrolase inhibitors
4-alpha-D-glucan glucanohydrolase inhibitor
4-alpha-D-glucan glucanohydrolase inhibitors
A cyclooxygenase inhibitor that interferes with the action of cyclooxygenase 2.
prostaglandin-endoperoxide synthase 2 inhibitor
prostaglandin-endoperoxide synthase 2 inhibitors
A cyclooxygenase inhibitor that interferes with the action of cyclooxygenase 1.
prostaglandin-endoperoxide synthase 1 inhibitor
prostaglandin-endoperoxide synthase 1 inhibitors
An agent that inhibits bone resorption and/or favor bone mineralization and bone regeneration. Used to heal bone fractures and to treat bone diseases such as osteopenia and osteoporosis.
A drug used to treat hyperthyroidism by reducing the excessive production of thyroid hormones.
A member of the class of imidazoles that it imidazole-2-thione in which a methyl group replaces the hydrogen which is attached to a nitrogen.
An EC 1.5.1.* (oxidoreductase acting on donor CH-NH group, NAD(+) or NADP(+) as acceptor) inhibitor that interferes with the action of dihydrofolate reductase (EC 1.5.1.3).
EC 1.5.1.3 (dihydrofolate reductase) inhibitors
NADPH-dihydrofolate reductase inhibitors
dihydrofolate reductase (EC 1.5.1.3) inhibitor
dihydrofolate reductase (EC 1.5.1.3) inhibitors
tetrahydrofolate dehydrogenase inhibitor
tetrahydrofolate dehydrogenase inhibitors
EC 1.5.1.3 (dihydrofolate reductase) inhibitor
A substance used either in the prevention or facilitation of pregnancy.
A chemical substance that interrupts pregnancy after implantation.
A tetracycline analogue having a dimethylamino group at position 7 and lacking the methyl and hydroxy groups at position 5.
A substance that possess antiestrogenic actions but can also produce estrogenic effects as well. It acts as complete or partial agonist or as antagonist. It can be either steroidal or nonsteroidal in structure.
6-chloro-3,20-dioxo-1beta,2beta-dihydro-3'H-cyclopropa[1,2]pregna-4,6-dien-17-yl acetate
A compound that interacts with progesterone receptors in target tissues to bring about effects similar to those of progesterone.
A topoisomerase inhibitor that inhibits DNA topoisomerase (ATP-hydrolysing), EC 5.99.1.3 (also known as topoisomerase II and as DNA gyrase), which catalyses ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands.
DNA topoisomerase (ATP-hydrolysing) (EC 5.99.1.3) inhibitor
DNA topoisomerase (ATP-hydrolysing) (EC 5.99.1.3) inhibitors
DNA topoisomerase (ATP-hydrolysing) inhibitor
DNA topoisomerase (ATP-hydrolysing) inhibitors
EC 5.99.1.3 (DNA topoisomerase (ATP-hydrolysing)) inhibitor
EC 5.99.1.3 (DNA topoisomerase (ATP-hydrolysing)) inhibitors
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitors
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor
A drug which acts to reduce estrogenic activity in the body, either by reducing the amount of estrogen or by reducing the activity of whatever estrogen is present.
An EC 1.14.14.* (oxidoreductase acting on paired donors, incorporating of 1 atom of oxygen, with reduced flavin or flavoprotein as one donor) inhibitor which interferes with the action of aromatase (EC 1.14.14.14) and so reduces production of estrogenic steroid hormones.
A compound which inhibits or antagonises the biosynthesis or actions of estrogens.
Biologically active substance whose activity affects or plays a role in the functioning of the immune system.
A drug used to treat allergic reactions.
4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)vinyl]benzoic acid
p-(1-(5,6,7,8-Tetrahydro-3,5,5,8,8-pentamethyl-2-naphthyl)vinyl)benzoic acid
Any molecular entity that contains carbon.
An agent which overcomes insulin resistance by activation of the peroxisome proliferator activated receptor gamma (PPAR-gamma).
A role played by a chemical compound to induce direct or indirect DNA damage. Such damage can potentially lead to the formation of a malignant tumour, but DNA damage does not lead inevitably to the creation of cancerous cells.
A role played by a chemical compound which is known to induce a process of carcinogenesis by corrupting normal cellular pathways, leading to the acquistion of tumoral capabilities.
A chemical compound which causes the onset of an allergic reaction by interacting with any of the molecular pathways involved in an allergy.
A chemical compound, or part thereof, which causes the onset of an allergic reaction by interacting with any of the molecular pathways involved in an allergy.
A role played by a chemical compound in biological systems with adverse consequences in embryo developments, leading to birth defects, embryo death or altered development, growth retardation and functional defect.
A role played by a chemical compound exihibiting itself through the ability to induce damage to the liver in animals.
A role played by an entity exihibiting itself through the ability to induce damage to the liver in animals.
A role played by aan entity exihibiting itself through the ability to induce damage to the heart and cardiomyocytes.
A member of the class of phenylureas that is urea in which one of the nitrogens is substituted by a 4-chloro-3-trifluorophenyl group while the other is substituted by a phenyl group which, in turn, is substituted at the para position by a [2-(methylcarbamoyl)pyridin-4-yl]oxy group.
An EC 2.7.11.* (protein-serine/threonine kinase) inhibitor that interferes with the action of non-specific serine/threonine protein kinase (EC 2.7.11.1), a kinase enzyme involved in phosphorylation of hydroxy group of serine or threonine.
ATP-protein transphosphorylase inhibitor
ATP-protein transphosphorylase inhibitors
ATP:protein phosphotransferase (non-specific) inhibitor
ATP:protein phosphotransferase (non-specific) inhibitors
BR serine/threonine-protein kinase 2 inhibitor
BR serine/threonine-protein kinase 2 inhibitors
EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitors
cAMP-dependent protein kinase A inhibitor
cAMP-dependent protein kinase A inhibitors
cAMP-dependent protein kinase inhibitors
cGMP-dependent protein kinase inhibitors
calcium/phospholipid-dependent protein kinase inhibitor
calcium/phospholipid-dependent protein kinase inhibitors
casein kinase (phosphorylating) inhibitor
casein kinase (phosphorylating) inhibitors
cyclic AMP-dependent protein kinase A inhibitor
cyclic AMP-dependent protein kinase A inhibitors
cyclic AMP-dependent protein kinase inhibitor
cyclic AMP-dependent protein kinase inhibitors
cyclic monophosphate-dependent protein kinase inhibitor
cyclic monophosphate-dependent protein kinase inhibitors
cyclic nucleotide-dependent protein kinase inhibitor
cyclic nucleotide-dependent protein kinase inhibitors
non-specific serine/threonine protein kinase (EC 2.7.11.1) inhibitor
non-specific serine/threonine protein kinase (EC 2.7.11.1) inhibitors
non-specific serine/threonine protein kinase inhibitor
non-specific serine/threonine protein kinase inhibitors
phosphorylase b kinase kinase inhibitors
protein kinase (phosphorylating) inhibitor
protein kinase (phosphorylating) inhibitors
protein serine-threonine kinase inhibitor
protein serine-threonine kinase inhibitors
protein-serine/threonine kinase inhibitors
ribosomal protein S6 kinase II inhibitor
ribosomal protein S6 kinase II inhibitors
serine(threonine) protein kinase inhibitor
serine(threonine) protein kinase inhibitors
serine-specific protein kinase inhibitor
serine-specific protein kinase inhibitors
serine/threonine protein kinase inhibitor
serine/threonine protein kinase inhibitors
threonine-specific protein kinase inhibitor
threonine-specific protein kinase inhibitors
EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor
An agent that modulates the physiologic angiogenesis process. This is accomplished by endogenous angiogenic proteins and a variety of other chemicals and pharmaceutical agents.
A compound that specifically inhibits the reuptake of serotonin in the brain. This increases the serotonin concentration in the synaptic cleft which then activates serotonin receptors to a greater extent.
A fatty acyl-CoA that results from the formal condensation of the thiol group of coenzyme A with the carboxy group of any unsaturated fatty acid.
A dopaminergic agent that blocks the transport of dopamine into axon terminals or into storage vesicles within terminals. Most of the adrenergic uptake inhibitors also inhibit dopamine uptake.
A drug that modulates the function of the endocrine glands, the biosynthesis of their secreted hormones, or the action of hormones upon their specific sites.
A role played by the molecular entity or part thereof within a chemical context.
Testosterone, 9-fluoro-11beta-hydroxy-17-methyl-
A drug used to produce muscle relaxation (excepting neuromuscular blocking agents). Its primary clinical and therapeutic use is the treatment of muscle spasm and immobility associated with strains, sprains, and injuries of the back and, to a lesser degree, injuries to the neck. Also used for the treatment of a variety of clinical conditions that have in common only the presence of skeletal muscle hyperactivity, for example, the muscle spasms that can occur in multiple sclerosis.
A drug used for its actions on skeletal muscle.
A substance, such as agonists, antagonists, degradation or uptake inhibitors, depleters, precursors, and modulators of receptor function, used for its pharmacological actions on GABAergic systems.
4-(1,1-Dimethylethyl)-N-(6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-(2,2'-bipyrimidin)-4-yl) benzenesulfornamide
A hormone antagonist that blocks endothelin receptors.
A biological role played by the molecular entity or part thereof within a biochemical context.
A role played by the molecular entity or part thereof which causes the development of a pathological process.
A biological role which describes how a drug interacts within a biological system and how the interactions affect its medicinal properties.
Any molecule or ion capable of binding to a central metal atom to form coordination complexes.
Any substance introduced into a living organism with therapeutic or diagnostic purpose.
A chemical substance that encourages a cell to commence cell division, triggering mitosis.
An EC 3.2.* (glycosylase) inhibitor that interferes with the action of any glycosidase (i.e. enzymes hydrolysing O- and S-glycosyl compounds, EC 3.2.1.*).
An inhibitor of ribonuclease H (EC 3.1.26.13), an enzyme required for specific hydrolysis of the RNA strand of an RNA/DNA hybrid.
EC 3.1.26.13 (retroviral ribonuclease H) inhibitors
retroviral reverse transcriptase RNaseH inhibitor
retroviral reverse transcriptase RNaseH inhibitors
retroviral ribonuclease H (EC 3.1.26.13) inhibitor
retroviral ribonuclease H (EC 3.1.26.13) inhibitors
EC 3.1.26.13 (retroviral ribonuclease H) inhibitor
L-Phenylalaninamide substituted at the amide nitrogen by a 1-(dihydroxyboranyl)-3-methylbutyl group and at N(alpha) by a pyrazin-2-ylcarbonyl group. It is a dipeptidyl boronic acid that reversibly inhibits the 26S proteasome.
[(1R)-3-methyl-1-({(2S)-3-phenyl-2-[(pyrazin-2-ylcarbonyl)amino]propanoyl}amino)butyl]boronic acid
A drug that blocks the action of proteasomes, cellular complexes that break down proteins.
5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid
2,2-Dimethyl-5-(2,5-xylyloxy)valeric acid
A topoisomerase inhibitor that inhibits DNA topoisomerase IV, which catalyses ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands.
An entity which inhibits the activity of HIV-1 reverse transcriptase.
A drug that suppresses spasms. These are usually caused by smooth muscle contraction, especially in tubular organs. The effect is to prevent spasms of the stomach, intestine or urinary bladder.
A drug used for its effects on the gastrointestinal system, e.g. controlling gastric acidity, regulating gastrointestinal motility and water flow, and improving digestion.
A semisynthetic echinocandin anti-fungal drug. It is active against Aspergillus and Candida species and is used for the treatment of invasive candidiasis.
A dialdehyde that is propane substituted by two oxo groups at the terminal carbon atoms respectively. A biomarker of oxidative damage to lipids caused by smoking, it exists in vivo mainly in the enol form.
A naphthoquinone compound having a 4-(4-chlorophenyl)cyclohexyl group at the 2-position and a hydroxy substituent at the 3-position.
A monocarboxylic acid that is propionic acid in which one of the hydrogens at position 2 is substituted by a 4-(2-methylpropyl)phenyl group.
2-[4-(2-methylpropyl)phenyl]propanoic acid
Any substance that stimulates an immune response in the body, such as through antibody production or by presentation to a T-cell receptor after binding to a major histocompability complex (MHC).
Any EC 3.4.* (hydrolases acting on peptide bond) inhibitor that inhibits the activity of a serine endopeptidase (EC 3.4.21.*).
EC 3.4.21.* (serine endopeptidase) inhibitors
inhibitor of serine endopeptidase (EC 3.4.21.*)
inhibitor of serine endopeptidase (EC 3.4.21.*)s
EC 3.4.21.* (serine endopeptidase) inhibitor
An EC 1.14.13.* (oxidoreductase acting on paired donors, incorporating 1 atom of oxygen, with NADH or NADPH as one donor) inhibitor that interferes with the action of squalene monooxygenase (EC 1.14.13.132).
EC 1.14.13.132 (squalene monooxygenase) inhibitors
squalene monooxygenase (EC 1.14.13.132) inhibitor
squalene monooxygenase (EC 1.14.13.132) inhibitors
EC 1.14.13.132 (squalene monooxygenase) inhibitor
Any substance that inhibits the synthesis of DNA.
A reagent that forms a bond to its reaction partner (the nucleophile) by accepting both bonding electrons from that reaction partner.
A reagent that forms a bond to its reaction partner (the electrophile) by donating both bonding electrons.
A drug which interferes with the binding, fusion and entry of an HIV virion to a human cell. By blocking this step in HIV's replication cycle, such agents slow the progression from HIV infection to AIDS.
A DNA polymerase inhibitor that interferes with the activity of reverse transcriptase, EC 2.7.7.49, a viral DNA polymerase enzyme that retroviruses need in order to reproduce.
DNA nucleotidyltransferase (RNA-directed) inhibitor
DNA nucleotidyltransferase (RNA-directed) inhibitors
EC 2.7.7.49 (RNA-directed DNA polymerase) inhibitors
RNA-dependent deoxyribonucleate nucleotidyltransferase inhibitor
RNA-dependent deoxyribonucleate nucleotidyltransferase inhibitors
RNA-directed DNA polymerase (EC 2.7.7.49) inhibitor
RNA-directed DNA polymerase (EC 2.7.7.49) inhibitors
RNA-instructed DNA polymerase inhibitors
deoxynucleoside-triphosphate:DNA deoxynucleotidyltransferase (RNA-directed) inhibitor
deoxynucleoside-triphosphate:DNA deoxynucleotidyltransferase (RNA-directed) inhibitors
EC 2.7.7.49 (RNA-directed DNA polymerase) inhibitor
A cyclic hexapeptide echinocandin antibiotic which exerts its effect by inhibiting the synthesis of 1,3-beta-D-glucan, an integral component of the fungal cell wall. It is used as the sodium salt for the treatment of invasive candidiasis, and of aspergillosis in patients who are intolerant of other therapy.
5-[(1S,2S)-2-{(2R,6S,9S,11R,12R,14aS,15S,16S,20S,23S,25aS)-20-[(1R)-3-amino-1-hydroxy-3-oxopropyl]-2,11,12,15-tetrahydroxy-6-[(1R)-1-hydroxyethyl]-16-methyl-5,8,14,19,22,25-hexaoxo-9-[(4-{5-[4-(pentyloxy)phenyl]isoxazol-3-yl}benzoyl)amino]tetracosahydro-1H-dipyrrolo[2,1-c:2',1'-l][1,4,7,10,13,16]hexaazacyclohenicosin-23-yl}-1,2-dihydroxyethyl]-2-hydroxyphenyl hydrogen sulfate
A derivative of phosphatidylinositol in which the inositol ring is phosphorylated at three unspecified positions.
A hydrolase inhibitor that interferes with the action of any hydrolase acting on peptide bonds (peptidase), EC 3.4.*.*).
EC 3.4.* (hydrolase acting on peptide bond) inhibitor
EC 3.4.* (hydrolase acting on peptide bonds) inhibitors
EC 3.4.* (hydrolases acting on peptide bond) inhibitors
inhibitor of hydrolases acting on peptide bond (EC 3.4.*)
inhibitors of hydrolases acting on peptide bond (EC 3.4.*)
EC 3.4.* (hydrolases acting on peptide bond) inhibitor
A carbohydrazide obtained by formal condensation between pyridine-4-carboxylic acid and hydrazine.
A retinoic acid that is all-trans-retinoic acid in which the double bond which is alpha,beta- to the carboxy group is isomerised to Z configuration. A synthetic retinoid, it is used for the treatment of severe cases of acne and other skin diseases.
(2Z,4E6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoic acid
An N-arylpiperazine that is cis-ketoconazole in which the imidazol-1-yl group is replaced by a 1,2,4-triazol-1-yl group and in which the actyl group attached to the piperazine moiety is replaced by a p-[(+-)1-sec-butyl-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl]phenyl group. A potent P-glycoprotein and CYP3A4 inhibitor, it is used as an antifungal drug for the treatment of various fungal infections, including aspergillosis, blastomycosis, candidiasis, chromoblastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, and sporotrichosis.
Any substance which inhibits the action of receptors for excitatory amino acids.
excitatory amino acid receptor antagonist
excitatory amino acid receptor antagonists
A lysophosphatidic acid having the unusual property of a phosphodiester moiety linked to positions sn-1 and sn1' of glycerol; and two additional fatty acids esterified to the glycerol head group.
BMP is a negatively charged phospholipid found almost exclusively in late endosomes/lysosomes. BMP content is higher in alveolar macrophages (18% of total phospholipids) than in other cell types. BMP is a structural isomer of phosphatidylglycerol (PG) and is synthesized through a series of acylation and deacylation steps involving a transacylase. BMP its unusual sn-1;sn-1′ structural configuration (based on the phosphate-linked glycerol carbon), which is not observed in other phospholipids. This unusual configuration is thought to play a role in the resistance of BMP to many phospholipases, and its stability in late endosomes/lysosomes. BMP stimulates the degradation of glycosphingolipids in coordination with lipid binding proteins (saposins) in lysosomes. PMID:25795792
bis(monoacylglycerol) hydrogen phosphate
Any substance that interacts with tubulin to inhibit or promote polymerisation of microtubules.
A poison that interferes with the function of the kidneys.
An EC 3.5.1.* (non-peptide linear amide C-N hydrolase) inhibitor that interferes with the function of histone deacetylase (EC 3.5.1.98).
EC 3.5.1.98 (histone deacetylase) inhibitors
histone deacetylase (EC 3.5.1.98) inhibitor
histone deacetylase (EC 3.5.1.98) inhibitors
EC 3.5.1.98 (histone deacetylase) inhibitor
Any organic molecular entity derived from a fatty acid.
A fatty acyl-CoA in which the fatty acyl group has a chain length greater than C22.
Any substance that interacts with tubulin to inhibit polymerisation of microtubules.
An EC 2.7.10.* (protein-tyrosine kinase) inhibitor that interferes with the action of receptor protein-tyrosine kinase (EC 2.7.10.1).
ATP:[protein]-L-tyrosine O-phosphotransferase (receptor-type) inhibitor
ATP:[protein]-L-tyrosine O-phosphotransferase (receptor-type) inhibitors
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitors
ephrin-B3 receptor tyrosine kinase inhibitor
insulin receptor protein-tyrosine kinase inhibitor
neurite outgrowth regulating kinase inhibitor
novel oncogene with kinase-domain inhibitor
receptor protein tyrosine kinase inhibitor
receptor protein-tyrosine kinase (EC 2.7.10.1) inhibitor
receptor protein-tyrosine kinase (EC 2.7.10.1) inhibitors
receptor protein-tyrosine kinase inhibitor
receptor protein-tyrosine kinase inhibitors
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor
An EC 1.2.3.* (oxidoreductase acting on donor aldehyde/oxo group with oxygen as acceptor) inhibitor which interferes with the action of aldehyde oxidase (EC 1.2.3.1).
EC 1.2.3.1 (aldehyde oxidase) inhibitors
aldehyde oxidase (EC 1.2.3.1) inhibitors
aldehyde:oxygen oxidoreductase inhibitor
aldehyde:oxygen oxidoreductase inhibitors
An EC 2.4.2.* (pentosyltransferase) inhibitor that interferes with the action of purine nucleoside phosphorylase (EC 2.4.2.1).
EC 2.4.2.1 (purine-nucleoside phosphorylase) inhibitors
inosine-guanosine phosphorylase inhibitor
inosine-guanosine phosphorylase inhibitors
purine deoxynucleoside phosphorylase inhibitor
purine deoxynucleoside phosphorylase inhibitors
purine deoxyribonucleoside phosphorylase inhibitor
purine deoxyribonucleoside phosphorylase inhibitors
purine nucleoside phosphorylase inhibitor
purine nucleoside phosphorylase inhibitors
purine ribonucleoside phosphorylase inhibitor
purine ribonucleoside phosphorylase inhibitors
purine-nucleoside phosphorylase (EC 2.4.2.1) inhibitor
purine-nucleoside phosphorylase (EC 2.4.2.1) inhibitors
purine-nucleoside phosphorylase inhibitor
purine-nucleoside phosphorylase inhibitors
purine-nucleoside:phosphate ribosyltransferase inhibitor
purine-nucleoside:phosphate ribosyltransferase inhibitors
EC 2.4.2.1 (purine-nucleoside phosphorylase) inhibitor
The element or compound in a reduction-oxidation (redox) reaction that donates an electron to another species.
A substance that removes electrons from another reactant in a redox reaction.
A secondary amino compound formally derived from ammonia by replacing two of the hydrogens by 2-(3-carbamoyl-4-hydroxyphenyl)-2-hydroxyethyl and 4-phenylbutan-2-yl groups. It is an adrenergic antagonist used to treat high blood pressure.
3-Carboxamido-4-hydroxy-alpha-((1-methyl-3-phenylpropylamino)methyl)benzyl alcohol
A nucleoside analogue obtained by formal dehydration across positions 2 and 3 of thymidine. An inhibitor of HIV-1 reverse transcriptase
An aminopyrimidine that consists of 2,6-diaminopyrimidine bearing a bromo substituent at position 5, a 4-cyano-2,6-dimethylphenoxy substituent at position 4 and having a 4-cyanophenyl substituent attached to the 2-amino group. NNRTI of HIV-1, binds directly to RT and blocks RNA-dependent and DNA-dependent DNA polymerase activities
An optically active form of ofloxacin having (S)-configuration; an inhibitor of bacterial topoisomerase IV and DNA gyrase
(3S)-9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid
(3S)-(-)-9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid
(S)-(-)-9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzooxazine-6-carboxylic acid
(S)-9-Fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido(1,2,3-de)-1,4-benzoxazine-6-carboxylic acid
A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 4,4-difluorocyclohexanecarboxylic acid and the primary amino group of (1S)-3-[(3-exo)-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]oct-8-yl]-1-phenylpropylamine. An antiretroviral drug, it prevents the interaction of HIV-1 gp120 and chemokine receptor 5 (CCR5) necessary for CCR5-tropic HIV-1 to enter cells.
A dipyridodiazepine that is 5,11-dihydro-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepine which is substituted by methyl, oxo, and cyclopropyl groups at positions 4, 6, and 11, respectively. A non-nucleoside reverse transcriptase inhibitor with activity against HIV-1, it is used in combination with other antiretrovirals for the treatment of HIV infection.
A pyridine-2-sulfonamide substituted at C-5 by a trifluoromethyl group and at the sulfonamide nitrogen by a dihydropyrone-containing m-tolyl substituent. It is an HIV-1 protease inhibitor.
2,1,3-Benzothiadiazole substituted at C-4 by a Delta(1)-imidazolin-2-ylamino group and at C-4 by a chloro group. It is an agonist at alpha2-adrenergic receptor sites.
Benzophenone substituted on one of the phenyl rings at C-3 and C-4 by hydroxy groups and at C-5 by a nitro group, and on the other phenyl ring by a methyl group at C-4. It is an inhibitor of catechol O-methyltransferase.
A member of the class of 1,2,4-triazines in which the triazene skeleton is substituted by amino groups at positions 3 and 5, and by a 2,3-dichlorophenyl group at position 6.
An antogonist that blocks chemokine receptor 5 (CCR5).
Any compound that can be used for the treatment of neurodegenerative disorders.
A macrolide that is 13,19-didehydrosenecionan bearing two additional hydroxy substituents at positions 12 and 18 as well as two additional oxo groups at positions 11 and 16.
An agonist that selectively binds to and activates a protein kinase C receptor
A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 5-methyl-1,2-oxazole-4-carboxylic acid with the anilino group of 4-(trifluoromethyl)aniline. The prodrug of teriflunomide.
5-Methylisoxazole-4-carboxylic acid (4-trifluoromethyl)anilide
An agonist that selectively binds to and activates a protein kinase receptor.
Any chemical substance produced during the conversion of a reactant to a product.
An N-arylpiperazine that consists of piperazine carrying two 4-substituted phenyl groups at positions 1 and 4. A triazole antifungal drug.
A neurotransmitter transporter modulator that activates glutamate transporters.
excitatory amino-acid transporter activator
excitatory amino-acid transporter activators
A membrane transport modulator that affects the transport of neurotransmitters.
A glycerophosphocholine that is glycero-3-phosphocholine bearing two acyl substituents at positions 1 and 2.
Any of a class of phospholipids in which the amino group of a sphingoid base is in amide linkage with one of several fatty acids, while the terminal hydroxy group of the sphingoid base is esterified to phosphorylcholine.
Any substance that causes disturbance to organisms by chemical reaction or other activity on the molecular scale, when a sufficient quantity is absorbed by the organism.
Any compound that inhibits cell division (mitosis).
A drug used to treat or prevent infections caused by Mycobacteria, a genus of actinobacteria. Aerobic and nonmotile, members of the genus include the pathogens responsible for causing tuberculosis and leprosy.
An antiparasitic drug which is effective against Apicomplexan parasites in the genus Plasmodium. The genus contains over 200 species and includes those responsible for malaria.
Any protease inhibitor that restricts the action of a serine protease.
An antiviral agent that destroys or inhibits the replication of the human immunodeficiency virus.
An anti-HIV agent that destroys or inhibits the replication of HIV-1, the more infective and more virulent of the two types of HIV virus.
A clathrate complex consisting of a lipid enwrapped in a protein host without covalent binding in such a way that the complex has a hydrophilic outer surface consisting of all the protein and the polar ends of any phospholipids.
A lipoxygenase inhibitor that interferes with the action of arachidonate 5-lipoxygenase (EC 1.13.11.34).
EC 1.13.11.34 (arachidonate 5-lipoxygenase) inhibitors
arachidonate 5-lipoxygenase (EC 1.13.11.34) inhibitor
arachidonate 5-lipoxygenase (EC 1.13.11.34) inhibitors
arachidonic acid 5-lipoxygenase inhibitor
arachidonic acid 5-lipoxygenase inhibitors
EC 1.13.11.34 (arachidonate 5-lipoxygenase) inhibitor
Any EC 3.1.1.* (carboxylic ester hydrolase) inhibitor that inhibits the action of triacylglycerol lipase (EC 3.1.1.3).
EC 3.1.1.3 (triacylglycerol lipase) inhibitors
heparin releasable hepatic lipase inhibitor
heparin releasable hepatic lipase inhibitors
hepatic monoacylglycerol acyltransferase inhibitor
hepatic monoacylglycerol acyltransferase inhibitors
pancreatic triacylglycerol lipase inhibitor
pancreatic triacylglycerol lipase inhibitors
post-heparin plasma protamine-resistant lipase inhibitor
post-heparin plasma protamine-resistant lipase inhibitors
salt-resistant post-heparin lipase inhibitor
salt-resistant post-heparin lipase inhibitors
triacylglycerol ester hydrolase inhibitor
triacylglycerol ester hydrolase inhibitors
triacylglycerol lipase (EC 3.1.1.3) inhibitor
triacylglycerol lipase (EC 3.1.1.3) inhibitors
EC 3.1.1.3 (triacylglycerol lipase) inhibitor
Any compound that has anti-asthmatic effects.
A member of the class of azetidines that is melagatran in which the carboxylic acid group has been converted to the corresponding ethyl ester and in which the amidine group has been converted into the corresponding amidoxime. A prodrug for melagatran, ximelagatran was the first orally available direct thrombin inhibitor to be brought to market as an anticoagulant, but was withdrawn in 2006 following reports of it causing liver damage.
ethyl N-{(1R)-1-cyclohexyl-2-[(2S)-2-{[4-(N'-hydroxycarbamimidoyl)benzyl]carbamoyl}azetidin-1-yl]-2-oxoethyl}glycinate
ethyl 2-[[(1R)-1-cyclohexyl-2- [(2S)-2-[[4-(N'-hydroxycarbamimidoyl) phenyl]methylcarbamoyl]azetidin-1-yl]- 2-oxo-ethyl]amino]acetate
Antipsychotic drugs which can have different modes of action but which tend to be less likely than first generation antipsychotics to cause extrapyramidal motor control disabilities such as body rigidity or Parkinson's disease-type movements.
An antagonist at the vascular endothelial growth factor receptor.
vascular endothelial growth factor receptor antagonists
vascular endothelial growth factor receptor inhibitor
vascular endothelial growth factor receptor inhibitors
vascular endothelial growth factor receptor antagonist
An EC 3.4.21.* (serine endopeptidase) inhibitor that interferes with the action of thrombin (EC 3.4.21.5).
activated blood-coagulation factor II inhibitor
activated blood-coagulation factor II inhibitors
A compound that inhibits the action of gamma-aminobutyric acid.
gamma-aminobutyric acid receptor antagonist
gamma-aminobutyric acid receptor antagonists
Any compound which can be used to treat or alleviate the symptoms of dyskinesia.
Any compound which inhibits the postganglionic functioning of the sympathetic nervous system (SNS).
Any compound used to suppress premature labour and immature birth by suppressing uterine contractions.
A chemosterilant intended to sterilize insects.
A ryanodine receptor modulator which activates the receptor. Ryanodine receptors (RyRs) act as selective ion channels, modulating the release of calcium. Activating the receptors causes the release of calcium, so depleting internal calcium and ultimately preventing further muscle contraction.
An aminobenzoic acid that is anthranilic acid in which one of the hydrogens attached to the nitrogen is replaced by a 2,3-dimethylphenyl group. Although classed as a non-steroidal anti-inflammatory drug, its anti-inflammatory properties are considered to be minor. It is used to relieve mild to moderate pain, including headaches, dental pain, osteoarthritis and rheumatoid arthritis.
2-[(2,3-dimethylphenyl)amino]benzoic acid
An antogonist that interferes with the action of activator protein 1 (AP-1).
An EC 3.2.1.* (glycosidase) inhibitor that interferes with the action of alpha-glucosidase (EC 3.2.1.20).
EC 3.2.1.20 (alpha-glucosidase) inhibitors
alpha-glucosidase (EC 3.2.1.20) inhibitor
alpha-glucosidase (EC 3.2.1.20) inhibitors
EC 3.2.1.20 (alpha-glucosidase) inhibitor
A benzothiazine that is piroxicam in which the pyridin-2-yl group is replaced by a 5-methyl-1,3-thiazol-2-yl group. A non-steroidal anti-inflammatory drug and selective inhibitor of COX-2, it is used particularly for the management of rheumatoid arthritis.
4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide
A purine nucleoside analogue consisting of a 6-amino-2-chloropurin-9-yl group attached to the 1beta position of 2'-deoxy-2'-fluoro-D-arabinofuranose. It is metabolized intracellularly to the active 5'-triphosphate metabolite, which inhibits DNA synthesisis and so stops the growth of cancer cells. Clofarabine is used as an antimetabolite antineoplastic agent in the treatment of relapsed or refractory acute lymphoblastic leukaemia.
Any substance that inhibits the process of apoptosis (programmed cell death) in multi-celled organisms.
Any substance that induces the process of apoptosis (programmed cell death) in multi-celled organisms.
A maleate ester resulting from the formal condensation of both carboxy groups of maleic acid with ethanol. A colourless liquid at room temperature (m.p. -10degreeC) with boiling point 220degreeC at 1 atm., it is commonly used as a dienophile for Diels-Alder-type cycloaddition reactions in organic synthesis.
A compound which causes a reduction in the levels of glutathione in cells.
An EC 1.3.98.* (oxidoreductase acting on CH-CH group of donors, with other, known, acceptors) inhibitor that interferes with the action of dihydroorotate oxidase (fumarate), EC 1.3.98.1 (formerly EC 1.3.3.1).
(S)-dihydroorotate:fumarate oxidoreductase inhibitor
(S)-dihydroorotate:fumarate oxidoreductase inhibitors
EC 1.3.98.1 (dihydroorotate oxidase (fumarate)) inhibitor
EC 1.3.98.1 (dihydroorotate oxidase (fumarate)) inhibitors
EC 1.3.98.1 [dihydroorotate oxidase (fumarate)] inhibitors
dihydroorotate oxidase (fumarate) (EC 1.3.98.1) inhibitor
dihydroorotate oxidase (fumarate) (EC 1.3.98.1) inhibitors
dihydroorotate oxidase (fumarate) inhibitor
dihydroorotate oxidase (fumarate) inhibitors
EC 1.3.98.1 [dihydroorotate oxidase (fumarate)] inhibitor
A pathway inhibitor that inhibits the synthesis of pyrimidine.
purinergic receptor subtype P2Y12 antagonist
purinergic receptor subtype P2Y12 antagonists
An aromatic ether which is 2,6-dimethylphenyl ether of 2-aminopropan-1-ol.
An EC 5.99.1.* (miscellaneous isomerase) inhibitor that interferes with the action of any of the topoisomerases (enzymes that regulate the overwinding or underwinding of DNA).
A PPAR modulator which activates the peroxisome proliferator-activated receptor-alpha.
peroxisome proliferator-activated receptor-alpha agonist
A pyrimidine that is 5-(pyrimidin-2-yl}amino-2-methylbenzenesulfonamide substituted at position 4 by a (2,3-dimethylindazol-6-yl)(methyl)amino group. Used as its hydrochloride salt for treatment of kidney cancer.
An enzyme inhibitor that inhibits the action of a transferase (EC 2.*)
An imidazolidine-2,4-dione that is hydantoin substituted at position 1 by a [(5-nitro-2-furyl)methylene]amino group. An antibiotic that damages bacterial DNA.
An EC 2.3.1.* (acyltransferase transferring other than amino-acyl group) inhibitor that interferes with the action of fatty acid synthase (EC 2.3.1.85), a multi-enzyme protein involved in fatty acid synthesis.
EC 2.3.1.85 (fatty acid synthase) inhibitors
acyl-CoA:malonyl-CoA C-acyltransferase (decarboxylating, oxoacyl- and enoyl-reducing and thioester-hydrolysing) inhibitor
acyl-CoA:malonyl-CoA C-acyltransferase (decarboxylating, oxoacyl- and enoyl-reducing and thioester-hydrolysing) inhibitors
fatty acid synthase (EC 2.3.1.85) inhibitor
fatty acid synthase (EC 2.3.1.85) inhibitors
EC 2.3.1.85 (fatty acid synthase) inhibitor
A PPAR modulator which activates the peroxisome proliferator-activated receptor-gamma.
peroxisome proliferator-activated receptor-gamma agonist
Any molecule that consists of at least one carbon atom as part of the electrically neutral entity.
An agonist that binds to and activates aryl hydrocarbon receptors (AhRs).
An amino acid that is phenylacetic acid which is substituted at position 2 by the nitrogen of 2-chloro-6-fluoroaniline and at position 5 by a methyl group. A highly selective cyclooxygenase 2 inhibitor, it was briefly used for the treatment of osteoarthritis, but was withdrawn due to concersns of hepatotoxicity.
{2-[(2-chloro-6-fluorophenyl)amino]-5-methylphenyl}acetic acid
2-((2-chloro-6-fluorophenyl)amino)-5-methylbenzeneacetic acid
Any hydrolase inhibitor that interferes with the action of a hydrolase which acts on acid anhydrides (EC 3.6.*.*).
EC 3.6.* (hydrolases acting on acid anhydrides) inhibitors
inhibitor of hydrolase acting on acid anhydride (EC 3.6.*)
inhibitors of hydrolase acting on acid anhydride (EC 3.6.*)
EC 3.6.* (hydrolases acting on acid anhydrides) inhibitor
An inhibitor of NF-kappaB (nuclear factor kappa-light-chain-enhancer of activated B cells), a protein complex involved in the transcription of DNA.
nuclear factor kappa-light-chain-enhancer of activated B cells inhibitor
nuclear factor kappa-light-chain-enhancer of activated B cells inhibitors
A carbonyl compound produced as a water-soluble byproduct when fatty acids are broken down for energy in the liver. There are three endogenous ketone bodies: acetone, acetoacetic acid, and (R)-3-hydroxybutyric acid; others may be produced as a result of the metabolism of synthetic triglycerides.
An antimetabolite that impairs the action of folic acids
An EC 1.17.* (oxidoreductase acting on CH or CH2) inhibitor that inhibits the action of ribonucleoside-diphosphate reductase (EC 1.17.4.1).
2'-deoxyribonucleoside-diphosphate:thioredoxin-disulfide 2'-oxidoreductase inhibitor
2'-deoxyribonucleoside-diphosphate:thioredoxin-disulfide 2'-oxidoreductase inhibitors
EC 1.17.4.1 (ribonucleoside-diphosphate reductase) inhibitors
nucleoside diphosphate reductase inhibitor
nucleoside diphosphate reductase inhibitors
ribonucleoside diphosphate reductase inhibitor
ribonucleoside diphosphate reductase inhibitors
ribonucleoside-diphosphate reductase (EC 1.17.4.1) inhibitor
ribonucleoside-diphosphate reductase (EC 1.17.4.1) inhibitors
ribonucleoside-diphosphate reductase inhibitor
ribonucleoside-diphosphate reductase inhibitors
ribonucleotide diphosphate reductase inhibitor
ribonucleotide diphosphate reductase inhibitors
EC 1.17.4.1 (ribonucleoside-diphosphate reductase) inhibitor
An antagonist at the epidermal growth factor receptor.
epidermal growth factor receptor antagonists
epidermal growth factor receptor inhibitor
epidermal growth factor receptor inhibitors
epidermal growth factor receptor antagonist
Any substance which is used to reduce or control weight.
A 3-oxo Delta(4)-steroid that is estr-4-en-3-one substituted by a beta-hydroxy group at position 17.
An aryl sulfide that is used (as its mesylate salt) for treatment of HIV and also exhibits some anticancer properties.
A tripeptide that is L-leucyl-L-leucyl-L-leucine in which the C-terminal carboxy group has been reduced to the corresponding aldehyde and the N-terminal amino group is protected as its benzyloxycarbonyl derivative.
An enzyme inhibitor that inhibits the action of an isomerase (EC 5.*.*.*).
Nilutamide, sold under the brand names Nilandron and Anandron, is a nonsteroidal antiandrogen (NSAA) which is used in the treatment of prostate cancer. (by Wikipedia)
Any metabolite produced during a metabolic reaction in eukaryotes, the taxon that include members of the fungi, plantae and animalia kingdoms.
Any eukaryotic metabolite produced during a metabolic reaction in animals that include diverse creatures from sponges, insects to mammals.
Any animal metabolite produced during a metabolic reaction in mammals.
Any mammalian metabolite produced during a metabolic reaction in a mouse (Mus musculus).
Any metabolite produced during a metabolic reaction in prokaryotes, the taxon that include members of domains such as the bacteria and archaea.
A monocarboxylic acid that is propionic acid substituted at position 2 by a 2-(4-chlorophenyl)-1,3-benzoxazol-5-yl group. It was used as a non-steroidal anti-inflammatory drug until 1982 when it was withdrawn from the market due to adverse side-effects including liver necrosis, photosensitivity, and carcinogenicity in animals.
2-[2-(4-chlorophenyl)-1,3-benzoxazol-5-yl]propanoic acid
(1)-2-(4-Chlorophenyl)benzoxazole-5-propionic acid
2-(4-Chlorophenyl)-alpha-methyl-5-benzoxazoleacetic acid
2-(p-chlorophenyl)-alpha-methyl-5-benzoxazoleacetic acid
An organic heterotricyclic compound that is 2H,5H-[1,3]oxazino[5,6-c][1,2]benzothiazine-2,4(3H)-dione 6,6-dioxide substituted at positions 3 and 5 by pyridin-2-yl and methyl groups respectively. A prodrug of piroxicam, it is used for the relief of pain and inflammation in musculoskeletal disorders such as rheumatoid arthritis and osteoarthritis.
5-methyl-3-(pyridin-2-yl)-2H,5H-[1,3]oxazino[5,6-c][1,2]benzothiazine-2,4(3H)-dione 6,6-dioxide
A monocarboxylic acid that is acetic acid in which one of the methyl hydrogens is replaced by a 4-isobutylphenyl group. Although it was shown to be effective in treatment of rheumatoid arthritis, the clinical use of ibufenac was discontinued due to hepatotoxic side-effects.
Any metabolite produced by metabolism of a xenobiotic compound.
An organic tricyclic compound that is 10,11-dihydro-5H-dibenzo[a,d][7]annulene substituted by a 3-(methylamino)propylidene group at position 5. It is an active metabolite of amitriptyline.
A bridged organochlorine compound resulting from the Diels-Alder reaction of hexachlorocyclopentadiene with maleic anhydride followed by hydrolysis of the resulting anhydride. A chemical intermediate used in the preparation of fire-retardant polyester resins and plasticisers.
1,4,5,6,7,7-hexachlorobicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic acid
A transferase inhibitor inhibiting the action of transferase of a one-carbon-containing group (EC 2.1.*.*).
one-carbon-containing group transferase inhibitor
one-carbon-containing group transferase inhibitors
A transferase inhibitor that interferes with the action of an acyltransferase (EC 2.3.*.*).
A transferase inhibitor inhibiting the action of a glycosyltransferase (EC 2.4.*.*).
EC 2.4.* (glycosyltransferase) inhibitors
glycosyltransferase (EC 2.4.*) inhibitor
glycosyltransferase (EC 2.4.*) inhibitors
EC 2.4.* (glycosyltransferase) inhibitor
A transferase inhibitor that inhibits the transfer of an alkyl (other than methyl) or aryl group (EC 2.5.1.*).
EC 2.5.1.* (non-methyl-alkyl or aryl transferase) inhibitors
alkyl/aryl (non-methyl) transferase inhibitor
alkyl/aryl (non-methyl) transferase inhibitors
non-methyl alkyl/aryl transferase (EC 2.5.1.*) inhibitor
non-methyl alkyl/aryl transferase (EC 2.5.1.*) inhibitors
non-methyl alkyl/aryl transferase inhibitor
non-methyl alkyl/aryl transferase inhibitors
non-methyl-alkyl or aryl transferase inhibitor
non-methyl-alkyl or aryl transferase inhibitors
EC 2.5.1.* (non-methyl-alkyl or aryl transferase) inhibitor
A transferase inhibitor that inhibits the action of a phosphorus-containing group transferase (EC 2.7.*.*).
EC 2.7.* (P-containing group transferase) inhibitors
EC 2.7.* (phosphorus-containing group transferase) inhibitor
EC 2.7.* (phosphorus-containing group transferase) inhibitors
phosphorus-containing group transferase (EC 2.7.*) inhibitor
phosphorus-containing group transferase (EC 2.7.*) inhibitors
phosphorus-containing group transferase inhibitor
phosphorus-containing group transferase inhibitors
EC 2.7.* (P-containing group transferase) inhibitor
An isomerase inhibitor that interferes with the action of any member of the group of 'other isomerases' (EC 5.99.*.*).
EC 5.99.* (miscellaneous isomerases) inhibitor
EC 5.99.* (miscellaneous isomerases) inhibitors
An enzyme inhibitor which interferes with the action of a lyase (EC 4.*.*.*). Lyases are enzymes cleaving C-C, C-O, C-N and other bonds by other means than by hydrolysis or oxidation.
A lyase inhibitor which inhibits the action of a C-O lyase (EC 4.2.*.*).
An enzyme inhibitor which interferes with the action of an oxidoreductase (EC 1.*.*.*).
An oxidoreductase inhibitor which interferes with the action of an oxidoreductase acting on the CH-OH group of donors (EC 1.1.*.*).
EC 1.1.* (oxidoreductase acting on donor CH-OH group) inhibitors
inhibitor of oxidoreductase acting on CH-OH group of donor
inhibitor of oxidoreductase acting on CH-OH group of donors
inhibitors of oxidoreductase acting on CH-OH group of donor
inhibitors of oxidoreductase acting on CH-OH group of donors
oxidoreductase acting on donor CH-OH group (EC 1.1.*) inhibitor
oxidoreductase acting on donor CH-OH group (EC 1.1.*) inhibitors
oxidoreductase acting on donor CH-OH group inhibitor
oxidoreductase acting on donor CH-OH group inhibitors
EC 1.1.* (oxidoreductase acting on donor CH-OH group) inhibitor
An oxidoreductase inhibitor which interferes with the action of an oxidoreductase acting on the aldehyde or oxo group of donors (EC 1.2.*.*).
EC 1.2.* (oxidoreductase acting on donor aldehyde or oxo group) inhibitor
EC 1.2.* (oxidoreductase acting on donor aldehyde or oxo group) inhibitors
EC 1.2.* (oxidoreductase acting on donor aldehyde/oxo group) inhibitors
inhibitor of oxidoreductase acting on aldehyde or oxo group of donor
inhibitor of oxidoreductase acting on aldehyde or oxo group of donors
inhibitor of oxidoreductase acting on aldehyde/oxo group of donor
inhibitor of oxidoreductase acting on aldehyde/oxo group of donors
inhibitors of oxidoreductase acting on aldehyde or oxo group of donor
inhibitors of oxidoreductase acting on aldehyde or oxo group of donors
inhibitors of oxidoreductase acting on aldehyde/oxo group of donor
inhibitors of oxidoreductase acting on aldehyde/oxo group of donors
oxidoreductase acting on donor aldehyde or oxo group (EC 1.2.*) inhibitor
oxidoreductase acting on donor aldehyde or oxo group (EC 1.2.*) inhibitors
oxidoreductase acting on donor aldehyde or oxo group inhibitor
oxidoreductase acting on donor aldehyde or oxo group inhibitors
oxidoreductase acting on donor aldehyde/oxo group (EC 1.2.*) inhibitor
oxidoreductase acting on donor aldehyde/oxo group (EC 1.2.*) inhibitors
oxidoreductase acting on donor aldehyde/oxo group inhibitor
oxidoreductase acting on donor aldehyde/oxo group inhibitors
EC 1.2.* (oxidoreductase acting on donor aldehyde/oxo group) inhibitor
An oxidoreductase inhibitor which interferes with the action of an oxidoreductase acting on the CH-CH group of donors (EC 1.3.*.*).
EC 1.3.* (oxidoreductase acting on donor CH-CH group) inhibitors
inhibitor of oxidoreductase acting on CH-CH group of donor
inhibitor of oxidoreductase acting on CH-CH group of donors
inhibitors of oxidoreductase acting on CH-CH group of donor
inhibitors of oxidoreductase acting on CH-CH group of donors
oxidoreductase acting on donor CH-CH group (EC 1.3.*) inhibitor
oxidoreductase acting on donor CH-CH group (EC 1.3.*) inhibitors
oxidoreductase acting on donor CH-CH group inhibitor
oxidoreductase acting on donor CH-CH group inhibitors
EC 1.3.* (oxidoreductase acting on donor CH-CH group) inhibitor
An oxidoreductase inhibitor which interferes with the action of an oxidoreductase acting on the CH-NH group of donors (EC 1.5.*.*).
EC 1.5.* (oxidoreductase acting on donor CH-NH group) inhibitors
inhibitor of oxidoreductase acting on CH-NH group of donor
inhibitor of oxidoreductase acting on CH-NH group of donors
inhibitors of oxidoreductase acting on CH-NH group of donor
inhibitors of oxidoreductase acting on CH-NH group of donors
oxidoreductase acting on donor CH-NH group (EC 1.5.*) inhibitor
oxidoreductase acting on donor CH-NH group (EC 1.5.*) inhibitors
EC 1.5.* (oxidoreductase acting on donor CH-NH group) inhibitor
An oxidoreductase inhibitor which interferes with the action of an oxidoreductase acting on NADH or NADPH (EC 1.6.*.*).
EC 1.6.* (oxidoreductase acting on NADH or NADPH) inhibitors
inhibitor of oxidoreductase acting on NADH or NADPH
inhibitor of oxidoreductase acting on NADH or NADPH (EC 1.6.*)
inhibitors of oxidoreductase acting on NADH or NADPH
inhibitors of oxidoreductase acting on NADH or NADPH (EC 1.6.*)
oxidoreductase acting on NADH or NADPH (EC 1.6.*) inhibitor
oxidoreductase acting on NADH or NADPH (EC 1.6.*) inhibitors
oxidoreductase acting on NADH or NADPH inhibitor
oxidoreductase acting on NADH or NADPH inhibitors
EC 1.6.* (oxidoreductase acting on NADH or NADPH) inhibitor
An oxidoreductase inhibitor which interferes with the action of an oxidoreductase of class EC 1.8.*.* (acting on a sulfur group of donors).
EC 1.8.* (oxidoreductase acting on sulfur group of donors) inhibitors
oxidoreductase acting on a sulfur group of donors (EC 1.8.*) inhibitor
oxidoreductase acting on a sulfur group of donors (EC 1.8.*) inhibitors
EC 1.8.* (oxidoreductase acting on sulfur group of donors) inhibitor
An oxidoreductase inhibitor which interferes with the action of an oxidoreductase acting on diphenols and related substances as donors (EC 1.10.*.*).
EC 1.10.* (oxidoreductase acting on diphenols and related substances as donors) inhibitors
EC 1.10.* (oxidoreductases acting on diphenols and related substances as donors) inhibitor
EC 1.10.* (oxidoreductases acting on diphenols and related substances as donors) inhibitors
inhibitor of an oxidoreductase acting on diphenols and related substances as donor
inhibitor of an oxidoreductase acting on diphenols and related substances as donor (EC 1.10.*)
inhibitor of an oxidoreductase acting on diphenols and related substances as donors
inhibitors of an oxidoreductase acting on diphenols and related substances as donor
inhibitors of an oxidoreductase acting on diphenols and related substances as donor (EC 1.10.*)
inhibitors of an oxidoreductase acting on diphenols and related substances as donors
EC 1.10.* (oxidoreductase acting on diphenols and related substances as donors) inhibitor
An oxidoreductase inhibitor which interferes with the action of an oxidoreductase acting on single donors with incorporation of molecular oxygen (oxygenases), EC 1.13.*.*.
EC 1.13.* [oxidoreductase acting on single donors with incorporation of molecular oxygen (oxygenases)] inhibitors
oxidoreductase acting on single donors with incorporation of molecular oxygen (oxygenases) (EC 1.13.*) inhibitor
oxidoreductase acting on single donors with incorporation of molecular oxygen (oxygenases) (EC 1.13.*) inhibitors
oxidoreductase acting on single donors with incorporation of molecular oxygen (oxygenases) inhibitor
oxidoreductase acting on single donors with incorporation of molecular oxygen (oxygenases) inhibitors
EC 1.13.* [oxidoreductase acting on single donors with incorporation of molecular oxygen (oxygenases)] inhibitor
An oxidoreductase inhibitor which interferes with the action of an oxidoreductase acting on hydrogen as donors (EC 1.14.*.*).
EC 1.14.* (oxidoreductase acting on paired donors, with incorporation or reduction of molecular oxygen) inhibitors
inhibitor of oxidoreductase acting on paired donors, with incorporation or reduction of molecular oxygen (EC 1.14.*)
inhibitor of oxidoreductases acting on paired donors, with incorporation or reduction of molecular oxygen (EC 1.14.*)
inhibitors of oxidoreductase acting on paired donors, with incorporation or reduction of molecular oxygen (EC 1.14.*)
inhibitors of oxidoreductases acting on paired donors, with incorporation or reduction of molecular oxygen (EC 1.14.*)
oxidoreductase acting on paired donors, with incorporation or reduction of molecular oxygen (EC 1.14.*) inhibitor
oxidoreductase acting on paired donors, with incorporation or reduction of molecular oxygen (EC 1.14.*) inhibitors
oxidoreductase acting on paired donors, with incorporation or reduction of molecular oxygen inhibitor
oxidoreductase acting on paired donors, with incorporation or reduction of molecular oxygen inhibitors
EC 1.14.* (oxidoreductase acting on paired donors, with incorporation or reduction of molecular oxygen) inhibitor
An oxidoreductase inhibitor which interferes with the action of an oxidoreductase acting on CH or CH2 (EC 1.17.*.*).
EC 1.17.* (oxidoreductase acting on CH or CH2) inhibitors
oxidoreductase acting on CH or CH2 (EC 1.17.*) inhibitor
oxidoreductase acting on CH or CH2 (EC 1.17.*) inhibitors
oxidoreductase acting on CH or CH2 inhibitor
oxidoreductase acting on CH or CH2 inhibitors
EC 1.17.* (oxidoreductase acting on CH or CH2) inhibitor
Any enzyme inhibitor that interferes with the action of a hydrolase (EC 3.*.*.*).
A hydrolase inhibitor that interferes with the action of any ester hydrolase (EC 3.1.*.*).
A hydrolase inhibitor that interferes with the action of any glycosylase (EC 3.2.*.*).
Any hydrolase inhibitor that interferes with the action of a hydrolase acting on C-N bonds, other than peptide bonds (EC 3.5.*.*).
EC 3.5.* (hydrolase acting on non-peptide C-N bond) inhibitor
EC 3.5.* (hydrolase acting on non-peptide C-N bond) inhibitors
EC 3.5.* (hydrolases acting on C-N bonds, other than peptide bonds) inhibitor
EC 3.5.* (hydrolases acting on C-N bonds, other than peptide bonds) inhibitors
EC 3.5.* (hydrolases acting on non-peptide C-N bonds) inhibitors
EC 3.5.* (hydrolases acting on non-peptide C-N bonds) inhibitor
An EC 3.1.* (ester hydrolase) inhibitor that interferes with the action of a carboxylic ester hydrolase (EC 3.1.1.*).
EC 3.1.1.* (carboxylic ester hydrolase) inhibitors
carboxylic ester hydrolase (EC 3.1.1.*) inhibitor
carboxylic ester hydrolase (EC 3.1.1.*) inhibitors
EC 3.1.1.* (carboxylic ester hydrolase) inhibitor
An EC 3.1.* (ester hydrolase) inhibitor that interferes with the action of any phosphoric monoester hydrolase (EC 3.1.3.*).
EC 3.1.3.* (phosphoric monoester hydrolase) inhibitors
inhibitor of phosphoric monoester hydrolase
inhibitor of phosphoric monoester hydrolase (EC 3.1.3.*)
inhibitors of phosphoric monoester hydrolase
inhibitors of phosphoric monoester hydrolase (EC 3.1.3.*)
phosphoric monoester hydrolase (EC 3.1.3.*) inhibitor
phosphoric monoester hydrolase (EC 3.1.3.*) inhibitors
phosphoric monoester hydrolase inhibitor
phosphoric monoester hydrolase inhibitors
EC 3.1.3.* (phosphoric monoester hydrolase) inhibitor
Any EC 3.4.21.* (serine endopeptidase) inhibitor that interferes with the action of prolyl oligopeptidase (EC 3.4.21.26).
EC 3.4.21.26 (prolyl oligopeptidase) inhibitors
proline-specific endopeptidase inhibitor
proline-specific endopeptidase inhibitors
prolyl oligopeptidase (EC 3.4.21.26) inhibitor
prolyl oligopeptidase (EC 3.4.21.26) inhibitors
EC 3.4.21.26 (prolyl oligopeptidase) inhibitor
An EC 3.1.* (ester hydrolase) inhibitor that interferes with the action of any endoribonuclease producing 5'-phosphomonoesters (EC 3.1.26.*).
EC 3.1.26.* (endoribonucleases producing 5'-phosphomonoesters) inhibitors
endoribonuclease producing 5'-phosphomonoesters (EC 3.1.26.*) inhibitor
endoribonuclease producing 5'-phosphomonoesters (EC 3.1.26.*) inhibitors
endoribonuclease producing 5'-phosphomonoesters inhibitor
endoribonuclease producing 5'-phosphomonoesters inhibitors
EC 3.1.26.* (endoribonucleases producing 5'-phosphomonoesters) inhibitor
An EC 2.4.* (glycosyltransferase) inhibitor that interferes with the action of any pentosyltransferase (EC 2.4.2.*).
EC 2.4.2.* (pentosyltransferase) inhibitors
pentosyltransferase (EC 2.4.2.*) inhibitor
pentosyltransferase (EC 2.4.2.*) inhibitors
EC 2.4.2.* (pentosyltransferase) inhibitor
An EC 2.5.1.* (non-methyl-alkyl or aryl transferase) inhibitor that interferes with the action of a glutathione transferase (EC 2.5.1.18).
EC 2.5.1.18 (glutathione transferase) inhibitors
S-(hydroxyalkyl)glutathione lyase inhibitor
S-(hydroxyalkyl)glutathione lyase inhibitors
glutathione S-alkyl transferase inhibitor
glutathione S-alkyl transferase inhibitors
glutathione S-alkyltransferase inhibitor
glutathione S-alkyltransferase inhibitors
glutathione S-aralkyltransferase inhibitor
glutathione S-aralkyltransferase inhibitors
glutathione S-aryltransferase inhibitors
glutathione transferase (EC 2.5.1.18) inhibitor
glutathione transferase (EC 2.5.1.18) inhibitors
EC 2.5.1.18 (glutathione transferase) inhibitor
An EC 3.5.* (hydrolases acting on non-peptide C-N bonds) inhibitor that interferes with the action of any non-peptide linear amide C-N hydrolase (EC 3.5.1.*).
EC 3.5.1.* (non-peptide linear amide C-N hydrolase) inhibitors
non-peptide linear amide C-N hydrolase (EC 3.5.1.*) inhibitor
non-peptide linear amide C-N hydrolase (EC 3.5.1.*) inhibitors
EC 3.5.1.* (non-peptide linear amide C-N hydrolase) inhibitor
An EC 3.1.4.* (phosphoric diester hydrolase) inhibitor that interferes with the action of sphingomyelin phosphodiesterase (EC 3.1.4.12).
EC 3.1.4.12 (sphingomyelin phosphodiesterase) inhibitor
sphingomyelin phosphodiesterase inhibitor
sphingomyelin phosphodiesterase inhibitor role
An EC 2.7.* (P-containing group transferase) inhibitor that interferes with the action of any protein-serine/threonine kinase (EC 2.7.11.*).
EC 2.7.11.* (protein-serine/threonine kinase) inhibitors
protein-serine/threonine kinase (EC 2.7.11.*) inhibitor
protein-serine/threonine kinase (EC 2.7.11.*) inhibitors
protein-serine/threonine kinase inhibitor
EC 2.7.11.* (protein-serine/threonine kinase) inhibitor
An EC 2.7.* (P-containing group transferase) inhibitor that interferes with the action of any nucleotidyltransferase (EC 2.7.7.*).
EC 2.7.7.* (nucleotidyltransferase) inhibitors
inhibitor of nucleotidyltransferases (EC 2.7.7.*)
inhibitors of nucleotidyltransferases (EC 2.7.7.*)
nucleotidyltransferase (EC 2.7.7.*) inhibitor
nucleotidyltransferase (EC 2.7.7.*) inhibitors
EC 2.7.7.* (nucleotidyltransferase) inhibitor
An EC 2.7.* (P-containing group transferase) inhibitor that interferes with the action of any protein-tyrosine kinase (EC 2.7.10.*).
EC 2.7.10.* (protein-tyrosine kinase) inhibitors
protein-tyrosine kinase (EC 2.7.10.*) inhibitor
protein-tyrosine kinase (EC 2.7.10.*) inhibitors
EC 2.7.10.* (protein-tyrosine kinase) inhibitor
An EC 5.99.* (other isomerases) inhibitor that interferes with the activity of any enzyme in the EC 5.99.1.* class.
EC 5.99.1.* (miscellaneous isomerase) inhibitors
EC 5.99.1.* (miscellaneous isomerase) inhibitor
An EC 2.5.* (transferase) inhibitor that inhibits the action of any transferase that transfers an alkyl (other than methyl) or aryl group (EC 2.5.*).
EC 2.5.* (non-methyl-alkyl or aryl transferase) inhibitors
non-methyl-alkyl or aryl transferase (EC 2.5.*) inhibitor
non-methyl-alkyl or aryl transferase (EC 2.5.*) inhibitors
EC 2.5.* (non-methyl-alkyl or aryl transferase) inhibitor
An EC 1.1.* (oxidoreductase acting on donor CH-OH group) inhibitor that uses NAD(+) or NADP(+) as acceptor (EC 1.1.1.*).
EC 1.1.1.* (oxidoreductase acting on donor CH-OH group, NAD(+) or NADP(+)acceptor) inhibitors
oxidoreductase acting on donor CH-OH group, NAD(+) or NADP(+) acceptor (EC 1.1.1.*) inhibitor
oxidoreductase acting on donor CH-OH group, NAD(+) or NADP(+) acceptor (EC 1.1.1.*) inhibitors
EC 1.1.1.* (oxidoreductase acting on donor CH-OH group, NAD(+) or NADP(+) acceptor) inhibitor
An EC 1.13.* [oxidoreductase acting on single donors with incorporation of molecular oxygen (oxygenases)] inhibitor that inhibits the action of any oxidoreductase incorporating 2 atoms of oxygen (EC 1.13.11.*).
EC 1.13.11.* (oxidoreductase acting on single donors and incorporating 2 O atoms) inhibitors
EC 1.13.11.* (oxidoreductase acting on single donors and incorporating 2 atoms of oxygen) inhibitor
EC 1.13.11.* (oxidoreductase acting on single donors and incorporating 2 atoms of oxygen) inhibitors
oxidoreductase acting on single donors and incorporating 2 atoms of oxygen (EC 1.13.11.*) inhibitor
oxidoreductase acting on single donors and incorporating 2 atoms of oxygen (EC 1.13.11.*) inhibitors
EC 1.13.11.* (oxidoreductase acting on single donors and incorporating 2 O atoms) inhibitor
An EC 1.14.* (oxidoreductase acting on paired donors, with incorporation or reduction of molecular oxygen) inhibitor that interferes with the action of any such enzyme incorporating one atom of oxygen and using reduced flavin or flavoprotein as donor (EC 1.14.14.*).
EC 1.14.14.* (oxidoreductase acting on paired donors, incorporating of 1 atom of oxygen, with reduced flavin or flavoprotein as one donor) inhibitors
EC 1.14.14.* (oxidoreductase acting on paired donors, with incorporation of 1 atom of oxygen, with reduced flavin or flavoprotein as one donor) inhibitor
EC 1.14.14.* (oxidoreductase acting on paired donors, with incorporation of 1 atom of oxygen, with reduced flavin or flavoprotein as one donor) inhibitors
oxidoreductase acting on paired donors, with incorporation of 1 atom of oxygen, with reduced flavin or flavoprotein as one donor (EC 1.14.14.*) inhibitor
oxidoreductase acting on paired donors, with incorporation of 1 atom of oxygen, with reduced flavin or flavoprotein as one donor (EC 1.14.14.*) inhibitors
EC 1.14.14.* (oxidoreductase acting on paired donors, incorporating of 1 atom of oxygen, with reduced flavin or flavoprotein as one donor) inhibitor
An EC 1.14.* (oxidoreductase acting on paired donors, with incorporation or reduction of molecular oxygen) inhibitor that interferes with the action of any enzyme in the EC 1.14.99.* (miscellaneous) category.
EC 1.14.99.* (miscellaneous oxidoreductase acting on paired donors, with incorporation or reduction of molecular oxygen) inhibitors
miscellaneous oxidoreductase acting on paired donors, with incorporation or reduction of molecular oxygen (EC 1.14.99.*) inhibitor
miscellaneous oxidoreductase acting on paired donors, with incorporation or reduction of molecular oxygen (EC 1.14.99.*) inhibitors
EC 1.14.99.* (miscellaneous oxidoreductase acting on paired donors, with incorporation or reduction of molecular oxygen) inhibitor
An EC 1.14.* (oxidoreductase acting on paired donors, with incorporation or reduction of molecular oxygen) inhibitor that interferes with the action of any such enzyme incorporating one atom of oxygen and using NADH or NADPH as one donor (EC 1.14.13.*).
EC 1.14.13.* (oxidoreductase acting on paired donors, incorporating 1 atom of oxygen, with NADH or NADPH as one donor) inhibitors
oxidoreductase acting on paired donors, incorporating 1 atom of oxygen, with NADH or NADPH as one donor (EC 1.14.13.*) inhibitor
oxidoreductase acting on paired donors, incorporating 1 atom of oxygen, with NADH or NADPH as one donor (EC 1.14.13.*) inhibitors
EC 1.14.13.* (oxidoreductase acting on paired donors, incorporating 1 atom of oxygen, with NADH or NADPH as one donor) inhibitor
An EC 1.17.* (oxidoreductase acting on CH or CH2) inhibitor that interferes with the activity of any such enzyme that uses a disulfide as acceptor (EC 1.17.4.*).
EC 1.17.4.* (oxidoreductase acting on CH or CH2 with a disulfide as acceptor) inhibitors
oxidoreductase acting on CH or CH2 with a disulfide as acceptor (EC 1.17.4.*) inhibitor
oxidoreductase acting on CH or CH2 with a disulfide as acceptor (EC 1.17.4.*) inhibitors
EC 1.17.4.* (oxidoreductase acting on CH or CH2 with a disulfide as acceptor) inhibitor
An EC 1.17.* (oxidoreductase acting on CH or CH2) inhibitor that interferes with the function of any such enzyme that uses oxygen as acceptor (EC 1.17.3.*).
EC 1.17.3.* (oxidoreductase acting on CH or CH2 with oxygen as acceptor) inhibitors
oxidoreductase acting on CH or CH2 with oxygen as acceptor (EC 1.17.3.*) inhibitor
oxidoreductase acting on CH or CH2 with oxygen as acceptor (EC 1.17.3.*) inhibitors
EC 1.17.3.* (oxidoreductase acting on CH or CH2 with oxygen as acceptor) inhibitor
An EC 1.2.* (oxidoreductase acting on donor aldehyde/oxo group) inhibitor that interferes with the action of any such enzyme using NAD(+) or NADP(+) as acceptor (EC 1.2.1.*).
EC 1.2.1.* (oxidoreductase acting on donor aldehyde/oxo group with NAD(+) or NADP(+) as acceptor) inhibitors
oxidoreductase acting on donor aldehyde/oxo group with NAD(+) or NADP(+) as acceptor (EC 1.2.1.*) inhibitor
oxidoreductase acting on donor aldehyde/oxo group with NAD(+) or NADP(+) as acceptor (EC 1.2.1.*) inhibitors
EC 1.2.1.* (oxidoreductase acting on donor aldehyde/oxo group with NAD(+) or NADP(+) as acceptor) inhibitor
An EC 1.2.* (oxidoreductase acting on donor aldehyde/oxo group) inhibitor that interferes with the action of any such enzyme using oxygen as acceptor (EC 1.2.3.*).
EC 1.2.3.* (oxidoreductase acting on donor aldehyde/oxo group with oxygen as acceptor) inhibitors
oxidoreductase acting on donor aldehyde/oxo group with oxygen as acceptor (EC 1.2.3.*) inhibitor
oxidoreductase acting on donor aldehyde/oxo group with oxygen as acceptor (EC 1.2.3.*) inhibitors
EC 1.2.3.* (oxidoreductase acting on donor aldehyde/oxo group with oxygen as acceptor) inhibitor
An EC 1.3.* (oxidoreductase acting on donor CH-CH group) inhibitor that interferes with the function of any such enzyme in the EC 1.3.98.* (with other, known, acceptors) category.
EC 1.3.98.* (oxidoreductase acting on CH-CH group of donors, with other, known, acceptors) inhibitor
EC 1.3.98.* (oxidoreductase acting on CH-CH group of donors, with other, known, acceptors) inhibitors
EC 1.3.98.* (oxidoreductase acting on donor CH-CH group, with other, known, acceptors) inhibitors
oxidoreductase acting on CH-CH group of donors, with other, known, acceptors (EC 1.3.98.*) inhibitor
oxidoreductase acting on CH-CH group of donors, with other, known, acceptors (EC 1.3.98.*) inhibitors
EC 1.3.98.* (oxidoreductase acting on donor CH-CH group, with other, known, acceptors) inhibitor
An EC 1.5.* (oxidoreductase acting on donor CH-NH group) inhibitor that interferes with the action of any such enzyme using NAD(+) or NADP(+) as acceptor (EC 1.5.1.*).
EC 1.5.1.* (oxidoreductase acting on donor CH-NH group, NAD(+) or NADP(+) as acceptor) inhibitors
oxidoreductase acting on donor CH-NH group, NAD(+) or NADP(+) as acceptor (EC 1.5.1.*) inhibitor
oxidoreductase acting on donor CH-NH group, NAD(+) or NADP(+) as acceptor (EC 1.5.1.*) inhibitors
EC 1.5.1.* (oxidoreductase acting on donor CH-NH group, NAD(+) or NADP(+) as acceptor) inhibitor
An EC 1.6.* (oxidoreductase acting on NADH or NADPH) inhibitor that interferes with the action of any such enzyme using a quinone or similar as acceptor (EC 1.6.5.*).
EC 1.6.5.* (oxidoreductase acting on NADH or NADPH with a quinone or similar as acceptor) inhibitors
oxidoreductase acting on NADH or NADPH with a quinone or similar as acceptor (EC 1.6.5.*) inhibitor
oxidoreductase acting on NADH or NADPH with a quinone or similar as acceptor (EC 1.6.5.*) inhibitors
EC 1.6.5.* (oxidoreductase acting on NADH or NADPH with a quinone or similar as acceptor) inhibitor
An EC 1.8.* (oxidoreductase acting on sulfur group of donors) inhibitor that interferes with the action of any such enzyme using NAD(+) or NADP(+) as acceptor (EC 1.8.1.*).
EC 1.8.1.* (oxidoreductase acting on sulfur group of donors, NAD(+) or NADP(+) as acceptor) inhibitors
oxidoreductase acting on sulfur group of donors, NAD(+) or NADP(+) as acceptor (EC 1.8.1.*) inhibitor
oxidoreductase acting on sulfur group of donors, NAD(+) or NADP(+) as acceptor (EC 1.8.1.*) inhibitors
EC 1.8.1.* (oxidoreductase acting on sulfur group of donors, NAD(+) or NADP(+) as acceptor) inhibitor
An EC 2.1.* (C1-transferase) inhibitor that interferes with the action of any methyltransferase (EC 2.1.1.*).
EC 2.1.1.* (methyltransferase) inhibitor
EC 2.1.1.* (methyltransferase) inhibitors
EC 2.1.1.* (methyltransferases) inhibitors
methyltransferase (EC 2.1.1.*) inhibitor
methyltransferase (EC 2.1.1.*) inhibitors
EC 2.1.1.* (methyltransferases) inhibitor
An EC 2.3.* (acyltransferase) inhibitor that inhibits the action of any acyltransferase transferring groups other than amino-acyl groups (EC 2.3.1.*).
EC 2.3.1.* (acyltransferase transferring other than amino-acyl group) inhibitors
acyltransferase transferring other than amino-acyl group EC 2.3.1.* inhibitor
acyltransferase transferring other than amino-acyl group EC 2.3.1.* inhibitors
EC 2.3.1.* (acyltransferase transferring other than amino-acyl group) inhibitor
An EC 3.6.* (hydrolases acting on acid anhydrides) inhibitor that interferes with the action of any such enzyme that catalyses transmembrane movement of substances (EC 3.6.3.*).
EC 3.6.3.* (acid anhydride hydrolase catalysing transmembrane movement of substances) inhibitors
acid anhydride hydrolase catalysing transmembrane movement of substances (EC 3.6.3.*) inhibitor
acid anhydride hydrolase catalysing transmembrane movement of substances (EC 3.6.3.*) inhibitors
EC 3.6.3.* (acid anhydride hydrolase catalysing transmembrane movement of substances) inhibitor
An EC 1.14.14.* (oxidoreductase acting on paired donors, incorporating of 1 atom of oxygen, with reduced flavin or flavoprotein as one donor) inhibitor that interferes with the action of an unspecified monooxygenase (EC 1.14.14.1).
EC 1.14.14.1 (unspecific monooxygenase) inhibitors
flavoprotein-linked monooxygenase inhibitor
flavoprotein-linked monooxygenase inhibitors
substrate,reduced-flavoprotein:oxygen oxidoreductase (RH-hydroxylating or -epoxidising) inhibitor
substrate,reduced-flavoprotein:oxygen oxidoreductase (RH-hydroxylating or -epoxidising) inhibitors
unspecific monooxygenase (EC 1.14.14.1) inhibitor
unspecific monooxygenase (EC 1.14.14.1) inhibitors
EC 1.14.14.1 (unspecific monooxygenase) inhibitor
An EC 4.2.* (C-O lyase) inhibitor that interferes with the action of any hydro-lyase (EC 4.2.1.*).
An enzyme inhibitor that interferes with one or more steps in a metabolic pathway.
An enzyme inhibitor that interferes with one or more steps in a signaling or metabolic pathway.
Any eukaryotic metabolite produced during a metabolic reaction in fungi, the kingdom that includes microorganisms such as the yeasts and moulds.
Any fungal metabolite produced during a metabolic reaction in Penicillium.
Any human metabolite produced by metabolism of a xenobiotic compound in humans.
Any prokaryotic metabolite produced during a metabolic reaction in bacteria.
Any bacterial metabolite produced during a metabolic reaction in Escherichia coli.
An antagonist that binds to and inactivates aryl hydrocarbon receptors (AhRs).
An EC 1.3.* (oxidoreductase acting on donor CH-CH group) inhibitor that interferes with the action of any such enzyme using a quinone or related compound as acceptor (EC 1.3.5.*).
EC 1.3.5.* (oxidoreductase acting on CH-CH of donor with a quinone or related compound as acceptor) inhibitors
inhibitor of oxidoreductase acting on CH-CH of donor with a quinone or related compound as acceptor
inhibitor of oxidoreductase acting on CH-CH of donor with a quinone or related compound as acceptor (EC 1.3.5.*)
inhibitors of oxidoreductase acting on CH-CH of donor with a quinone or related compound as acceptor
inhibitors of oxidoreductase acting on CH-CH of donor with a quinone or related compound as acceptor (EC 1.3.5.*)
oxidoreductase acting on CH-CH of donor with a quinone or related compound as acceptor (EC 1.3.5.*) inhibitor
oxidoreductase acting on CH-CH of donor with a quinone or related compound as acceptor (EC 1.3.5.*) inhibitors
EC 1.3.5.* (oxidoreductase acting on CH-CH of donor with a quinone or related compound as acceptor) inhibitor
An EC 1.3.5.* (oxidoreductase acting on CH-CH of donor with a quinone or related compound as acceptor) inhibitor that interferes with the action of dihydroorotate dehydrogenase (quinone), EC 1.3.5.2.
(S)-dihydroorotate:(acceptor) oxidoreductase inhibitor
(S)-dihydroorotate:(acceptor) oxidoreductase inhibitors
(S)-dihydroorotate:acceptor oxidoreductase inhibitor
(S)-dihydroorotate:acceptor oxidoreductase inhibitors
(S)-dihydroorotate:quinone oxidoreductase inhibitor
(S)-dihydroorotate:quinone oxidoreductase inhibitors
EC 1.3.5.2 (dihydroorotate dehydrogenase (quinone)) inhibitor
EC 1.3.5.2 (dihydroorotate dehydrogenase (quinone)) inhibitors
EC 1.3.5.2 [dihydroorotate dehydrogenase (quinone)] inhibitors
dihydroorotate:ubiquinone oxidoreductase inhibitor
dihydroorotate:ubiquinone oxidoreductase inhibitors
EC 1.3.5.2 [dihydroorotate dehydrogenase (quinone)] inhibitor
An EC 1.10.* (oxidoreductase acting on diphenols and related substances as donors) inhibitor that interferes with the action of any such enzyme using a cytochrome as acceptor (EC 1.10.2.*).
EC 1.10.2.* (oxidoreductase acting on diphenols and related substances as donors with a cytochrome as acceptor) inhibitors
inhibitor of an oxidoreductase acting on diphenols and related substances as donors with a cytochrome as acceptor (EC 1.10.2.*)
inhibitors of an oxidoreductase acting on diphenols and related substances as donors with a cytochrome as acceptor (EC 1.10.2.*)
oxidoreductase acting on diphenols and related substances as donors with a cytochrome as acceptor (EC 1.10.2.*) inhibitor
oxidoreductase acting on diphenols and related substances as donors with a cytochrome as acceptor (EC 1.10.2.*) inhibitors
EC 1.10.2.* (oxidoreductase acting on diphenols and related substances as donors with a cytochrome as acceptor) inhibitor
An EC 1.10.2.* (oxidoreductase acting on diphenols and related substances as donors with a cytochrome as acceptor) inhibitor that interferes with the action of quinol--cytochrome-c reductase (EC 1.10.2.2).
EC 1.10.2.2 (quinol--cytochrome-c reductase) inhibitors
inhibitor of quinol--cytochrome-c reductase (EC 1.10.2.2)
inhibitors of quinol--cytochrome-c reductase (EC 1.10.2.2)
quinol--cytochrome-c reductase (EC 1.10.2.2) inhibitor
quinol--cytochrome-c reductase (EC 1.10.2.2) inhibitors
EC 1.10.2.2 (quinol--cytochrome-c reductase) inhibitor
An EC 2.7.11.* (protein-serine/threonine kinase) inhibitor that interferes with the action of IkappaB kinase (EC 2.7.11.10).
ATP:[IkappaB protein] phosphotransferase inhibitor
An agonist that selectively binds to and activates androstane receptors.
constitutive androstane receptor agonist
An EC 1.8.1.* (oxidoreductase acting on sulfur group of donors, NAD+ or NADP+ as acceptor) inhibitor that interferes with the action of trypanothione-disulfide reductase (EC 1.8.1.12).
EC 1.8.1.12 (trypanothione-disulfide reductase) inhibitors
N(1),N(8)-bis(glutathionyl)spermidine reductase inhibitor
N(1),N(8)-bis(glutathionyl)spermidine reductase inhibitors
NADPH2:trypanothione oxidoreductase inhibitor
NADPH2:trypanothione oxidoreductase inhibitors
NADPH:trypanothione oxidoreductase inhibitor
NADPH:trypanothione oxidoreductase inhibitors
trypanothione-disulfide reductase (EC 1.8.1.12) inhibitor
trypanothione-disulfide reductase (EC 1.8.1.12) inhibitors
trypanothione:NADP(+) oxidoreductase inhibitor
trypanothione:NADP(+) oxidoreductase inhibitors
EC 1.8.1.12 (trypanothione-disulfide reductase) inhibitor
A role played by the entity that activates p53.
Any mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
An EC 3.6.3.* (acid anhydride hydrolase catalysing transmembrane movement of substances) inhibitor that interferes with the action of xenobiotic-transporting ATPase (EC 3.6.3.44).
ATP phosphohydrolase (steroid-exporting) inhibitor
ATP phosphohydrolase (steroid-exporting) inhibitors
ATP phosphohydrolase (xenobiotic-exporting) inhibitor
ATP phosphohydrolase (xenobiotic-exporting) inhibitors
EC 3.6.3.44 (xenobiotic-transporting ATPase) inhibitors
pleiotropic-drug-resistance protein inhibitor
pleiotropic-drug-resistance protein inhibitors
xenobiotic-transporting ATPase (EC 3.6.3.44) inhibitor
xenobiotic-transporting ATPase (EC 3.6.3.44) inhibitors
xenobiotic-transporting ATPase inhibitor
xenobiotic-transporting ATPase inhibitors
EC 3.6.3.44 (xenobiotic-transporting ATPase) inhibitor
Any minor or unwanted substance introduced into the environment that can have undesired effects.
Any EC 3.1.1.* (carboxylic ester hydrolase) inhibitor that inhibits the action of carboxylesterase (EC 3.1.1.1 ).
EC 3.1.1.1 (carboxylesterase) inhibitors
A 3-oxo-5alpha- steroid that is 4,5alpha-dihydrotestosterone which is substituted by a hydroxymethylidene group at position 2 and by a methyl group at the 17alpha position. A synthetic androgen, it was mainly used for the treatment of anaemias until being replaced by treatments with fewer side effects.
A steroid glucosiduronic acid that consists of 17β-estradiol having a beta-glucuronyl residue attached at position 17 via a glycosidic linkage.
A member of the class of 1,3-oxazoles that is 1,3-oxazol-4(5H)-one which is substituted by an amino group at position 2 and by a phenyl group at position 5. A central nervous system stimulant, it was used to treat hyperactivity disorders in children, but withdrawn from use following reports of serious hepatotoxicity.
A member of the class of barbiturates, the structure of which is that of barbituric acid substituted at C-5 by ethyl and phenyl groups.
A imidazolidine-2,4-dione that consists of hydantoin bearing two phenyl substituents at position 5.
An animal metabolite produced by arthropods such as crabs, lobsters, crayfish, shrimps and krill.
A Daphnia metabolite produced by the species Daphnia magna.
A crustacean metabolite produced by the genus of small planktonic arthropods, Daphnia
Any compound that inhibits the biosynthesis of any sterol.
Any hepatotoxic agent capable of inducing liver steatosis or fatty liver disease.
A hydrazine in which each nitrogen atom is substituted, one by a 3'-carboxy-2-hydroxy[1,1'-biphenyl]-3-yl group and the other by a 1-(3,4-dimethylphenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene group. A small molecule agonist of the c-mpl (TpoR) receptor (the physiological target of the hormone thrombopoietin), it has been developed as a medication for conditions that lead to thrombocytopenia (abnormally low platelet counts).
3'-{(2Z)-2-[1-(3,4-dimethylphenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene]hydrazinyl}-2'-hydroxy[1,1'-biphenyl]-3-carboxylic acid
3'-{(2Z)-2-[1-(3,4-dimethylphenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene]hydrazino}-2'-hydroxybiphenyl-3-carboxylic acid
An agonist that selectively binds to and activates the thrombopoietin receptor [myeloproliferative leukemia protein or CD110 (Cluster of Differentiation 110)].
Any antifungal agent used to prevent or treat fungal infections in humans or animals.
Any substance used in acriculture, horticulture, forestry, etc. for its fungicidal properties.
Any drug which causes the onset of an allergic reaction.
Any compound that inhibits the process of autophagy (the self-digestion of one or more components of a cell through the action of enzymes originating within the same cell).
A glycerophosphoglycerol resulting from partial hydrolysis of a phosphatidylglycerol, which removes one of the fatty acid groups. The structure is depicted in the image where R1 = acyl, R2 = H or where R1 = H, R2 = acyl.
A drug that acts as an antagonist, agonist, reverse agonist, or in some other fashion when interacting with cellular receptors.
An antagonist at purinergic P2 receptors
An azobenzene consisting of diphenyldiazene having a carboxy substituent at the 4-position, a hydroxy substituent at the 3-position and a 2-pyridylaminosulphonyl substituent at the 4'-position.
2-hydroxy-5-{[4-(pyridin-2-ylsulfamoyl)phenyl]diazenyl}benzoic acid
2-Hydroxy-5-((4-((2-pyridinylamino)sulfonyl)phenyl)azo)benzoic acid
2-Hydroxy-5-[4-(pyridin-2-ylsulfamoyl)-phenylazo]-benzoic acid
5-((p-(2-Pyridylsulfamoyl)phenyl)azo)salicylic acid
5-(4-(2-Pyridylsulfamoyl)phenylazo)-2-hydroxybenzoic acid
5-(p-(2-Pyridylsulfamyl)phenylazo)salicylic acid
A 1,3-thiazole compound having a 4-aminobenzenesulfonamido group at the 2-position.
A monocarboxylic acid that is 1-benzylidene-1H-indene which is substituted at positions 2, 3, and 5 by methyl, carboxymethyl, and fluorine respectively, and in which the phenyl group of the benzylidene moiety is substituted at the para position by a methylsulfinyl group. It is a prodrug for the corresponding sulfide, a non-steroidal anti-inflammatory drug, used particularly in the treatment of acute and chronic inflammatory conditions.
{(1Z)-5-fluoro-2-methyl-1-[4-(methylsulfinyl)benzylidene]-1H-inden-3-yl}acetic acid
(Z)-5-Fluoro-2-methyl-1-((p-(methylsulfinyl)phenyl)methylene)-1H-indene-3-acetic acid
cis-5-Fluoro-2-methyl-1-((4-(methylsulfinyl)phenyl)methylene)-1H-indene-3-acetic acid
cis-5-Fluoro-2-methyl-1-((p-methylsulfinyl)benzylidene)indene-3-acetic acid
A tertiary amine that is N-methyl-1-naphthalenemethylamine in which the amino hydrogen is replaced by a 3-(tertbutylethynyl)allyl group. An antifungal agent administered orally (generally as the hydrochloride salt) for the treatment of skin and nail infections.
(E)-N-(6,6-Dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthalene methanamine
A carboxylic ester resulting from the formal condensation of the carboxy group of N-formyl-L-leucine with the hydroxy group of (3S,4S)-3-hexyl-4-[(2S)-2-hydroxytridecyl]oxetan-2-one. A pancreatic lipase inhibitor, it is used as an anti-obesity drug.
(2S)-1-[(2S,3S)-3-hexyl-4-oxooxetan-2-yl]tridecan-2-yl N-formyl-L-leucinate
(2S)-2-formamido-4-methylpentanoic acid [(2S)-1-[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]tridecan-2-yl] ester
N-formyl-L-leucine (1S)-1-{[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl}dodecyl ester
An organic heterotricyclic compound that is a hexa-oxygenated 6,7-guaianolide isolated fron the roots of Thapsia garganica L., Apiaceae. A potent skin irritant, it is used in traditional medicine as a counter-irritant. Thapsigargin inhibits Ca(2+)-transporting ATPase mediated uptake of calcium ions into sarcoplasmic reticulum and is used in experimentation examining the impacts of increasing cytosolic calcium concentrations.
(3S,3aR,4S,6S,6aR,7S,8S,9bS)-6-(acetyloxy)-4-(butanoyloxy)-3,3a-dihydroxy-3,6,9-trimethyl-8-{[(2Z)-2-methylbut-2-enoyl]oxy}-2-oxo-2,3,3a,4,5,6,6a,7,8,9b-decahydroazuleno[4,5-b]furan-7-yl octanoate
A thienopyridine that is 4,5,6,7-tetrahydrothieno[3,2-c]pyridine in which the hydrogen attached to the nitrogen is replaced by an o-chlorobenzyl group.
Troglitazone is an antidiabetic and anti-inflammatory drug, and a member of the drug class of the thiazolidinediones. It was prescribed for people with diabetes mellitus type 2. (by Wikipedia)
A 1,8-naphthyridine derivative that is 4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid bearing additional 2,4-difluorophenyl, fluoro and 6-amino-3-azabicyclo[3.1.0]hex-3-yl substituents at positions 1, 6 and 7 respectively. A broad-spectrum antibiotic that was withdrawn from the market due to risk of liver failure.
7-[(1R,5S,6s)-6-amino-3-azabicyclo[3.1.0]hex-3-yl]-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid
A bile acid found in the bile of bears (Ursidae) as a conjugate with taurine. Used therapeutically, it prevents the synthesis and absorption of cholesterol and can lead to the dissolution of gallstones.
A cultured cell that is part of a cell line - a stable and homogeneous population of cells with a common biological origin and propagation history in culture
A material entity of anatomical origin (part of or deriving from an organism) that has as its parts a maximally connected cell compartment surrounded by a plasma membrane.
The definition of cell is intended to represent all cells, and thus a cell is defined as a material entity and not an anatomical structure, which implies that it is part of an organism (or the entirety of one).
A cultured cell that is freshly isolated from a organismal source, or derives in culture from such a cell prior to the culture being passaged.
A cell in vitro that is or has been maintained or propagated as part of a cell culture.
A cell that is commited to differentiating into a muscle cell. Embryonic myoblasts develop from the mesoderm. They undergo proliferation, migrate to their various sites, and then differentiate into the appropriate form of myocytes. Myoblasts also occur as transient populations of cells in muscles undergoing repair.
A connective tissue cell which secretes an extracellular matrix rich in collagen and other macromolecules. Flattened and irregular in outline with branching processes; appear fusiform or spindle-shaped.
A cell that is usually found in a two-dimensional sheet with a free surface. The cell has a cytoskeleton that allows for tight cell to cell contact and for cell polarity where apical part is directed towards the lumen and the basal part to the basal lamina.
A type of lymphocyte whose defining characteristic is the expression of a T cell receptor complex.
A tissue-resident macrophage of the reticuloendothelial system found on the luminal surface of the hepatic sinusoids involved in erythrocyte clearance. Markers include F4/80+, CD11b-low, CD68-positive, sialoadhesin-positive, CD163/SRCR-positive. Irregular, with long processes including lamellipodia extending into the sinusoid lumen, have flattened nucleus with cytoplasm containing characteristic invaginations of the plasma membrane (vermiform bodies); lie within the sinusoid lumen attached to the endothelial surface; derived from the bone marrow, form a major part of the body's mononuclear phagocyte system. Markers: Mouse: F4/80+, CD11b-low, CD68+, sialoadhesin+, CD163/SRCR+; role or process: immune, antigen-presentation, clearance of senescent erythrocytes, iron metabolism. Kupffer cells are also reportedly C3aR-positive, CD14-low, CD54-positive, CD88-positive, and CD284-positive. They are also capable of producing IL-1, IL-6, TNF-alpha, nitric oxide, PGD2, PGE2, PGF2alpha, and TXA2.
A leukocyte with abundant granules in the cytoplasm.
A cell that is found in almost all tissues containing numerous basophilic granules and capable of releasing large amounts of histamine and heparin upon activation. Progenitors leave bone marrow and mature in connective and mucosal tissue. Mature mast cells are found in all tissues, except the bloodstream. Their phenotype is CD117-high, CD123-negative, CD193-positive, CD200R3-positive, and FceRI-high. Stem-cell factor (KIT-ligand; SCF) is the main controlling signal of their survival and development.
A fat-storing cell found mostly in the abdominal cavity and subcutaneous tissue of mammals. Fat is usually stored in the form of triglycerides.
A cell that specializes in controlled release of one or more substances.
insulin secreting cell is a secretory cell and is capable of some insulin secretion
Pancreatic beta cells are also reportedly CD284-positive. Upon activation, they upregulate their CD14 expression. A cell that secretes insulin and is located towards the center of the islets of Langerhans.
The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. Majority of cell population of liver, polygonal in shape, arranged in plates or trabeculae between sinusoids; may have single nucleus or binucleated.
A red blood cell. In mammals, mature erythrocytes are biconcave disks containing hemoglobin whose function is to transport oxygen.
A non-nucleated disk-shaped cell formed by extrusion from megakaryocytes, found in the blood of all mammals, and mainly involved in blood coagulation.
Platelets are reportedly CCR1-positive, CCR2-negative, CCR3-positive, CCR4-positive, CCR5-negative, CCR6-negative, CCR7-negative, CCR8-negative, CCR9-negative, CCR10-negative, CD16-positive, CD23-positive, CD32-positive, CD40-positive, CD41-positive CD42-positive, CD61-positive, CD62P-positive, CD64-positive, CD89-positive, CD102-positive, CD147-positive (activated platelets), CD154-positive (activated platelets), CD162-positive, CD209, CD282-positive, CD284-positive, CD289-positive, CD181-negative, CD182-negative, CD183-negative, CD184-positive, CLEC2-positive, GPVI-positive, JAMC-positive, PAR1-positive, PAR2-negative, PAR3-positive, PAR4-positive, TSP1-positive, and TXA2R-positive. Platelets can reportedly produce CCL2, CCL3, CCL5, CCL7, CCL17, CD40L, CXCL1, CXCL4, CXCL4L1, CXCL5, CXCL7, CXCL8, CXCL12, EGF, factor V, factor VII, factor XI, factor XIII, bFGF, histamine, IGF-1, IL-1beta, PAI-1, PDGF, plasminogen, protein S, serotonin, TGF-beta, TFPI, VEGF, and vWF. A non-nucleated disk-shaped cell formed by extrusion from megakaryocytes, found in the blood of all mammals, and mainly involved in blood coagulation.
Any cell capable of ingesting particulate matter via phagocytosis.
A mononuclear phagocyte present in variety of tissues, typically differentiated from monocytes, capable of phagocytosing a variety of extracellular particulate material, including immune complexes, microorganisms, and dead cells.
Morphology: Diameter 30_M-80 _M, abundant cytoplasm, low N/C ratio, eccentric nucleus. Irregular shape with pseudopods, highly adhesive. Contain vacuoles and phagosomes, may contain azurophilic granules; markers: Mouse & Human: CD68, in most cases CD11b. Mouse: in most cases F4/80+; role or process: immune, antigen presentation, & tissue remodelling; lineage: hematopoietic, myeloid.
A lymphocyte of B lineage with the phenotype CD19-positive, CD20-positive, and capable of B cell mediated immunity.
Fat cells with light coloration and few mitochondria. They contain a scant ring of cytoplasm surrounding a single large lipid droplet or vacuole.
A cell from the thermogenic form of adipose tissue found in many species, particularly in newborns and hibernating mammals, but also in lesser amounts in adults of other mammals including humans. Brown fat is capable of rapid liberation of energy and seems to be important in the maintenance of body temperature immediately after birth and upon waking from hibernation.
A cell of hematopoietic origin, typically resident in particular tissues, specialized in the uptake, processing, and transport of antigens to lymph nodes for the purpose of stimulating an immune response via T cell activation. These cells are lineage negative (CD3-negative, CD19-negative, CD34-negative, and CD56-negative).
A lymphocyte is a leukocyte commonly found in the blood and lymph that has the characteristics of a large nucleus, a neutral staining cytoplasm, and prominent heterochromatin.
Myeloid mononuclear recirculating leukocyte that can act as a precursor of tissue macrophages, osteoclasts and some populations of tissue dendritic cells.
A cell in vitro that has undergone physical changes as a consequence of a deliberate and specific experimental procedure.
A cell that is found in the perisinusoidal space of the liver that is capable of multiple roles including storage of retinol, presentation of antigen to T cells (including CD1d-restricted NKT cells), and upon activation, production of extracellular matrix components that can contribute to liver fibrosis. This activated state has a myofibroblast-like phenotype, though it's not clear in the literature if this is terminally differentiated. This cell type comprises approximately 8-15% of total cells in the liver.
An achromatic cell of the myeloid or lymphoid lineages capable of ameboid movement, found in blood or other tissue.
Any of the immature or mature forms of a granular leukocyte that in its mature form has an irregularly shaped, pale-staining nucleus that is partially constricted into two lobes, and with cytoplasm that contains coarse, bluish-black granules of variable size. Basophils contain vasoactive amines such as histamine and serotonin, which are released on appropriate stimulation. A basophil is CD123-positive, CD193-positive, CD203c-positive, and FceRIa-positive.
Any of the immature or mature forms of a granular leukocyte with a nucleus that usually has two lobes connected by one or more slender threads of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and which can be stained by the dye eosin. Eosinophils are CD9-positive, CD191-positive, and CD193-positive.
Any of the immature or mature forms of a granular leukocyte that in its mature form has a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.
A terminally differentiated, post-mitotic, antibody secreting cell of the B cell lineage with the phenotype CD138-positive, surface immunonoglobulin-negative, and MHC Class II-negative. Plasma cells are oval or round with extensive rough endoplasmic reticulum, a well-developed Golgi apparatus, and a round nucleus having a characteristic cartwheel heterochromatin pattern and are devoted to producing large amounts of immunoglobulin.
A T cell that expresses an alpha-beta T cell receptor complex.
A leukocyte with a single non-segmented nucleus in the mature form.
An elicited macrophage that is recruited into the tissues in response to injury and infection as part of an inflammatory response, expresses high levels of pro-inflammatory cytokines, ROS and NO, and shows potent microbicidal activity.
Markers: Express: TNFa, IL1b, IL6, iNOS, NADPH-oxidase; produce: reactive oxygen species, nitric oxide; role or process: immune, inflammation (inflammatory response).
A macrophage constitutively resident in a particular tissue under non-inflammatory conditions, and capable of phagocytosing a variety of extracellular particulate material, including immune complexes, microorganisms, and dead cells.
A type of cell containing lipids in small vacuoles and typically seen in atherolosclerotic lesions, as well as other conditions.
A cell of the supporting or framework tissue of the body, arising chiefly from the embryonic mesoderm and including adipose tissue, cartilage, and bone.
A Niemann-Pick disease characterized by onset in infancy and involvement of neurological tissues that has_material_basis_in an autosomal recessive mutation of SMPD1 on chromosome 11p15.4.
A Niemann-Pick disease characterized by visceral involvement only and survival into adulthood that has_material_basis_in an autosomal recessive mutation of SMPD1 on chromosome 11p15.4.
A Niemann-Pick disease that has_material_basis_in an autosomal recessive mutation of NPC1 on chromosome 18q11.2.
A Niemann-Pick disease that has_material_basis_in an autosomal recessive mutation of NPC2 on chromosome 14q24.3.
A sphingoliidosis characterized by the accumulation of the lipid sphingomyelin in lysosomes in cells.
lipoid histiocytosis (classical phosphatide)
A disease is a disposition (i) to undergo pathological processes that (ii) exists in an organism because of one or more disorders in that organism.
A glucose metabolism disease characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both.
A diabetes mellitus that involves high blood glucose resulting from cells fail to use insulin properly.
A diabetes mellitus that results from the body's failure to produce insulin and has_material_basis_in autoimmune destruction of insulin-producing beta cells of the pancreas.
Substance with antioxidant role is a subtype of substance with role. This entity is participating in a oxidative stress response and playing an antioxidant role.
Substance with role is a subtype of object. This entity is participating in a specific process and playing a role.
In YAMATO ontology theory, an entity (continuant) playing a role in a specific context is called a role holder.
Substance with ligand role is a subtype of substance with role. This entity is participating in signaling and playing a ligand role.
This entity is inferred from Description Logic.
Interacting selectively and non-covalently with acyl-CoA, any derivative of coenzyme A in which the sulfhydryl group is in thiolester linkage with a fatty acyl group.
The division of a mitochondrion within a cell to form two or more separate mitochondrial compartments.
A cell cycle phase during which nuclear division occurs, and which is comprises the phases: prophase, metaphase, anaphase and telophase.
The autophagic process in which mitochondria are delivered to the vacuole and degraded in response to changing cellular conditions.
Degradation of a mitochondrion by macroautophagy.
The selective autophagy process in which a peroxisome is degraded by macroautophagy.
Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating lowered oxygen tension. Hypoxia, defined as a decline in O2 levels below normoxic levels of 20.8 - 20.95%, results in metabolic adaptation at both the cellular and organismal level.
The chemical reactions and pathways involving long-chain fatty acids, A long-chain fatty acid is a fatty acid with a chain length between C13 and C22.
Joining of the large subunit, with release of IF2/eIF2 and IF3/eIF3. This leaves the functional ribosome at the AUG, with the methionyl/formyl-methionyl-tRNA positioned at the P site.
formation of cytoplasmic translation initiation complex
A change in the morphology or behavior of a cell resulting from exposure to an activating factor such as a cellular or soluble ligand.
The expansion of a natural killer cell population by cell division.
The appearance of a cytokine due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels.
Note that this term is intended for use when a gene product is seen to cause apparent increases in intracellular or extracellular cytokine levels, without specific regard as to whether the increase is due to increased biosynthesis, increased secretion of preexisting cytokine molecules, or increased conversion from precursor molecules.
The process that results in the movement of cytochrome c from the mitochondrial intermembrane space into the cytosol, which is part of the apoptotic signaling pathway and leads to caspase activation.
release of cytochrome c from mitochondria
The release of cytochrome c from mitochondria is a central event in the signaling phase of the apoptotic process, and it is often used by researchers to monitor this type of cell death. Any event that induces apoptosis will at some point induce the release of cytochrome c from mitochondria. Therefore, this term should only be used to annotate gene products that are directly involved in this process.
A transition where an epithelial cell loses apical/basolateral polarity, severs intercellular adhesive junctions, degrades basement membrane components and becomes a migratory mesenchymal cell.
The process that results in the fusion of a phagosome, a vesicle formed by phagocytosis, with a lysosome.
The process in which a precursor cell type acquires the specialized features of a NK T cell.
Note that NK T cells are a distinct lineage of T cells expressing natural killer cell markers and having T cell receptors characterized by the usage of a restricted repertoire of variable region gene segments. Note that immunologists typically use the word 'development' to refer to cells of B or T cell lineages undergoing the process that GO describes as 'cell differentiation'.
Any series of molecular signals generated as a consequence of binding to a toll-like receptor. Toll-like receptors directly bind pattern motifs from a variety of microbial sources to initiate innate immune response.
The promotion of an immune response by natural killer cells through direct recognition of target cells or through the release of cytokines.
An immune response based on directed amplification of specific receptors for antigen produced through a somatic diversification process, and allowing for enhanced response to subsequent exposures to the same antigen (immunological memory).
cytokine production involved in immune response
The appearance of a cytokine due to biosynthesis or secretion following a cellular stimulus contributing to an immune response, resulting in an increase in its intracellular or extracellular levels.
An immune response taking place in the liver.
An immune system process that functions in the response of an organism to a tumor cell.
The process in which a relatively unspecialized hemopoietic precursor cell acquires the specialized features of a leukocyte. A leukocyte is an achromatic cell of the myeloid or lymphoid lineages capable of ameboid movement, found in blood or other tissue.
The synthesis or release of a cytokine following a inflammatory stimulus as part of an inflammatory response, resulting in an increase in its intracellular or extracellular levels.
cytokine production involved in inflammatory response
Process of any molecular function by which a gene product interacts selectively and non-covalently with DNA (deoxyribonucleic acid).
The chemical reactions and pathways resulting in the formation of ketones, a class of organic compounds that contain the carbonyl group, CO, and in which the carbonyl group is bonded only to carbon atoms. The general formula for a ketone is RCOR, where R and R are alkyl or aryl groups.
The selective, non-covalent, often stoichiometric, interaction of a molecule with one or more specific sites on another molecule.
In the definition of GO:0005488 binding is a subtype of Molecular function.
Interacting selectively and non-covalently with fatty acids, aliphatic monocarboxylic acids liberated from naturally occurring fats and oils by hydrolysis.
Interacting selectively and non-covalently with any protein or protein complex (a complex of two or more proteins that may include other nonprotein molecules).
Interacting selectively and non-covalently with phospholipids, a class of lipids containing phosphoric acid as a mono- or diester.
The part of a cell or its extracellular environment in which a gene product is located. A gene product may be located in one or more parts of a cell and its location may be as specific as a particular macromolecular complex, that is, a stable, persistent association of macromolecules that function together.
The space external to the outermost structure of a cell. For cells without external protective or external encapsulating structures this refers to space outside of the plasma membrane. This term covers the host cell environment outside an intracellular parasite.
Note that this term is intended to annotate gene products that are not attached to the cell surface. For gene products from multicellular organisms which are secreted from a cell but retained within the organism (i.e. released into the interstitial fluid or blood), consider the cellular component term 'extracellular space ; GO:0005615'.
That part of a multicellular organism outside the cells proper, usually taken to be outside the plasma membranes, and occupied by fluid.
Note that for multicellular organisms, the extracellular space refers to everything outside a cell, but still within the organism (excluding the extracellular matrix). Gene products from a multi-cellular organism that are secreted from a cell into the interstitial fluid or blood can therefore be annotated to this term.
The living contents of a cell; the matter contained within (but not including) the plasma membrane, usually taken to exclude large vacuoles and masses of secretory or ingested material. In eukaryotes it includes the nucleus and cytoplasm.
A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
A structure composed of a very long molecule of DNA and associated proteins (e.g. histones) that carries hereditary information.
Chromosomes include parts that are not part of the chromatin. Examples include the kinetochore.
All of the contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
A semiautonomous, self replicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration.
The outer, i.e. cytoplasm-facing, lipid bilayer of the mitochondrial envelope.
The inner, i.e. lumen-facing, lipid bilayer of the mitochondrial envelope. It is highly folded to form cristae.
A protein complex located in the mitochondrial inner membrane that forms part of the mitochondrial respiratory chain. It contains about 25 different polypeptide subunits, including NADH dehydrogenase (ubiquinone), flavin mononucleotide and several different iron-sulfur clusters containing non-heme iron. The iron undergoes oxidation-reduction between Fe(II) and Fe(III), and catalyzes proton translocation linked to the oxidation of NADH by ubiquinone.
mitochondrial respiratory chain complex I
A protein complex located in the mitochondrial inner membrane that forms part of the mitochondrial respiratory chain. Contains the 13 polypeptide subunits of cytochrome c oxidase, including cytochrome a and cytochrome a3. Catalyzes the oxidation of reduced cytochrome c by dioxygen (O2).
mitochondrial respiratory chain complex IV
A small lytic vacuole that has cell cycle-independent morphology and is found in most animal cells and that contains a variety of hydrolases, most of which have their maximal activities in the pH range 5-6. The contained enzymes display latency if properly isolated. About 40 different lysosomal hydrolases are known and lysosomes have a great variety of morphologies and functions.
Another function of the ER in eucaryotic cells is to sequester Ca2+ from the cytosol. Cell
Lysosome-endosome fusion and lysosome biogenesis. lysosomes can fuse directly with late endosomes to form a hybrid organelle. This has a led to a hypothesis that dense core lysosomes are in essence storage granules for acid hydrolases and that, when the former fuse with late endosomes, a hybrid organelle for digestion of endocytosed macromolecules is created. Lysosomes are then re-formed from hybrid organelles by a process involving condensation of contents.
The lipid bilayer surrounding the lysosome and separating its contents from the cell cytoplasm.
A vacuole to which materials ingested by endocytosis are delivered.
A membrane-bounded organelle that receives incoming material from primary endocytic vesicles that have been generated by clathrin-dependent and clathrin-independent endocytosis; vesicles fuse with the early endosome to deliver cargo for sorting into recycling or degradation pathways.
A prelysosomal endocytic organelle differentiated from early endosomes by lower lumenal pH and different protein composition. Late endosomes are more spherical than early endosomes and are mostly juxtanuclear, being concentrated near the microtubule organizing center.
A closed structure, found only in eukaryotic cells, that is completely surrounded by unit membrane and contains liquid material. Cells contain one or several vacuoles, that may have different functions from each other. Vacuoles have a diverse array of functions. They can act as a storage organelle for nutrients or waste products, as a degradative compartment, as a cost-effective way of increasing cell size, and as a homeostatic regulator controlling both turgor pressure and pH of the cytosol.
A double-membrane-bounded compartment that engulfs endogenous cellular material as well as invading microorganisms to target them to the vacuole/lysosome for degradation as part of macroautophagy.
A small organelle enclosed by a single membrane, and found in most eukaryotic cells. Contains peroxidases and other enzymes involved in a variety of metabolic processes including free radical detoxification, lipid catabolism and biosynthesis, and hydrogen peroxide metabolism.
The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached).
The ER has a central role in lipid and protein biosynthesis. Its membrane is the site of production of all the transmembrane proteins and lipids for most of the cell's organelles, including the ER itself, the Golgi apparatus, lysosomes, endosomes, secretory vesicles, and the plasma membrane. Another function of the ER in eucaryotic cells is to sequester Ca2+ from the cytosol.
The volume enclosed by the membranes of the endoplasmic reticulum.
The lipid bilayer surrounding the endoplasmic reticulum.
The smooth endoplasmic reticulum (smooth ER or SER) has no ribosomes attached to it. The smooth ER is the recipient of the proteins synthesized in the rough ER. Those proteins to be exported are passed to the Golgi complex, the resident proteins are returned to the rough ER and the lysosomal proteins after phosphorylation of their mannose residues are passed to the lysosomes. Glycosylation of the glycoproteins also continues. The smooth ER is the site of synthesis of lipids, including the phospholipids. The membranes of the smooth ER also contain enzymes that catalyze a series of reactions to detoxify both lipid-soluble drugs and harmful products of metabolism. Large quantities of certain compounds such as phenobarbital cause an increase in the amount of the smooth ER.
The hepatocyte is a cell with an abundant smooth ER.
It is usually prominent in cells that specialize in lipid metabolism. Cells that synthesize steroid hormones from cholesterol, for example, have an expanded smooth ER compartment to accommodate the enzymes needed to make cholesterol and to modify it to form the hormones. It is the principal site of production of lipoprotein particles, which carry lipids via the bloodstream to other parts of the body. The enzymes that synthesize the lipid components of lipoproteins are located in the membrane of the smooth ER, which also contains enzymes that catalyze a series of reactions to detoxify both lipid-soluble drugs and various harmful compounds produced by metabolism.
The rough (or granular) endoplasmic reticulum (ER) has ribosomes adhering to the outer surface; the ribosomes are the site of translation of the mRNA for those proteins which are either to be retained within the cisternae (ER-resident proteins), the proteins of the lysosomes, or the proteins destined for export from the cell. Glycoproteins undergo their initial glycosylation within the cisternae.
A compound membranous cytoplasmic organelle of eukaryotic cells, consisting of flattened, ribosome-free vesicles arranged in a more or less regular stack. The Golgi apparatus differs from the endoplasmic reticulum in often having slightly thicker membranes, appearing in sections as a characteristic shallow semicircle so that the convex side (cis or entry face) abuts the endoplasmic reticulum, secretory vesicles emerging from the concave side (trans or exit face). In vertebrate cells there is usually one such organelle, while in invertebrates and plants, where they are known usually as dictyosomes, there may be several scattered in the cytoplasm. The Golgi apparatus processes proteins produced on the ribosomes of the rough endoplasmic reticulum; such processing includes modification of the core oligosaccharides of glycoproteins, and the sorting and packaging of proteins for transport to a variety of cellular locations. Three different regions of the Golgi are now recognized both in terms of structure and function: cis, in the vicinity of the cis face, trans, in the vicinity of the trans face, and medial, lying between the cis and trans regions.
Note that the Golgi apparatus can be located in various places in the cytoplasm. In plants and lower animal cells, the Golgi apparatus exists as many copies of discrete stacks dispersed throughout the cytoplasm, while the Golgi apparatus of interphase mammalian cells is a juxtanuclear, often pericentriolar reticulum, where the discrete Golgi stacks are stitched together to form a compact and interconnected ribbon, sometimes called the Golgi ribbon.
The volume enclosed by the membranes of any cisterna or subcompartment of the Golgi apparatus, including the cis- and trans-Golgi networks.
An intracellular structure that can catalyze gamma-tubulin-dependent microtubule nucleation and that can anchor microtubules by interacting with their minus ends, plus ends or sides.
The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
An intracellular organelle, about 200 A in diameter, consisting of RNA and protein. It is the site of protein biosynthesis resulting from translation of messenger RNA (mRNA). It consists of two subunits, one large and one small, each containing only protein and RNA. Both the ribosome and its subunits are characterized by their sedimentation coefficients, expressed in Svedberg units (symbol: S). Hence, the prokaryotic ribosome (70S) comprises a large (50S) subunit and a small (30S) subunit, while the eukaryotic ribosome (80S) comprises a large (60S) subunit and a small (40S) subunit. Two sites on the ribosomal large subunit are involved in translation, namely the aminoacyl site (A site) and peptidyl site (P site). Ribosomes from prokaryotes, eukaryotes, mitochondria, and chloroplasts have characteristically distinct ribosomal proteins.
Any of the various filamentous elements that form the internal framework of cells, and typically remain after treatment of the cells with mild detergent to remove membrane constituents and soluble components of the cytoplasm. The term embraces intermediate filaments, microfilaments, microtubules, the microtrabecular lattice, and other structures characterized by a polymeric filamentous nature and long-range order within the cell. The various elements of the cytoskeleton not only serve in the maintenance of cellular shape but also have roles in other cellular functions, including cellular movement, cell division, endocytosis, and movement of organelles.
The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins
The chemical reactions and pathways involving carbohydrates, any of a group of organic compounds based of the general formula Cx(H2O)y. Includes the formation of carbohydrate derivatives by the addition of a carbohydrate residue to another molecule.
The chemical reactions and pathways involving glycogen, a polydisperse, highly branched glucan composed of chains of D-glucose residues in alpha-(1->4) glycosidic linkage, joined together by alpha-(1->6) glycosidic linkages.
The chemical reactions and pathways resulting in the formation of glycogen, a polydisperse, highly branched glucan composed of chains of D-glucose residues.
The chemical reactions and pathways resulting in the breakdown of glycogen, a polydisperse, highly branched glucan composed of chains of D-glucose residues.
Glycogen breakdown (glycogenolysis), Homo sapiens
The chemical reactions and pathways involving alcohols, any of a class of compounds containing one or more hydroxyl groups attached to a saturated carbon atom.
The chemical reactions and pathways resulting in the formation of precursor metabolites, substances from which energy is derived, and any process involved in the liberation of energy from these substances.
generation of precursor metabolites and energy
The formation of glucose from noncarbohydrate precursors, such as pyruvate, amino acids and glycerol.
The chemical reactions and pathways resulting in the breakdown of a carbohydrate into pyruvate, with the concomitant production of a small amount of ATP and the reduction of NAD(P) to NAD(P)H. Glycolysis begins with the metabolism of a carbohydrate to generate products that can enter the pathway and ends with the production of pyruvate. Pyruvate may be converted to acetyl-coenzyme A, ethanol, lactate, or other small molecules.
A nearly universal metabolic pathway in which the acetyl group of acetyl coenzyme A is effectively oxidized to two CO2 and four pairs of electrons are transferred to coenzymes. The acetyl group combines with oxaloacetate to form citrate, which undergoes successive transformations to isocitrate, 2-oxoglutarate, succinyl-CoA, succinate, fumarate, malate, and oxaloacetate again, thus completing the cycle. In eukaryotes the tricarboxylic acid is confined to the mitochondria.
Any process that modulates the frequency, rate or extent of the chemical reactions and pathways involving carbohydrates.
regulation of carbohydrate metabolic process
The phosphorylation of ADP to ATP that accompanies the oxidation of a metabolite through the operation of the respiratory chain. Oxidation of compounds establishes a proton gradient across the membrane, providing the energy for ATP synthesis.
The transfer of electrons from NADH to ubiquinone that occurs during oxidative phosphorylation, mediated by the multisubunit enzyme known as complex I.
oxidative phosphorylation, NADH to ubiquinone
mitochondrial electron transport, NADH to ubiquinone
The transfer of electrons from succinate to ubiquinone that occurs during oxidative phosphorylation, mediated by the multisubunit enzyme known as complex II.
mitochondrial electron transport, succinate to coenzyme Q
oxidative phosphorylation, succinate to ubiquinone
mitochondrial electron transport, succinate to ubiquinone
The transfer of electrons from ubiquinol to cytochrome c that occurs during oxidative phosphorylation, mediated by the multisubunit enzyme known as complex III.
complex III (ubiquinone to cytochrome c)
mitochondrial electron transport, ubiquinol to cytochrome c
The cellular metabolic process in which a cell duplicates one or more molecules of DNA. DNA replication begins when specific sequences, known as origins of replication, are recognized and bound by initiation proteins, and ends when the original DNA molecule has been completely duplicated and the copies topologically separated. The unit of replication usually corresponds to the genome of the cell, an organelle, or a virus. The template for replication can either be an existing DNA molecule or RNA.
The process of restoring DNA after damage. Genomes are subject to damage by chemical and physical agents in the environment (e.g. UV and ionizing radiations, chemical mutagens, fungal and bacterial toxins, etc.) and by free radicals or alkylating agents endogenously generated in metabolism. DNA is also damaged because of errors during its replication. A variety of different DNA repair pathways have been reported that include direct reversal, base excision repair, nucleotide excision repair, photoreactivation, bypass, double-strand break repair pathway, and mismatch repair pathway.
The addition of alkyl groups to many positions on all four bases of DNA. Alkylating agents can also modify the bases of incoming nucleotides in the course of DNA synthesis.
The covalent transfer of a methyl group to either N-6 of adenine or C-5 or N-4 of cytosine.
The cellular DNA metabolic process resulting in the breakdown of DNA, deoxyribonucleic acid, one of the two main types of nucleic acid, consisting of a long unbranched macromolecule formed from one or two strands of linked deoxyribonucleotides, the 3'-phosphate group of each constituent deoxyribonucleotide being joined in 3',5'-phosphodiester linkage to the 5'-hydroxyl group of the deoxyribose moiety of the next one.
The cleavage of DNA during apoptosis, which usually occurs in two stages: cleavage into fragments of about 50 kbp followed by cleavage between nucleosomes to yield 200 bp fragments.
DNA fragmentation in response to apoptotic signals is achieved through the activity of apoptotic nucleases. In human, these include DNA fragmentation factor (DFF) or caspase-activated DNase (CAD) and endonuclease G (Endo G) (reviewed in PMID:15723341). Caution is needed when apoptotic DNA laddering assays show presence of fragmented DNA. A positive assay may simply reflect the end point of a whole apoptotic process. Unless clear experimental evidence is available to show that a gene product is directly involved in fragmenting DNA, please do not annotate to GO:0006309 'apoptotic DNA fragmentation' and consider annotating instead to a more upstream process such as, e.g., GO:0042981 'regulation of apoptotic process', GO:0006915 'apoptotic process', GO:0097190 'apoptotic signaling pathway'. Also, note that gene products involved in compartmentalization of apoptotic nucleases and in activation or repression of their enzymatic activity should be annotated to the regulation term GO:1902510 'regulation of apoptotic DNA fragmentation' or to one of its children (see PMID:15723341).
Dynamic structural changes to eukaryotic chromatin occurring throughout the cell division cycle. These changes range from the local changes necessary for transcriptional regulation to global changes necessary for chromosome segregation.
The cellular synthesis of RNA on a template of DNA.
Any process that modulates the frequency, rate or extent of cellular DNA-templated transcription.
regulation of cellular transcription, DNA-dependent
regulation of transcription, DNA-templated
Any process in which a pre-mRNA or mRNA molecule is cleaved at specific sites or in a regulated manner.
The chemical reactions and pathways resulting in the breakdown of mRNA, messenger RNA, which is responsible for carrying the coded genetic 'message', transcribed from DNA, to sites of protein assembly at the ribosomes.
The cellular metabolic process in which a protein is formed, using the sequence of a mature mRNA or circRNA molecule to specify the sequence of amino acids in a polypeptide chain. Translation is mediated by the ribosome, and begins with the formation of a ternary complex between aminoacylated initiator methionine tRNA, GTP, and initiation factor 2, which subsequently associates with the small subunit of the ribosome and an mRNA or circRNA. Translation ends with the release of a polypeptide chain from the ribosome.
Any process that modulates the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of proteins by the translation of mRNA or circRNA.
The process of assisting in the covalent and noncovalent assembly of single chain polypeptides or multisubunit complexes into the correct tertiary structure.
Due to the crowded envirnoment within the cell, many proteins must interact with molecular chaperones to attain their native conformation (reviewed in Young et al., 2004). Chaperones recognize and associate with proteins in their non-native state and facilitate their folding by stabilizing the conformation of productive folding intermediates. Chaperones that take part broadly in de novo protein folding, such as the Hsp70s and the chaperonins, facilitate the folding process through cycles of substrate binding and release regulated by their ATPase activity (see Young et al., 2004; Spiess et al., 2004; Bigotti and Clarke, 2008).
The aggregation, arrangement and bonding together of a set of components to form a protein complex.
The addition of an acetyl group to a protein amino acid. An acetyl group is CH3CO-, derived from acetic [ethanoic] acid.
The removal of an acetyl group from a protein amino acid. An acetyl group is CH3CO-, derived from acetic [ethanoic] acid.
A protein modification process that results in the addition of a carbohydrate or carbohydrate derivative unit to a protein amino acid, e.g. the addition of glycan chains to proteins.
The covalent attachment of lipid groups to an amino acid in a protein.
The hydrolysis of proteins into smaller polypeptides and/or amino acids by cleavage of their peptide bonds.
This term was intentionally placed under 'protein metabolic process ; GO:0019538' rather than 'protein catabolic process ; GO:0030163' to cover all processes centered on breaking peptide bonds, including those involved in protein processing.
The removal of sugar residues from a glycosylated protein.
The chemical reactions and pathways involving amino acids, carboxylic acids containing one or more amino groups, as carried out by individual cells.
cellular amino acid and derivative metabolic process
The chemical reactions and pathways involving methionine (2-amino-4-(methylthio)butanoic acid), a sulfur-containing, essential amino acid found in peptide linkage in proteins.
The chemical reactions and pathways resulting in the formation of S-adenosylmethionine, S-(5'-adenosyl)-L-methionine, an important intermediate in one-carbon metabolism.
S-adenosylmethionine biosynthetic process
The chemical reactions and pathways involving lipids, compounds soluble in an organic solvent but not, or sparingly, in an aqueous solvent. Includes fatty acids; neutral fats, other fatty-acid esters, and soaps; long-chain (fatty) alcohols and waxes; sphingoids and other long-chain bases; glycolipids, phospholipids and sphingolipids; and carotenes, polyprenols, sterols, terpenes and other isoprenoids.
The chemical reactions and pathways involving fatty acids, aliphatic monocarboxylic acids liberated from naturally occurring fats and oils by hydrolysis.
The chemical reactions and pathways resulting in the formation of a fatty acid, any of the aliphatic monocarboxylic acids that can be liberated by hydrolysis from naturally occurring fats and oils. Fatty acids are predominantly straight-chain acids of 4 to 24 carbon atoms, which may be saturated or unsaturated; branched fatty acids and hydroxy fatty acids also occur, and very long chain acids of over 30 carbons are found in waxes.
A fatty acid oxidation process that results in the complete oxidation of a long-chain fatty acid. Fatty acid beta-oxidation begins with the addition of coenzyme A to a fatty acid, and occurs by successive cycles of reactions during each of which the fatty acid is shortened by a two-carbon fragment removed as acetyl coenzyme A; the cycle continues until only two or three carbons remain (as acetyl-CoA or propionyl-CoA respectively).
The chemical reactions and pathways involving phospholipids, any lipid containing phosphoric acid as a mono- or diester.
The chemical reactions and pathways resulting in the formation of phosphatidylethanolamine, any of a class of glycerophospholipids in which a phosphatidyl group is esterified to the hydroxyl group of ethanolamine.
phosphatidylethanolamine biosynthetic process
The transfer of a phospholipid from its site of synthesis to the plasma membrane.
The chemical reactions and pathways involving glycerophospholipids, any derivative of glycerophosphate that contains at least one O-acyl, O-alkyl, or O-alkenyl group attached to the glycerol residue.
The chemical reactions and pathways resulting in the formation of phosphatidic acid, any derivative of glycerol phosphate in which both the remaining hydroxyl groups of the glycerol moiety are esterified with fatty acids.
The chemical reactions and pathways resulting in the formation of phosphatidylglycerols, any of a class of phospholipids in which the phosphatidyl group is esterified to the hydroxyl group of glycerol.
phosphatidylglycerol biosynthetic process
The chemical reactions and pathways resulting in the formation of phosphatidylcholines, any of a class of glycerophospholipids in which the phosphatidyl group is esterified to the hydroxyl group of choline.
phosphatidylcholine biosynthetic process
The chemical reactions and pathways involving phosphatidylserines, any of a class of glycerophospholipids in which the phosphatidyl group is esterified to the hydroxyl group of L-serine. They are important constituents of cell membranes.
The chemical reactions and pathways resulting in the formation of phosphatidylserines, any of a class of glycerophospholipids in which the phosphatidyl group is esterified to the hydroxyl group of L-serine.
The chemical reactions and pathways resulting in the breakdown of phosphatidylserines, any of a class of glycerophospholipids in which the phosphatidyl group is esterified to the hydroxyl group of L-serine.
The chemical reactions and pathways resulting in the formation of phosphatidylinositol, any glycophospholipid in which the sn-glycerol 3-phosphate residue is esterified to the 1-hydroxyl group of 1D-myo-inositol.
Phosphatidylinositol (PI) is synthesized when phosphatidic acid (PA) and cytidine triphosphate (CTP) are converted into cytidine diphosphate-diacylglycerol (CDP-DAG) followed by conversion into PI and cytidine monophosphate (CMP) (Stuhne-Sekalec et al 1986, Lykidis et al. 1997).
phosphatidylinositol biosynthetic process
The chemical reactions and pathways involving sphingolipids, any of a class of lipids containing the long-chain amine diol sphingosine or a closely related base (a sphingoid).
The chemical reactions and pathways involving sphingomyelin, N-acyl-4-sphingenyl-1-O-phosphorylcholine, any of a class of phospholipids in which the amino group of sphingosine is in amide linkage with one of several fatty acids, while the terminal hydroxyl group of sphingosine is esterified to phosphorylcholine.
The chemical reactions and pathways resulting in the breakdown of sphingomyelin, N-acyl-4-sphingenyl-1-O-phosphorylcholine.
The chemical reactions and pathways resulting in the formation of sphingomyelin, N-acyl-4-sphingenyl-1-O-phosphorylcholine.
The chemical reaction resulting in the formation of cholesterol, cholest-5-en-3 beta-ol, the principal sterol of vertebrates and the precursor of many steroids, including bile acids and steroid hormones.
The chemical reactions resulting in the formation of bile acids, any of a group of steroid carboxylic acids occurring in bile.
The chemical reactions and pathways resulting in the breakdown of estrogens, C18 steroid hormones that can stimulate the development of female sexual characteristics. Also found in plants
A metabolic process that generates a pool of NADH by the reduction of NAD+.
reduced nicotinamide adenine dinucleotide regeneration
A metabolic process that generates a pool of NADPH by the reduction of NADP+.
reduced nicotinamide adenine dinucleotide phosphate regeneration
The chemical reactions and pathways involving glutathione, the tripeptide glutamylcysteinylglycine, which acts as a coenzyme for some enzymes and as an antioxidant in the protection of sulfhydryl groups in enzymes and other proteins; it has a specific role in the reduction of hydrogen peroxide (H2O2) and oxidized ascorbate, and it participates in the gamma-glutamyl cycle
The chemical reactions and pathways resulting in the formation of glutathione, the tripeptide glutamylcysteinylglycine, which acts as a coenzyme for some enzymes and as an antioxidant in the protection of sulfhydryl groups in enzymes and other proteins.
The chemical reaction resulting in the formation of ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
The chemical reactions and pathways resulting in the formation of heme, any compound of iron complexed in a porphyrin (tetrapyrrole) ring, from less complex precursors.
The chemical reactions and pathways involving the nonmetallic element phosphorus or compounds that contain phosphorus, usually in the form of a phosphate group (PO4).
The chemical reactions and physical changes involving a xenobiotic compound, a compound foreign to living organisms. Used of chemical compounds, e. g. a xenobiotic chemical, such as a pesticide. (Gene Ontology)
Xenobiotic biotransformation is metabolic conversion of xenobiotic chemicals to more hydrophilic (water-soluble) compounds.
Biotransfomation to harmful products is called toxication/metabolic activation [casarett and doull's toxicology 8th ed.]
The directed movement of substances (such as macromolecules, small molecules, ions) or cellular components (such as complexes and organelles) into, out of or within a cell, or between cells, or within a multicellular organism by means of some agent such as a transporter, pore or motor protein.
The directed movement of charged atoms or small charged molecules into, out of, within or between cells.
The directed movement of potassium ions (K+) into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
The directed movement of a neurotransmitter into, out of, within or between cells. Neurotransmitters are any chemical substance that is capable of transmitting (or inhibiting the transmission of) a nerve impulse from a neuron to another cell.
The directed movement of lipids into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. Lipids are compounds soluble in an organic solvent but not, or sparingly, in an aqueous solvent.
A vesicle-mediated transport process in which cells take up external materials or membrane constituents by the invagination of a small region of the plasma membrane to form a new membrane-bounded vesicle.
A vesicle-mediated transport process that results in the engulfment of external particulate material by phagocytes and their delivery to the lysosome. The particles are initially contained within phagocytic vacuoles (phagosomes), which then fuse with primary lysosomes to effect digestion of the particles.
The initial step in phagocytosis involving adhesion to bacteria, immune complexes and other particulate matter, or an apoptotic cell and based on recognition of factors such as bacterial cell wall components, opsonins like complement and antibody or protein receptors and lipids like phosphatidyl serine, and leading to intracellular signaling in the phagocytosing cell.
recognition of phagocytosed substance by phagocytic cell
Note that cell surface molecules involved in the direct binding of bacteria may be also annotated to the molecular function term 'bacterial cell surface binding ; GO:0051635'. Note that cell surface molecules involved in the direct binding to opsonins such as complement components or antibodies may be also annotated to the term 'opsonin binding ; GO:0001846'.
The directed movement of molecules between the nucleus and the cytoplasm.
The cellular catabolic process in which cells digest parts of their own cytoplasm; allows for both recycling of macromolecular constituents under conditions of cellular stress and remodeling the intracellular structure for cell differentiation
A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died.
Any process involved in the controlled self-propelled movement of a cell that results in translocation of the cell from one place to another.
Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a disturbance in organismal or cellular homeostasis, usually, but not necessarily, exogenous (e.g. temperature, humidity, ionizing radiation).
Any immune system process that functions in the calibrated response of an organism to a potential internal or invasive threat.
cellular response to DNA damage stimulus
Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating damage to its DNA from environmental insults or errors during metabolism.
Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of oxidative stress, a state often resulting from exposure to high levels of reactive oxygen species, e.g. superoxide anions, hydrogen peroxide (H2O2), and hydroxyl radicals.
A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of an organelle within a cell. An organelle is an organized structure of distinctive morphology and function. Includes the nucleus, mitochondria, plastids, vacuoles, vesicles, ribosomes and the cytoskeleton.
A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a mitochondrion; includes mitochondrial morphogenesis and distribution, and replication of the mitochondrial genome as well as synthesis of new mitochondrial components.
A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures.
A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments. Includes processes that control the spatial distribution of actin filaments, such as organizing filaments into meshworks, bundles, or other structures, as by cross-linking.
A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of the cytoplasm. The cytoplasm is all of the contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a vacuole.
The directed movement of substances into, out of or within a lysosome.
The progression of biochemical and morphological phases and events that occur in a cell during successive cell replication or nuclear replication events. Canonically, the cell cycle comprises the replication and segregation of genetic material followed by the division of the cell, but in endocycles or syncytial cells nuclear replication or nuclear division may not be followed by cell division.
A regulatory process that halts progression through the cell cycle during one of the normal phases (G1, S, G2, M).
The attachment of a cell, either to another cell or to the extracellular matrix, via cell adhesion molecules.
A series of molecular signals initiated by binding of a ligand to the tyrosine kinase receptor EGFR (ERBB1) on the surface of a cell. The pathway ends with regulation of a downstream cellular process, e.g. transcription.
epidermal growth factor receptor signaling pathway
A series of molecular signals initiated by the binding of an extracellular ligand to a transforming growth factor beta receptor on the surface of a target cell, and ending with regulation of a downstream cellular process, e.g. transcription.
transforming growth factor beta receptor signaling pathway
A series of molecular signals initiated by the binding of an extracellular ligand to the receptor Notch on the surface of a target cell, and ending with regulation of a downstream cellular process, e.g. transcription.
The process in which a signal is passed on to downstream components within the cell through the I-kappaB-kinase (IKK)-dependent activation of NF-kappaB. The cascade begins with activation of a trimeric IKK complex (consisting of catalytic kinase subunits IKKalpha and/or IKKbeta, and the regulatory scaffold protein NEMO) and ends with the regulation of transcription of target genes by NF-kappaB. In a resting state, NF-kappaB dimers are bound to I-kappaB proteins, sequestering NF-kappaB in the cytoplasm. Phosphorylation of I-kappaB targets I-kappaB for ubiquitination and proteasomal degradation, thus releasing the NF-kappaB dimers, which can translocate to the nucleus to bind DNA and regulate transcription. PMID:12773372
I-kappaB kinase-NF-kappaB signal transduction pathway
The selective interaction of the transcription factor NF-kappaB with specific molecules in the cytoplasm, thereby inhibiting its translocation into the nucleus.
Behavior associated with the intake of food.
The chemical reactions and pathways, including anabolism and catabolism, by which living organisms transform chemical substances. Metabolic processes typically transform small molecules, but also include macromolecular processes such as DNA repair and replication, and protein synthesis and degradation.
Note that metabolic processes do not include single functions or processes such as protein-protein interactions, protein-nucleic acids, nor receptor-ligand interactions.
The chemical reactions and pathways involving estrogens, C18 steroid hormones that can stimulate the development of female sexual characteristics. Also found in plants.
Any biological process that results in permanent cessation of all vital functions of a cell. A cell should be considered dead when any one of the following molecular or morphological criteria is met: (1) the cell has lost the integrity of its plasma membrane; (2) the cell, including its nucleus, has undergone complete fragmentation into discrete bodies (frequently referred to as apoptotic bodies). The cell corpse (or its fragments) may be engulfed by an adjacent cell in vivo, but engulfment of whole cells should not be considered a strict criteria to define cell death as, under some circumstances, live engulfed cells can be released from phagosomes (see PMID:18045538).
The multiplication or reproduction of cells, resulting in the rapid expansion of a cell population.
This term was moved out from being a child of 'cellular process' because it is a cell population-level process, and cellular processes are restricted to those processes that involve individual cells. Also note that this term is intended to be used for the proliferation of cells within a multicellular organism, not for the expansion of a population of single-celled organisms.
The series of molecular signals generated as a consequence of the insulin receptor binding to insulin.
Interacting selectively and non-covalently with a lipid.
The process of removing sections of the primary RNA transcript to remove sequences not present in the mature form of the RNA and joining the remaining sections to form the mature form of the RNA.
Interacting selectively and non-covalently with phosphatidylethanolamine, any of a class of glycerophospholipids in which a phosphatidyl group is esterified to the hydroxyl group of ethanolamine.
The chemical reactions and pathways resulting in the formation of lipids, compounds soluble in an organic solvent but not, or sparingly, in an aqueous solvent.
A series of molecular signals in which a signal is conveyed from the cell surface to trigger the apoptotic death of a cell. The pathway starts with a ligand binding to a death domain receptor on the cell surface, and ends when the execution phase of apoptosis is triggered.
extrinsic apoptotic signaling pathway via death domain receptors
Gene products that may be annotated to this term include: 1) ligands such as FASL; 2) receptors such as FAS/CD95 (though care should be taken because FAS can also act as a non-apoptotic signal transducer); 3) signaling molecules such as FADD (FAS-associated protein with a death domain), cIAPs (cellular inhibitor of apoptosis proteins), c-FLIPs and caspases 8 and 10. Examples are TWEAK (TNF12) and FN14 (TNFRSF12A) (UniProt symbols O43508 and Q9NP84)
The directed movement of carbohydrate into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. Carbohydrates are any of a group of organic compounds based of the general formula Cx(H2O)y.
The chemical reactions and pathways resulting in the formation of phospholipids, any lipid containing phosphoric acid as a mono- or diester.
The chemical reactions and pathways resulting in the breakdown of substances, including the breakdown of carbon compounds with the liberation of energy for use by the cell or organism.
The chemical reactions and pathways resulting in the formation of substances; typically the energy-requiring part of metabolism in which simpler substances are transformed into more complex ones.
The chemical reactions and pathways resulting in the breakdown of a fatty acid, any of the aliphatic monocarboxylic acids that can be liberated by hydrolysis from naturally occurring fats and oils. Fatty acids are predominantly straight-chain acids of 4 to 24 carbon atoms, which may be saturated or unsaturated; branched fatty acids and hydroxy fatty acids also occur, and very long chain acids of over 30 carbons are found in waxes.
The chemical reactions and pathways resulting in the formation of cobalamin (vitamin B12), a water-soluble vitamin characterized by possession of a corrin nucleus containing a cobalt atom.
The chemical reactions and pathways resulting in the formation of glycolipid, a class of 1,2-di-O-acylglycerols joined at oxygen 3 by a glycosidic linkage to a carbohydrate part (usually a mono-, di- or tri-saccharide).
Translational attenuation is a regulatory mechanism analogous to ribosome-mediated transcriptional attenuation. the system requires the presence of a short orf, called a leader peptide, encoded in the mrna upstream of the ribosome-binding site and start codon of the gene whose translation is to be regulated. certain conditions, such as presence of the antibiotic tetracycline in bacteria or amino acid starvation, may cause slowing or stalling of the ribosome translating the leader peptide. the stalled ribosome masks a region of the mrna and affects which of two alternative mrna folded structures will form, therefore controlling whether or not a ribosome will bind and initiate translation of the downstream gene. translational attenuation is analogous to ribosome-mediated transcriptional attenuation, in which mrna remodeling caused by ribosome stalling regulates transcriptional termination rather than translational initiation.
The chemical reactions and pathways resulting in the breakdown of phospholipids, any lipid containing phosphoric acid as a mono- or diester.
The chemical reactions and pathways involving a toxin, a poisonous compound (typically a protein) that is produced by cells or organisms and that can cause disease when introduced into the body or tissues of an organism.
Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an external stimulus.
Note that this term is in the subset of terms that should not be used for direct gene product annotation. Instead, select a child term or, if no appropriate child term exists, please request a new term. Direct annotations to this term may be amended during annotation QC.
Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus arising within the organism.
The process in which a gene's sequence is converted into a mature gene product or products (proteins or RNA). This includes the production of an RNA transcript as well as any processing to produce a mature RNA product or an mRNA or circRNA (for protein-coding genes) and the translation of that mRNA or circRNA into protein. Protein maturation is included when required to form an active form of a product from an inactive precursor form.
A changing process to convert a gene's sequenes into a mature gene prduct(s), i.e., (m)RNA, or protein.
Any process that modulates the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product or products (proteins or RNA). This includes the production of an RNA transcript as well as any processing to produce a mature RNA product or an mRNA or circRNA (for protein-coding genes) and the translation of that mRNA or circRNA into protein. Protein maturation is included when required to form an active form of a product from an inactive precursor form.
This class covers any process that regulates the rate of production of a mature gene product, and so includes processes that regulate that rate by regulating the level, stability or availability of intermediates in the process of gene expression. For example, it covers any process that regulates the level, stability or availability of mRNA or circRNA for translation and thereby regulates the rate of production of the encoded protein via translation.
The chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds that is mediated by the proteasome.
proteasome-mediated protein catabolic process
Any process that modulates the frequency, rate or extent of autophagy. Autophagy is the process in which cells digest parts of their own cytoplasm.
Any process that stops, prevents, or reduces the frequency, rate or extent of autophagy. Autophagy is the process in which cells digest parts of their own cytoplasm.
Any process that activates, maintains or increases the rate of autophagy. Autophagy is the process in which cells digest parts of their own cytoplasm.
Any process that increases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product or products (proteins or RNA). This includes the production of an RNA transcript as well as any processing to produce a mature RNA product or an mRNA or circRNA (for protein-coding genes) and the translation of that mRNA or circRNA into protein. Protein maturation is included when required to form an active form of a product from an inactive precursor form.
Any process that decreases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product or products (proteins or RNA). This includes the production of an RNA transcript as well as any processing to produce a mature RNA product or an mRNA or circRNA (for protein-coding genes) and the translation of that mRNA or circRNA into protein. Protein maturation is included when required to form an active form of a product from an inactive precursor form.
This term covers any process that negatively regulates the rate of production of a mature gene product, and so includes processes that negatively regulate that rate by reducing the level, stability or availability of intermediates in the process of gene expression. For example, it covers any process that reduces the level, stability or availability of mRNA or circRNA for translation and thereby reduces the rate of production of the encoded protein via translation.
Any process that decreases the rate, frequency or extent of extracellular matrix disassembly. Extracellular matrix disassembly is a process that results in the breakdown of the extracellular matrix.
negative regulation of extracellular matrix disassembly
The process in which a monocyte acquires the specialized features of a foam cell. A foam cell is a type of cell containing lipids in small vacuoles and typically seen in atherosclerotic lesions, as well as other conditions.
macrophage derived foam cell differentiation
Any process that modulates the rate, frequency or extent of macrophage derived foam cell differentiation. Macrophage derived foam cell differentiation is the process in which a macrophage acquires the specialized features of a foam cell. A foam cell is a type of cell containing lipids in small vacuoles and typically seen in atherosclerotic lesions, as well as other conditions.
regulation of macrophage derived foam cell differentiation
Any process that increases the rate, frequency or extent of macrophage derived foam cell differentiation. Macrophage derived foam cell differentiation is the process in which a macrophage acquires the specialized features of a foam cell. A foam cell is a type of cell containing lipids in small vacuoles and typically seen in atherosclerotic lesions, as well as other conditions.
positive regulation of macrophage derived foam cell differentiation
Any process that decreases the rate, frequency or extent of macrophage derived foam cell differentiation. Macrophage derived foam cell differentiation is the process in which a macrophage acquires the specialized features of a foam cell. A foam cell is a type of cell containing lipids in small vacuoles and typically seen in atherosclerotic lesions, as well as other conditions.
negative regulation of macrophage derived foam cell differentiation
The accumulation and maintenance in cells or tissues of cholesterol, cholest-5-en-3 beta-ol, the principal sterol of vertebrates and the precursor of many steroids, including bile acids and steroid hormones.
Any process that decreases the rate, frequency or extent of lipid storage. Lipid storage is the accumulation and maintenance in cells or tissues of lipids, compounds soluble in organic solvents but insoluble or sparingly soluble in aqueous solvents. Lipid reserves can be accumulated during early developmental stages for mobilization and utilization at later stages of development.
Any process that decreases the rate, frequency or extent of phosphatidylcholine catabolism. Phosphatidylcholine catabolic processes are the chemical reactions and pathways resulting in the breakdown of phosphatidylcholines, any of a class of glycerophospholipids in which the phosphatidyl group is esterified to the hydroxyl group of choline.
negative regulation of phosphatidylcholine catabolic process
Any process that modulates the rate or frequency of cell death. Cell death is the specific activation or halting of processes within a cell so that its vital functions markedly cease, rather than simply deteriorating gradually over time, which culminates in cell death. [
The directed movement of bile acid and bile salts into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
Enables the transfer of bile acid from one side of a hepatocyte plasma membrane into a bile canaliculus. Bile canaliculi are the thin tubes formed by hepatocyte membranes. Bile acids are any of a group of steroid carboxylic acids occurring in bile, where they are present as the sodium salts of their amides with glycine or taurine.
The directed movement of choline into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. Choline (2-hydroxyethyltrimethylammonium) is an amino alcohol that occurs widely in living organisms as a constituent of certain types of phospholipids and in the neurotransmitter acetylcholine.
The directed movement of a drug, a substance used in the diagnosis, treatment or prevention of a disease, into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
The directed movement of fatty acids into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. Fatty acids are aliphatic monocarboxylic acids liberated from naturally occurring fats and oils by hydrolysis
The directed movement of long-chain fatty acids into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. A long-chain fatty acid is a fatty acid with a chain length between C13 and C22.
The directed movement of long-chain fatty acids into a peroxisome. A long-chain fatty acid is a fatty acid with a chain length between C13 and C22.
long-chain fatty acid import into peroxisome
The directed movement of phospholipids into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. Phospholipids are any lipids containing phosphoric acid as a mono- or diester.
The transport of protons against an electrochemical gradient, using energy from electron transport.
electron transport coupled proton transport
The chemical reactions and pathways resulting in the breakdown of lipids, compounds soluble in an organic solvent but not, or sparingly, in an aqueous solvent.
The process in which a cell irreversibly increases in size over time by accretion and biosynthetic production of matter similar to that already present.
The chemical reactions and pathways resulting in the formation of carbohydrates, any of a group of organic compounds based of the general formula Cx(H2O)y.
The chemical reactions and pathways resulting in the breakdown of carbohydrates, any of a group of organic compounds based of the general formula Cx(H2O)y.
catabolic carbohydrate metabolic process
A cellular transport process in which transported substances are moved in membrane-bounded vesicles; transported substances are enclosed in the vesicle lumen or located in the vesicle membrane. The process begins with a step that directs a substance to the forming vesicle, and includes vesicle budding and coating. Vesicles are then targeted to, and fuse with, an acceptor membrane.
The directed movement of substances mediated by an endosome, a membrane-bounded organelle that carries materials enclosed in the lumen or located in the endosomal membrane.
Assembly of gap junctions, which are found in most animal tissues, and serve as direct connections between the cytoplasms of adjacent cells. They provide open channels through the plasma membrane, allowing ions and small molecules (less than approximately a thousand daltons) to diffuse freely between neighboring cells, but preventing the passage of proteins and nucleic acids.
The process of introducing a phosphate group into a molecule, usually with the formation of a phosphoric ester, a phosphoric anhydride or a phosphoric amide.
The process of removing one or more phosphoric (ester or anhydride) residues from a molecule.
The controlled self-propelled movement of a cell from one site to a destination guided by molecular cues. Cell migration is a central process in the development and maintenance of multicellular organisms.
Any protein maturation process achieved by the cleavage of a peptide bond or bonds within a protein. Protein maturation is the process leading to the attainment of the full functional capacity of a protein.
protein maturation by peptide bond cleavage
The removal of one or more ubiquitin groups from a protein.
The process in which a SUMO protein (small ubiquitin-related modifier) is conjugated to a target protein via an isopeptide bond between the carboxyl terminus of SUMO with an epsilon-amino group of a lysine residue of the target protein.
Interacting selectively and non-covalently with any triester of glycerol.
The chemical reactions and pathways involving a drug, a substance used in the diagnosis, treatment or prevention of a disease; as used here antibiotic substances (see antibiotic metabolism) are considered to be drugs, even if not used in medical or veterinary practice.
The covalent attachment of a myristoyl group to a protein.
The modification of a protein by amino acid glucuronidation.
Any process that modulates the frequency, rate or extent of the chemical reactions and pathways involving lipids.
Any process that modulates the frequency, rate or extent of the chemical reactions and pathways within a cell or an organism.
The removal of one or more electrons from a fatty acid, with or without the concomitant removal of a proton or protons, by reaction with an electron-accepting substance, by addition of oxygen or by removal of hydrogen.
The chemical reactions and pathways involving a protein. Includes protein modification.
The chemical reactions and pathways involving glucuronate, any salt or ester of glucuronic acid, the uronic acid formally derived from glucose by oxidation of the hydroxymethylene group at C-6 to a carboxyl group.
The rupture of cell membranes and the loss of cytoplasm.
The accumulation and maintenance in cells or tissues of lipids, compounds soluble in organic solvents but insoluble or sparingly soluble in aqueous solvents. Lipid reserves can be accumulated during early developmental stages for mobilization and utilization at later stages of development.
One of the distinct periods or stages into which the cell cycle is divided. Each phase is characterized by the occurrence of specific biochemical and morphological events.
A process that results in the breakdown of the extracellular matrix.
The aggregation, arrangement and bonding together of a cellular component.
cellular component assembly at cellular level
A process in which a series of electron carriers operate together to transfer electrons from donors to any of several different terminal electron acceptors to generate a transmembrane electrochemical gradient.
A process in which a series of electron carriers operate together to transfer electrons from donors such as NADH and FADH2 to any of several different terminal electron acceptors to generate a transmembrane electrochemical gradient.
Any process that modulates the frequency, rate or extent of a signaling process.
The entirety of a process in which information is transmitted within a biological system. This process begins with an active signal and ends when a cellular response has been triggered.
Note that a signal is any variable property or parameter that serves to convey information, and may be a physical entity such as a gene product or small molecule, a photon, or a change in state such as movement or voltage change.
Any process that stops, prevents, or reduces the frequency, rate or extent of a signaling process.
Formation of a lamellipodium, a thin sheetlike extension of the surface of a migrating cell.
A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments and their associated proteins.
actin cytoskeleton organization and biogenesis
The regulated release of proinsulin from secretory granules accompanied by cleavage of proinsulin to form mature insulin. In vertebrates, insulin is secreted from B granules in the B cells of the vertebrate pancreas and from insulin-producing cells in insects.
The process of restoring a protein to its original state after damage by such things as oxidation or spontaneous decomposition of residues.
The process in which a relatively unspecialized precursor cell acquires specialized features of a lymphocyte. A lymphocyte is a leukocyte commonly found in the blood and lymph that has the characteristics of a large nucleus, a neutral staining cytoplasm, and prominent heterochromatin.
Note that immunologists typically use the word 'development' to refer to cells of B or T cell lineages undergoing the process that GO describes as 'cell differentiation'.
The change in morphology and behavior of a natural killer cell in response to a cytokine, chemokine, cellular ligand, or soluble factor.
The process in which relatively unspecialized cells, e.g. embryonic or regenerative cells, acquire specialized structural and/or functional features that characterize the cells, tissues, or organs of the mature organism or some other relatively stable phase of the organism's life history. Differentiation includes the processes involved in commitment of a cell to a specific fate and its subsequent development to the mature state.
The chemical reactions and pathways resulting in the breakdown of a protein by the destruction of the native, active configuration, with or without the hydrolysis of peptide bonds.
This term refers to the breakdown of mature proteins. For cleavage events involved in generating a mature protein from a precursor, consider instead the term 'protein maturation ; GO:0051604' and its children.
A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of structures in the space external to the outermost structure of a cell. For cells without external protective or external encapsulating structures this refers to space outside of the plasma membrane, and also covers the host cell environment outside an intracellular parasite.
The process in which a precursor cell type acquires characteristics of a more mature T-cell. A T cell is a type of lymphocyte whose definin characteristic is the expression of a T cell receptor complex.
The process in which a relatively unspecialized monocyte acquires the specialized features of a macrophage.
The process in which peroxisomes are delivered to the vacuole and degraded in response to changing nutrient conditions.
The directed movement of cholesterol, cholest-5-en-3-beta-ol, into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
Any process that stops, prevents, or reduces the frequency, rate or extent of any TGF-beta receptor signaling pathway.
negative regulation of transforming growth factor beta receptor signaling pathway
The movement of a leukocyte in response to an external stimulus.
The process of binding or confining any triester of glycerol such that it is separated from other components of a biological system.
The process in which a relatively unspecialized cell acquires specialized features of an epithelial cell, any of the cells making up an epithelium.
The post-translational removal of peptide sequences from within a protein sequence.
The series of molecular signals generated as a consequence of the presence of unfolded proteins in the endoplasmic reticulum (ER) or other ER-related stress; results in changes in the regulation of transcription and translation.
Note that this term should not be confused with 'response to unfolded protein ; GO:0006986', which refers to any response to the presence of unfolded proteins anywhere in the cell or in multicellular organism. Also see 'ER-associated protein catabolic process ; GO:0030433'.
endoplasmic reticulum unfolded protein response
The directed movement of unfolded or misfolded proteins from the endoplasmic reticulum to the cytosol through the translocon.
protein retrotranslocation, ER to cytosol
retrograde protein transport, endoplasmic reticulum to cytosol
retrograde protein transport, ER to cytosol
A structure lying external to one or more cells, which provides structural support for cells or tissues.
A membrane that is one of the two lipid bilayers of an organelle envelope or the outermost membrane of single membrane bound organelle.
A series of molecular signals in which a stress-activated protein kinase (SAPK) cascade relays one or more of the signals.
stress-activated protein kinase signaling cascade
An intracellular protein kinase cascade containing at least a JNK (a MAPK), a JNKK (a MAPKK) and a JUN3K (a MAP3K). The cascade can also contain two additional tiers: the upstream MAP4K and the downstream MAP Kinase-activated kinase (MAPKAPK). The kinases in each tier phosphorylate and activate the kinases in the downstream tier to transmit a signal within a cell.
The chemical reactions and pathways resulting in the breakdown of phosphatidylinositol, any glycophospholipid with its sn-glycerol 3-phosphate residue is esterified to the 1-hydroxyl group of 1D-myo-inositol.
Interacting selectively and non-covalently with phosphatidylcholine, a class of glycophospholipids in which a phosphatidyl group is esterified to the hydroxyl group of choline.
Any process that stops, prevents, or reduces the frequency, rate or extent of protein complex assembly.
down regulation of protein complex assembly
down-regulation of protein complex assembly
downregulation of protein complex assembly
negative regulation of protein complex assembly
A process that is carried out at the cellular level which results in dynamic structural changes to the arrangement of constituent parts of cytoskeletal structures comprising actin filaments and their associated proteins.
Any homeostatic process in which an organism produces heat, thereby raising its internal temperature.
A series of molecular signals mediated by TOR (Target of rapamycin) proteins, members of the phosphoinositide (PI) 3-kinase related kinase (PIKK) family that act as serine/threonine kinases in response to nutrient availability or growth factors.
Either of the lipid bilayers that surround the nucleus and form the nuclear envelope; excludes the intermembrane space.
Either of the lipid bilayers that surround the mitochondrion and form the mitochondrial envelope.
Any small, fluid-filled, spherical organelle enclosed by membrane.
The chemical reactions and pathways resulting in the breakdown of mitochondrial DNA.
The chemical reactions and pathways resulting in the formation of cardiolipin, 1,3-bis(3-phosphatidyl)glycerol.
diphosphatidylglycerol biosynthetic process
The assembly of a bleb, a cell extension caused by localized decoupling of the cytoskeleton from the plasma membrane and characterized by rapid formation, rounded shape, and scarcity of organelles within the protrusion. Plasma membrane blebbing occurs during apoptosis and other cellular processes, including cell locomotion, cell division, and as a result of physical or chemical stresses.
The process in which a methyl group is covalently attached to a molecule.
The directed movement of membrane-bounded vesicles from recycling endosomes back to the plasma membrane where they are recycled for further rounds of transport.
retrograde transport of endocytic vesicles
The appearance of a chemokine due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels.
The appearance of type I interferon due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels. Type I interferons include the interferon-alpha, beta, delta, episilon, zeta, kappa, tau, and omega gene families.
The appearance of interferon-gamma due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels. Interferon-gamma is also known as type II interferon.
The appearance of interleukin-1 beta due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels.
The appearance of interleukin-1 due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels.
The appearance of interleukin-2 due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels.
The appearance of tumor necrosis factor due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels.
The regulated release of bile acid, composed of any of a group of steroid carboxylic acids occurring in bile, by a cell or a tissue.
Bile contains bile acids, glutathione, phospholipids, cholesterol, bilirubin, and other organic anions, proteins, metals, ions, and xenobiotics. Hepatocytes begins the formation of bile by transporting bile acids, glutathione, and other solutes including Xenobiotics and their metabolites into the canalicular lumen. The major driving force of bile formation is the active transport of bile salts and other osmolytes into the canalicular lumen. Most conjugated bile acids (taurine and glycine conjugates) and some unconjugated bile acids are transported into hepatocytes by sodium-dependent transporters. Sodium-independent uptake of conjugated and unconjugated bile acids is performed by members of the organic anion-transporting polypeptides (OATPs). OATPs also transport numerous drugs and hepatotoxicants. Lipophilic cationic drugs, estrogens, and lipids are exported by the canalicular multiple-drug resistance (MDR) P-glycoproteins, one of which is exclusive for phospholipids. Conjugates of glutathione, glucuronide, and sulfate are exported by multidrug resistance-associated protein2 (MRP2).
transforming growth factor beta1 production
The appearance of transforming growth factor-beta1 due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels.
The aggregation, arrangement and bonding together of a set of components to form mitochondrial respiratory chain complex I.
mitochondrial NADH dehydrogenase complex (ubiquinone) assembly
mitochondrial respiratory chain complex I assembly
The aggregation, arrangement and bonding together of a set of components to form a mitochondrial respiratory chain complex.
mitochondrial respiratory chain complex assembly
A series of molecular signals initiated by the binding of a tumor necrosis factor to a receptor on the surface of a cell, and ending with regulation of a downstream cellular process, e.g. transcription.
tumor necrosis factor-mediated signaling pathway
The directed movement of cholesterol, cholest-5-en-3-beta-ol, out of a cell or organelle.
The aggregation, arrangement and bonding together of a set of components to form respiratory chain complex IV (also known as cytochrome c oxidase) in the mitochondrial inner membrane.
mitochondrial cytochrome c oxidase biogenesis
mitochondrial cytochrome c oxidase complex assembly
mitochondrial respiratory chain complex IV assembly
The directed movement of a phospholipid out of a cell or organelle.
Any series of molecular signals generated as a consequence of binding to toll-like receptor 4.
Any series of molecular signals generated as a consequence of binding to toll-like receptor 9.
The directed movement of triglyceride into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. Triglycerides are important components of plant oils, animal fats and animal plasma lipoproteins.
A cellular process that results in the aggregation, arrangement and bonding together of a set of components to form a cell junction.
The aggregation, arrangement and bonding together of a set of components to form an adherens junction. An adherens junction is a cell junction at which the cytoplasmic face of the plasma membrane is attached to actin filaments.
The non-covalent aggregation and arrangement of proteins and lipids in the liver to form a very-low-density lipoprotein particle.
very-low-density lipoprotein particle assembly
A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a lipid particle.
The removal of one or more electrons from a lipid, with or without the concomitant removal of a proton or protons, by reaction with an electron-accepting substance, by addition of oxygen or by removal of hydrogen.
The chemical reactions and pathways resulting in the breakdown of phosphatidylglycerols, any of a class of glycerophospholipids in which the phosphatidyl group is esterified to the hydroxyl group of glycerol.
The aggregation, arrangement and bonding together of a set of components to form the cytochrome bc(1) complex (also known as ubiquinol-cytochrome c reductase), in the mitochondrial inner membrane.
mitochondrial cytochrome bc(1) complex assembly
mitochondrial respiratory chain complex III assembly
The aggregation, arrangement and bonding together of a set of components to form respiratory chain complex II, in the mitochondrial inner membrane.
mitochondrial respiratory chain complex II assembly
The directed movement of glutathione, the tripeptide glutamylcysteinylglycine, into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
The chemical reactions and pathways resulting in the breakdown of phosphatidylcholines, any of a class of glycerophospholipids in which the phosphatidyl group is esterified to the hydroxyl group of choline.
Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stress acting at the endoplasmic reticulum. ER stress usually results from the accumulation of unfolded or misfolded proteins in the ER lumen.
cellular response to endoplasmic reticulum stress
response to endoplasmic reticulum stress
Downregulation of gene expression through the action of microRNAs (miRNAs), endogenous 21-24 nucleotide small RNAs processed from stem-loop RNA precursors (pre-miRNAs). Once incorporated into a RNA-induced silencing complex (RISC), miRNAs can downregulate gene expression by either of two posttranscriptional mechanisms: endolytic cleavage of mRNA cleavage or translational repression, usually accompanied by poly-A tail shortening and subsequent degradation of the mRNA.
Positive regulation of an adaptive immune response mediated via cytokine production by helper T cell.
helper T cell enhancement of adaptive immune response
The removal of an acyl group, any group or radical of the form RCO- where R is an organic group, from a protein amino acid.
A change in the morphology or behavior of a hepatic stellate cell resulting from exposure to a cytokine, chemokine, hormone, cellular ligand or soluble factor.
Any process that increases the frequency, rate or extent of the passage or uptake of molecules by the mitochondrial membrane.
positive regulation of mitochondrial membrane permeability
Interacting selectively and non-covalently with a long-chain fatty acid. A long-chain fatty acid is a fatty acid with a chain length between C13 and C22.
Interacting selectively and non-covalently with a long-chain fatty acyl-CoA. A long-chain fatty acyl-CoA is any derivative of coenzyme A in which the sulfhydryl group is in a thioester linkage with a long-chain fatty-acyl group. Long-chain fatty-acyl-CoAs have chain lengths of C13 or more.
The covalent alteration of one or more amino acids occurring in proteins, peptides and nascent polypeptides (co-translational, post-translational modifications). Includes the modification of charged tRNAs that are destined to occur in a protein (pre-translation modification).
A series of molecular signals initiated by the binding of a ligand to the receptor Fas on the surface of the cell, and ending with regulation of a downstream cellular process, e.g. transcription. Fas is a death domain-containing member of the tumor necrosis factor receptor (TNFR) superfamily.
A series of molecular signals mediated by the endoplasmic reticulum stress sensor IRE1 (Inositol-requiring transmembrane kinase/endonuclease). Begins with activation of IRE1 in response to endoplasmic reticulum (ER) stress, and ends with regulation of a downstream cellular process, e.g. transcription. One target of activated IRE1 is the transcription factor HAC1 in yeast, or XBP1 in mammals; IRE1 cleaves an intron of a mRNA coding for HAC1/XBP1 to generate an activated HAC1/XBP1 transcription factor, which controls the up regulation of UPR-related genes. At least in mammals, IRE1 can also signal through additional intracellular pathways including JNK and NF-kappaB.
endoplasmic reticulum unfolded protein response; IRE1 signaling
A series of molecular signals mediated by the endoplasmic reticulum membrane stress sensor PERK (PKR-like ER kinase). Begins with activation of PERK in response to endoplasmic reticulum (ER) stress and ends with regulation of a downstream cellular process, e.g. transcription. The main substrate of PERK is the translation initiation factor eIF2alpha. Serine-phosphorylation of eIF2alpha by PERK inactivates eIF2alpha and inhibits general protein translation. In addition, eIF2alpha phosphorylation preferentially increases the translation of selective mRNAs such as ATF4 (activating transcription factor 4), which up regulates a subset of UPR genes required to restore folding capacity.
endoplasmic reticulum unfolded protein response; PERK signaling
A series of molecular signals mediated by the endoplasmic reticulum membrane stress sensor ATF6 (activating transcription factor 6). Begins with activation of ATF6 in response to endoplasmic reticulum (ER) stress, and ends with regulation of a downstream cellular process, e.g. transcription. Under conditions of endoplasmic reticulum stress, ATF6 translocates to the Golgi where it is processed by proteases to release a cytoplasmic domain (ATF6f), which operates as a transcriptional activator of many genes required to restore folding capacity.
activating transcription factor 6 signaling in unfolded protein response
endoplasmic reticulum unfolded protein response; ATF6 signaling
The protein catabolic pathway which targets endoplasmic reticulum (ER)-resident proteins for degradation by the cytoplasmic proteasome. It begins with recognition of the ER-resident protein, includes retrotranslocation (dislocation) of the protein from the ER to the cytosol, protein modifications necessary for correct substrate transfer (e.g. ubiquitination), transport of the protein to the proteasome, and ends with degradation of the protein by the cytoplasmic proteasome.
endoplasmic reticulum-associated degradation
ER-associated protein degradation (ERAD) pathways target misfolded ER lumenal proteins (ERAD-L), ER membrane proteins (ERAD-M), and ER proteins with misfolded cytosolic domains (ERAD-C) by recognizing aberrant proteins, retrotranslocating these substrates to the cytosol, followed by substrate ubiquitination and proteosomal-mediated degradation. In contrast the stress-induced homeostatically regulated protein degradation (SHRED) pathway (GO:0120174), although inducible by stress, targets diverse ER membrane, and cytosolic proteins as well as numerous other native proteins in the absence of stress. Stress results in the protease-mediated (Nma111p) generation of a Roq1p cleavage product that then binds to the type-1 active site of Ubr1p, altering its substrate specificity, and leading to the proteasome-mediated degradation of both misfolded and native proteins. Although the SHRED pathway may contain some components in common with ERAD pathways (GO:0036503), such as UBR1, RAD6 and CDC48, other ERAD components, such as HRD1 and DOA10, do not appear to be involved, and as such these pathways are currently considered to be distinct.
A series of molecular signals initiated by the binding of interleukin-2 to a receptor on the surface of a cell, and ending with regulation of a downstream cellular process, e.g. transcription.
interleukin-2-mediated signaling pathway
A series of molecular signals mediated by CCL2 (C-C chemokine CCL2). A series of molecular signals initiated by the binding of the C-C chemokine CCL2 to a C-C chemokine type 2 receptor (CCR2) on the surface of a cell, and ending with regulation of a downstream cellular process, e.g. transcription.
The increase in size or mass of an entire organism, a part of an organism or a cell.
Self-propelled movement of a cell or organism from one location to another.
Any process that modulates the frequency, rate or extent of gene expression; the process is mitotically or meiotically heritable, or is stably self-propagated in the cytoplasm of a resting cell, and does not entail a change in DNA sequence.
regulation of gene expression, epigenetic
The process carried out by a cell that restores the biological activity of an unfolded or misfolded protein, using helper proteins such as chaperones.
Any process that stops, prevents, or reduces the frequency, rate or extent of epidermal growth factor receptor signaling pathway activity.
down regulation of epidermal growth factor receptor signaling pathway
negative regulation of EGF receptor signaling pathway
negative regulation of EGF receptor signalling pathway
negative regulation of EGFR signaling pathway
negative regulation of epidermal growth factor receptor signaling pathway
The chemical reactions and pathways resulting in the formation of cytokines, any of a group of proteins that function to control the survival, growth and differentiation of tissues and cells, and which have autocrine and paracrine activity.
The expansion of a T cell population by cell division. Follows T cell activation.
The expansion of a B cell population by cell division. Follows B cell activation.
The change in morphology and behavior of a mature or immature T cell resulting from exposure to a mitogen, cytokine, chemokine, cellular ligand, or an antigen for which it is specific.
A change in morphology and behavior of a macrophage resulting from exposure to a cytokine, chemokine, cellular ligand, or soluble factor.
The chemical reaction resulting in the formation of any conjugated, water-soluble protein in which the covalently attached nonprotein group consists of a lipid or lipids.
Any process that stops, prevents, or reduces the frequency, rate or extent of the chemical reactions and pathways resulting in the breakdown of a protein by the destruction of the native, active configuration, with or without the hydrolysis of peptide bonds.
negative regulation of protein catabolic process
Any process that results in the repair of damaged RNA.
Tissue regeneration is a subtype of changing material: The regrowth of lost or destroyed tissues.
The chemical reactions and pathways involving any hormone, naturally occurring substances secreted by specialized cells that affects the metabolism or behavior of other cells possessing functional receptors for the hormone.
Cytoplasmic organelles, spherical or oval in shape, that are bounded by a single membrane and contain oxidative enzymes, especially those utilizing hydrogen peroxide (H2O2).
Any biological process involved in the maintenance of an internal steady state.
The transfer of electrons through a series of electron donors and acceptors, generating energy that is ultimately used for synthesis of ATP.
ATP synthesis coupled electron transport
The transfer of electrons through a series of electron donors and acceptors, generating energy that is ultimately used for synthesis of ATP, as it occurs in the mitochondrial inner membrane or chloroplast thylakoid membrane.
mitochondrial ATP synthesis coupled electron transport
Any process that modulates the occurrence or rate of cell death by apoptotic process.
Any process that activates or increases the frequency, rate or extent of cell death by apoptotic process.
positive regulation of apoptotic process
Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process.
negative regulation of apoptotic process
The chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of ubiquitin, and mediated by the proteasome.
proteasome-mediated ubiquitin-dependent protein catabolic process
Organized structure of distinctive morphology and function. Includes the nucleus, mitochondria, plastids, vacuoles, vesicles, ribosomes and the cytoskeleton, and prokaryotic structures such as anammoxosomes and pirellulosomes. Excludes the plasma membrane.
Organized structure of distinctive morphology and function, bounded by a single or double lipid bilayer membrane. Includes the nucleus, mitochondria, plastids, vacuoles, and vesicles. Excludes the plasma membrane.
The internal volume enclosed by the membranes of a particular organelle; includes the volume enclosed by a single organelle membrane, e.g. endoplasmic reticulum lumen, or the volume enclosed by the innermost of the two lipid bilayers of an organelle envelope, e.g. nuclear lumen.
Any process that modulates the frequency, rate or extent of the directed movement of potassium ions (K+) into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
Any process that stops, prevents, or reduces the frequency, rate or extent of the directed movement of potassium ions (K+) into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
negative regulation of potassium ion transport
Any process that activates or increases the frequency, rate or extent of the directed movement of potassium ions (K+) into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
positive regulation of potassium ion transport
Apoptosis triggered by inadequate or inappropriate adherence to substrate e.g. after disruption of the interactions between normal epithelial cells and the extracellular matrix.
An adherent cell-restricted lethal cascade that is ignited by detachment from the matrix and that is characterized by (i) lack of beta1-integrin engagement, (ii) downregulation of EGFR expression, (iii) inhibition of extracellular-regulated kinase 1 (ERK1) signaling, and (iv) overexpression of the BCL-2 family member BIM. It should be noted that in most, if not all, instances, the cell death program ignited by anoikis is executed by the molecular machinery for intrinsic apoptosis. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252826/
The recognition and removal of an apoptotic cell by a neighboring cell or by a phagocyte.
The process of assisting in the disassembly of non-covalent linkages in a protein or protein aggregate, often where the proteins are in a non-functional or denatured state.
chaperone-mediated protein transport involved in chaperone-mediated autophagy subClassOf : has_part some protein unfolding
Any process that modulates the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of precursor metabolites, substances from which energy is derived, and the processes involved in the liberation of energy from these substances.
regulation of generation of precursor metabolites and energy
The aggregation of coloring matter in a particular location in an organism, tissue or cell, occurring in response to some external stimulus.
A series of reactions, mediated by the intracellular serine/threonine kinase protein kinase B (also called AKT), which occurs as a result of a single trigger reaction or compound. PMID:20517722
The addition of an acyl group, any group or radical of the form RCO- where R is an organic group, to a protein amino acid.
Small molecules in GO include monosaccharides but exclude disaccharides and polysaccharides.
The chemical reactions and pathways involving small molecules, any low molecular weight, monomeric, non-encoded molecule.
Any constituent part of a cell, the basic structural and functional unit of all organisms.
The expansion of a dendritic cell population by cell division. A dendritic cell is a cell of hematopoietic origin, typically resident in particular tissues, specialized in the uptake, processing, and transport of antigens to lymph nodes for the purpose of stimulating an immune response via T cell activation.
The cell cycle process by which a cell commits to entering the next cell cycle phase.
A specialized resting state that cells enter in response to cues from the cell's environment. Quiescence is characterized by the absence of cell growth and division, by a reprogramming of global gene expression, and by changes characteristic of the organism and specific cell type. Depending on external conditions, quiescence may persist until cell death or cells may resume cell growth and division. In some cell types or under certain conditions, cellular metabolism may proceed.
The cell cycle process by which a cell in G2 phase commits to M phase.
The cell cycle process by which a cell in G1 phase commits to S phase.
Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens.
Any process that modulates the frequency, rate or extent of the innate immune response, the organism's first line of defense against infection.
The covalent attachment of a palmitoleyl group to a protein.
A change in morphology and behavior of a leukocyte resulting from exposure to a specific antigen, mitogen, cytokine, cellular ligand, or soluble factor.
The process whereby a relatively unspecialized cell acquires specialized features of an adipocyte, an animal connective tissue cell specialized for the synthesis and storage of fat.
The process in which a relatively unspecialized cell acquires specialized features of a myoblast. A myoblast is a mononucleate cell type that, by fusion with other myoblasts, gives rise to the myotubes that eventually develop into striated muscle fibers.
The process in which a mesodermal, bone marrow or neural crest cell acquires specialized features of an endothelial cell, a thin flattened cell. A layer of such cells lines the inside surfaces of body cavities, blood vessels, and lymph vessels, making up the endothelium.
Any process that modulates the frequency, rate or extent of cell differentiation, the process in which relatively unspecialized cells acquire specialized structural and functional features.
Any process that stops, prevents, or reduces the frequency, rate or extent of gluconeogenesis.
Negative regulation of DNA repair is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of DNA repair.
Any process that activates or increases the rate or extent of progression through the cell cycle.
positive regulation of cell cycle progression
positive regulation of progression through cell cycle
Any process that stops, prevents, or reduces the frequency, rate or extent of endocytosis.
Any process that stops, prevents, or reduces the frequency, rate or extent of glycolysis.
negative regulation of glycolytic process
Any process that activates or increases the frequency, rate or extent of the hydrolysis of a peptide bond or bonds within a protein.
Any process that stops, prevents, or reduces the frequency, rate or extent of cellular DNA-templated transcription.
down regulation of transcription, DNA-dependent
down-regulation of transcription, DNA-dependent
negative regulation of transcription, DNA-templated
The chemical reactions and pathways involving ATP, adenosine triphosphate, a universally important coenzyme and enzyme regulator.
The chemical reactions and pathways involving aflatoxin, a fungal metabolite found as a contaminant in moldy grains that induces liver cancer. Aflatoxin induces a G to T transversion at codon 249 of p53, leading to its inactivation. Aflatoxin is converted to a chemical carcinogen by P450.
The chemical reactions and pathways resulting in the breakdown of phosphatidylethanolamine, any of a class of glycerophospholipids in which a phosphatidyl group is esterified to the hydroxyl group of ethanolamine.
phosphatidylethanolamine catabolic process
The chemical reactions and pathways involving phosphatidylcholines, any of a class of glycerophospholipids in which the phosphatidyl group is esterified to the hydroxyl group of choline. They are important constituents of cell membranes.
The chemical reactions and pathways involving phosphatidylglycerols, any of a class of phospholipids in which the phosphatidyl group is esterified to the hydroxyl group of glycerol. They are important constituents of cell membranes.
The chemical reactions and pathways involving phosphatidic acid, any derivative of glycerol phosphate in which both the remaining hydroxyl groups of the glycerol moiety are esterified with fatty acids.
The chemical reactions and pathways resulting in the formation of glycerophospholipids, any derivative of glycerophosphate that contains at least one O-acyl, O-alkyl, or O-alkenyl group attached to the glycerol residue.
glycerophospholipid biosynthetic process
The chemical reactions and pathways resulting in the breakdown of glycerophospholipids, any derivative of glycerophosphate that contains at least one O-acyl, O-alkyl, or O-alkenyl group attached to the glycerol residue.
The chemical reactions and pathways involving phosphatidylinositol, any glycophospholipid in which a sn-glycerol 3-phosphate residue is esterified to the 1-hydroxyl group of 1D-myo-inositol.
The chemical reactions and pathways resulting in the formation of ceramides, any N-acylated sphingoid.
The chemical reactions and pathways resulting in the breakdown of ceramides, any N-acetylated sphingoid.
The directed movement of a drug, a substance used in the diagnosis, treatment or prevention of a disease, out of a cell or organelle.
A change in morphology and behavior of a lymphocyte resulting from exposure to a specific antigen, mitogen, cytokine, chemokine, cellular ligand, or soluble factor.
The expansion of a lymphocyte population by cell division.
Any process that stops, prevents, or reduces the frequency, rate or extent of the release of insulin.
negative regulation of insulin secretion
The phosphorylation by a protein of one or more of its own amino acid residues (cis-autophosphorylation), or residues on an identical protein (trans-autophosphorylation).
Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of lipids.
positive regulation of lipid biosynthetic process
ketone body biosynthetic process is a subtype of generating: A process that synthesizes ketone body resulting in having output (s).
The series of molecular signals generated as a consequence of the hepatocyte growth factor receptor binding to one of its physiological ligands.
hepatocyte growth factor receptor signaling pathway
The directed movement of substances into, out of or within the Golgi apparatus, mediated by vesicles.
A small, subcellular membrane-bounded vesicle containing pigment and/or pigment precursor molecules. Pigment granule biogenesis is poorly understood, as pigment granules are derived from multiple sources including the endoplasmic reticulum, coated vesicles, lysosomes, and endosomes.
Any biological process involved in the maintenance of an internal steady state of a chemical.
The regulated release of cytokines from a cell. Cytokines are any of a group of proteins that function to control the survival, growth and differentiation of tissues and cells, and which have autocrine and paracrine activity.
Any process that modulates the frequency, rate or extent of the immune response, the immunological reaction of an organism to an immunogenic stimulus.
Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus. The process begins with detection of the stimulus and ends with a change in state or activity or the cell or organism.
The movement of a leukocyte within or between different tissues and organs of the body.
Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the breakdown of lipids.
positive regulation of lipid catabolic process
Any process that modulates the frequency, rate or extent of the directed movement of substances (such as macromolecules, small molecules, ions) into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
Any process that stops, prevents, or reduces the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of lipids.
down regulation of lipid biosynthetic process
down-regulation of lipid biosynthetic process
downregulation of lipid biosynthetic process
negative regulation of lipid biosynthesis
negative regulation of lipid biosynthetic process
The directed movement of substances out of the nucleus.
The directed movement of substances into, out of, or within the nucleus.
The directed movement of substances into the nucleus.
The process of binding or confining calcium ions such that they are separated from other components of a biological system.
The process of creating protein polymers, compounds composed of a large number of component monomers; polymeric proteins may be made up of different or identical monomers. Polymerization occurs by the addition of extra monomers to an existing poly- or oligomeric protein.
A process that is carried out at the cellular level that results in the assembly, arrangement of constituent parts, or disassembly of chromosomes, structures composed of a very long molecule of DNA and associated proteins that carries hereditary information. This term covers covalent modifications at the molecular level as well as spatial relationships among the major components of a chromosome.
The process resulting in division and partitioning of components of a cell to form more cells; may or may not be accompanied by the physical separation of a cell into distinct, individually membrane-bounded daughter cells.
http://purl.obolibrary.org/obo/IEV_0003382 (obsolete)
The cell cycle 'gap' phase which is the interval between the completion of DNA segregation (usually by mitosis or meiosis) and the beginning of DNA synthesis.
The cell cycle 'gap' phase which is the interval between the completion of DNA synthesis and the beginning of DNA segregation (usually by mitosis or meiosis).
Note that this term should not be used for direct annotation. If you are trying to make an annotation to x phase, it is likely that the correct annotation is 'regulation of x/y phase transition' or to a process which occurs during the reported phase (i.e mitotic DNA replication for mitotic S-phase). To capture the phase when a specific location or process is observed, the phase term can be used in an annotation extension (PMID:24885854) applied to a cellular component term (with the relation exists_during) or a biological process term (with the relation happens_during).
The cell cycle phase, following G1, during which DNA synthesis takes place.
Any process that modulates the rate or extent of progression through the cell cycle.
regulation of progression through cell cycle
Any process that activates or increases the frequency, rate or extent of cell division.
Any process that stops, prevents, or reduces the frequency, rate or extent of protein kinase B signaling, a series of reactions mediated by the intracellular serine/threonine kinase protein kinase B.
negative regulation of AKT signalling cascade
negative regulation of PKB signaling cascade
negative regulation of protein kinase B signaling
The modification of a xenobiotic substance by the conjugation of glucuronic acid. The resultant glucuronosides are often much more water-soluble than the xenobiotic precursor, enabling efficient excretion.
An organelle consisting of a network of tubules that functions in targeting molecules, such as receptors transporters and lipids, to the plasma membrane.
The process in which a solute is transported across a lipid bilayer, from one side of a membrane to the other.
Transmembrane transport requires transport of a solute across a lipid bilayer. Note that transport through the nuclear pore complex is not transmembrane because the nuclear membrane is a double membrane and is not traversed. For transport through the nuclear pore, consider instead the term 'nucleocytoplasmic transport ; GO:0006913' and its children. Note also that this term is not intended for use in annotating lateral movement within membranes.
Any process involved in the maintenance of an internal steady state of phospholipid within an organism or cell.
A metabolic process that results in the removal or addition of one or more electrons to or from a substance, with or without the concomitant removal or addition of a proton or protons.
The conversion of a differentiated cell of one fate into a differentiated cell of another fate without first undergoing cell division or reversion to a more primitive or stem cell-like fate.
Any process that increases the rate, frequency, or extent of phospholipid catabolism, the chemical reactions and pathways resulting in the breakdown of phospholipids, any lipid containing phosphoric acid as a mono- or diester.
positive regulation of phospholipid catabolic process
A process which results in the assembly, arrangement of constituent parts, or disassembly of a membrane. A membrane is a double layer of lipid molecules that encloses all cells, and, in eukaryotes, many organelles; may be a single or double lipid bilayer; also includes associated proteins.
A cytosolic protein complex that is capable of activating caspase-1.
The membrane invagination process by which an autophagosomal membrane surrounds an object that will be degraded by macroautophagy.
The selective autophagy process in which a damaged lysosome is degraded by macroautophagy.
The aggregation, arrangement and bonding together of a set of macromolecules to form a complex.
The aggregation, arrangement and bonding together of proteins and lipids to form a protein-lipid complex.
The covalent attachment and further modification of carbohydrate residues to a substrate molecule.
A series of molecular signals initiated by the binding of interleukin-6 to a receptor on the surface of a cell, and ending with regulation of a downstream cellular process, e.g. transcription.
interleukin-6-mediated signalling pathway
interleukin-6-mediated signaling pathway
A type of cell death that is morphologically characterized by an increasingly translucent cytoplasm, swelling of organelles, minor ultrastructural modifications of the nucleus (specifically, dilatation of the nuclear membrane and condensation of chromatin into small, irregular, circumscribed patches) and increased cell volume (oncosis), culminating in the disruption of the plasma membrane and subsequent loss of intracellular contents. Necrotic cells do not fragment into discrete corpses as their apoptotic counterparts do. Moreover, their nuclei remain intact and can aggregate and accumulate in necrotic tissues.
Note that the word necrosis has been widely used in earlier literature to describe forms of cell death which are now known by more precise terms, such as apoptosis. Necrosis can occur in a regulated fashion, involving a precise sequence of signals; in this case, consider annotating to GO:0097300 'programmed necrotic cell death' or to its more specific child GO:0070266 'necroptotic process'.
A caspase-1-dependent cell death subroutine that is associated with the generation of pyrogenic mediators such as IL-1beta and IL-18.
The term ‘pyroptosis' has been introduced in 2000 by Brennan and Cookson to functionally describe the peculiar death of macrophages infected by Salmonella typhimurium. Several other bacterial triggers of this atypical cell death modality have been identified, including Shigella flexneri, Listeria monocytogenes, Pseudomonas aeruginosa, Francisella tularensis and the Bacillus anthracis. However, it has become clear that pyroptosis neither constitutes a macrophage-specific process nor a cell death subroutine that only results from bacterial infection. Of note, pyroptotic cells can exhibit apoptotic and/or necrotic morphological features.
Interacting selectively and non-covalently with phosphatidic acid, any of a class of glycerol phosphate in which both the remaining hydroxyl groups of the glycerol moiety are esterified with fatty acids.
A series of molecular signals initiated by the binding of interleukin-1 to a receptor on the surface of a cell, and ending with regulation of a downstream cellular process, e.g. transcription.
interleukin-1-mediated signaling pathway
A protein modification process in which one or more covalently attached groups of a small protein, such as ubiquitin or a ubiquitin-like protein, are removed from a target protein.
protein modification by small protein removal
A protein modification process in which one or more groups of a small protein, such as ubiquitin or a ubiquitin-like protein, are covalently attached to or removed from a target protein.
protein modification by small protein conjugation or removal
The process of removing one or more methyl groups from a molecule.
Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of phospholipids.
positive regulation of phospholipid biosynthetic process
transforming growth factor beta production
The appearance of any member of the transforming growth factor-beta family of cytokines due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels. Transforming growth factor-beta family members include TGF-B1, TGF-B2, and TGF-B3.
chemokine (C-C motif) ligand 4 production
The appearance of chemokine (C-C motif) ligand 4 due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels.
The appearance of chemokine (C-C motif) ligand 1 due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels.
chemokine (C-C motif) ligand 1 production
tumor necrosis factor superfamily cytokine production
The appearance of any member of the TNF superfamily due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels.
The chemical reactions and pathways resulting in the breakdown of misfolded proteins transported from the endoplasmic reticulum and targeted to cytoplasmic proteasomes for degradation.
ER-associated misfolded protein breakdown
ER-associated misfolded protein catabolism
ER-associated misfolded protein degradation
endoplasmic reticulum-associated misfolded protein catabolic process
endoplasmic reticulum-associated misfolded protein catabolism
A process that results in the biosynthesis of constituent macromolecules, assembly, arrangement of constituent parts, or disassembly of a cellular component.
cellular component organization or biogenesis
The cellular DNA metabolic process resulting in the formation of DNA, deoxyribonucleic acid, one of the two main types of nucleic acid, consisting of a long unbranched macromolecule formed from one or two strands of linked deoxyribonucleotides, the 3'-phosphate group of each constituent deoxyribonucleotide being joined in 3',5'-phosphodiester linkage to the 5'-hydroxyl group of the deoxyribose moiety of the next one.
A series of molecular signals transduced with the regulation of transcription of target genes by p53.
signal transduction by p53 class mediator
The multiplication or reproduction of hepatocytes, resulting in the expansion of a cell population. Hepatocytes form the main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules.
The process in which a relatively unspecialized cell acquires the specialized features of a foam cell. A foam cell is a type of cell containing lipids in small vacuoles and typically seen in atherosclerotic lesions, as well as other conditions.
The directed movement of low-density lipoprotein particle from endosomes to lysosomes.
endosome to lysosome transport of low-density lipoprotein particle
A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts of an endoplasmic reticulum membrane.
endoplasmic reticulum membrane organization
A cell aging process stimulated in response to cellular stress, whereby normal cells lose the ability to divide through irreversible cell cycle arrest.
A series of molecular signals in which an intracellular signal is conveyed to trigger the apoptotic death of a cell. The pathway starts with reception of an intracellular signal (e.g. DNA damage, endoplasmic reticulum stress, oxidative stress etc.), and ends when the execution phase of apoptosis is triggered. The intrinsic apoptotic signaling pathway is crucially regulated by permeabilization of the mitochondrial outer membrane (MOMP).
The aggregation, arrangement and bonding together of the apoptosome, a multisubunit protein complex involved in the signaling phase of the apoptotic process.
chemokine (C-X-C motif) ligand 12 production
The appearance of chemokine (C-X-C motif) ligand 12 (CXCL12) due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels.
A programmed cell death characterized morphologically by the presence of smaller than normal mitochondria with condensed mitochondrial membrane densities, reduction or vanishing of mitochondria crista, and outer mitochondrial membrane rupture. Activation of mitochondrial voltage-dependent anion channels and mitogen-activated protein kinases, upregulation of endoplasmic reticulum stress, and inhibition of cystine/glutamate antiporter are involved in the induction of ferroptosis. This process is characterized by the accumulation of lipid peroxidation products and lethal reactive oxygen species (ROS) derived from iron metabolism. Glutathione peroxidase 4 (GPX4), heat shock protein beta-1, and nuclear factor erythroid 2-related factor 2 function as negative regulators of ferroptosis by limiting ROS production and reducing cellular iron uptake, respectively. In contrast, NADPH oxidase and p53 act as positive regulators of ferroptosis by promotion of ROS production and inhibition of expression of SLC7A11 (a specific light-chain subunit of the cystine/glutamate antiporter), respectively. Misregulated ferroptosis has been implicated in multiple physiological and pathological processes.
Any process that reduces or removes the toxicity of a toxic substance. These may include transport of the toxic substance away from sensitive areas and to compartments or complexes whose purpose is sequestration of the toxic substance.
Any protein complex that is part of the inner mitochondrial membrane.
inner mitochondrial membrane protein complex
Any process carried out at the cellular level that reduces or removes the toxicity superoxide radicals or hydrogen peroxide.
Any process that activates or increases the frequency, rate or extent of cellular response to oxidative stress.
positive regulation of cellular response to oxidative stress
Any process that modulates the frequency, rate or extent of macromitophagy.
Any process that activates or increases the frequency, rate or extent of mitophagy.
Interacting selectively and non-covalently with fatty acid derivative.
Interacting selectively and non-covalently with phosphatidylglycerol.
Any process that stops, prevents or reduces the frequency, rate or extent of signal transduction by p53 class mediator.
downregulation of signal transduction by p53 class mediator
Any process that stops, prevents or reduces the frequency, rate or extent of proteasomal protein catabolic process.
negative regulation of proteasomal protein catabolic process
Negative regulation of cell junction assembly is a subtype of negative regulation process: Any process that stops, prevents or reduces the frequency, rate or extent of cell junction assembly.
negative regulation of cell junction assembly
Any DNA replication initiation that is involved in cell cycle DNA replication.
DNA replication initiation involved in cell cycle DNA replication
DNA-dependent DNA replication initiation involved in cell cycle DNA replication
Any process that stops, prevents or reduces the frequency, rate or extent of nuclear cell cycle DNA replication.
down regulation of DNA replication involved in S phase
negative regulation of nuclear cell cycle DNA replication
The directed movement of a proton across a membrane.
Any process that stops, prevents or reduces the frequency, rate or extent of mitochondrial electron transport, NADH to ubiquinone.
negative regulation of mitochondrial electron transport, NADH to ubiquinone
The chemical reaction resulting in the formation of reactive oxygen species, any molecules or ions formed by the incomplete one-electron reduction of oxygen.
reactive oxygen species biosynthetic process
Any process that stops, prevents, or reduces the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of ROS.
negative regulation of reactive oxygen species biosynthetic process
Any process that stops, prevents or reduces the frequency, rate or extent of gap junction assembly.
negative regulation of gap junction assembly
Any process that activates or increases the frequency, rate or extent of glutathione biosynthetic process.
positive regulation of glutathione anabolism
positive regulation of glutathione biosynthesis
positive regulation of glutathione formation
positive regulation of glutathione synthesis
up regulation of glutathione biosynthesis
positive regulation of glutathione biosynthetic process
Any process that activates or increases the frequency, rate or extent of ERAD pathway.
Any process that activates or increases the frequency, rate or extent of protein refolding.
positive regulation of protein refolding
The orderly movement of a macrophage from one site to another.
Any process carried out at the cellular level that reduces or removes the toxicity of a toxic substance. These may include transport of the toxic substance away from sensitive areas and to compartments or complexes whose purpose is sequestration of the toxic substance.
The multiplication or reproduction of hepatic stellate cells, resulting in the expansion of a hepatic stellate cell population. Hepatic stellate cells are found in the perisinusoidal space of the liver, and are capable of multiple roles including storage of retinol, presentation of antigen to T cells (including CD1d-restricted NKT cells), and upon activation, production of extracellular matrix components. This cell type comprises approximately 8-15% of total cells in the liver.
hepatic perisinusoidal cell proliferation
Any process that stops, prevents or reduces the frequency, rate or extent of cellular senescence.
negative regulation of cellular senescence
As a result of binding to Bid, Bax oligomerizes and integrates in the outer mitochondrial membrane that triggers cytochrome c release. Bax mitochondrial membrane insertion triggered by Bid may represent a key step in pathways leading to apoptosis (Eskes et al., 2000)
Activation, translocation and oligomerization of BAX
tBID binds to its mitochondrial partner BAK to release cytochrome c. Activated tBID results in an allosteric activation of BAK. This may induce its intramembranous oligomerization into a pore for cytochrome c efflux.
Activation and oligomerization of BAK protein
Xenobiotics that contain either a carboxylic group or an aromatic hydroxylamine group are possible substrates for amino acid conjugation. Xenobiotics with a carboxylic group conjugate with an amino group of amino acids such as glycine, taurine and glutamine. The hydroxylamine group conjugates with the carboxylic group of amino acids such as proline and serine.
The combination of glutamate, cysteine and ATP is required to form glutathione. The steps involved in the synthesis and recycling of glutathione are outlined (Meister, 1988).
Transport of NF-kappaB, a transcription factor for eukaryotic RNA polymerase II promoters, from the cytoplasm into the nucleus, across the nuclear membrane.
Translocation of NF-kappaB from the cytosol to the nucleus
An abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body.
An increased concentration of glucose in the blood.
A generically dependent continuant that is about some thing.
A measurement datum is an information content entity that is a recording of the output of a measurement such as produced by a device.
granulocyte-macrophage colony-stimulating factor
Tumor necrosis factor ligand superfamily member 6
The TGF-beta superfamily of growth factors regulate many cellular functions, which includes TGF-betas, activins and inhibins, nodal, BMPs and GDFs. TGF-beta/BMP-like proteins are found in various species, including Xenopus, C.elegans and D.melanogaster.
transforming growth factor beta superfamily
BMPs belong to the TGF-beta superfamily. BMP-like molecules have been identified in various species including D.melanogaster (Dpp, Gbb/60A and Scw) and C.elegans.
Glial cell line-derived neurotrophic factor
A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus.
alpha platelet derived growth factor receptor
beta platelet derived growth factor receptor
The vertebrate Fgfr gene family consists of four highly related genes, Fgfr1-4.
transcription factors that are activated by ligands and heterodimerize with RETINOID X RECEPTORS and bind to peroxisome proliferator response elements in the promoter regions of target genes.
Peroxisome proliferator activated receptor
Transforming growth factor-beta receptor
Transforming growth factor-beta receptor type I
Transforming growth factor-beta receptor type II
MHC class Ia (classical) molecules, termed human leukocyte antigen (HLA)-A, HLA-B and HLA-C in humans and H2-K, H2-D and H2-L in mice, are highly polymorphic glycoproteins composed of a single membrane-spanning alpha chain paired with the soluble protein beta2 microglobulin.
major histocompatibility complex class I molecule
MHC class II molecules are composed of membrane-spanning alpha and beta chains.
major histocompatibility complex class II molecule
High affinity immunoglobulin gamma Fc receptor I
Low affinity immunoglobulin gamma FC region receptor III
Low affinity immunoglobulin gamma Fc region receptor II
Integrins comprise a large family of cell surface receptors that are found in many animal species, ranging from sponge to mammals. They are composed of two subunits, alpha and beta, and each alpha beta combination has its own binding specificity and signaling properties.
A role played by the protein contributes to the integrity of the actin cytoskeleton.
Janus kinases (Jaks) are non-receptor tyrosine kinases. In mammals, the family has four members, Jak1, Jak2, Jak3 and Tyrosine kinase 2 (Tyk2). In Drosophila there is only one Jak kinase, Hopscotch (Hop).
Mammals express at least four distinctly regulated groups of MAPKs, ERK-1/2, JNK/SAPK, p38 and ERK5. MAPKs are activated by dual phosphorylation on both tyrosine and threonine residues of a conserved TXY motif.
ERK1 and ERK2 are isoforms of the 'classical' MAPK. Both ERK1 and ERK2 (referred to as ERK1/2) are activated by MAP/ERK kinase 1 (MEK1) and MEK2 (referred to as MEK1/2). MEK1/2 phosphorylates threonine and tyrosine residues in the Thr-Glu-Tyr (TEY) sequence of ERK1/2. Activated ERK1/2 phosphorylates many substrates including transcription factors, such as Elk1 and c-Myc, and protein kinases, such as ribosomal S6 kinase (RSK).
novel PKC isoforms (delta, epsilon, eta and theta) are regulated by DAG and phospholipids.
atypical PKC isoforms (zeta and lambda/iota; PKC-lambda is the mouse ortholog of human PKC-iota) are insensitive to both calcium and DAG.
A family of 90 kDa ribosomal S6 kinases (RSK; also known as p90rsk or MAPK-activated protein kinase-1, MAPKAP-K1). The RSK family of kinases includes three isoforms: RSK1, RSK2 and RSK3 that are encoded by distinct genes and show 75-80% amino acid identity. RSK proteins is regulated by the ERK kinase pathway.
PKA is comprised of two types of subunits. Two catalytic (C) subunits bind to a regulatory (R) subunit dimer to form an inactive holoenzyme complex. Binding of cAMP to the regulatory subunit causes the catalytic subunit to be unleashed.
3-phosphoinositide dependent protein kinase-1
MEK1 and MEK2 phosphorylate and activate ERK1 and ERK2 MAP kinases.
MKK4 and MKK7 phosphorylate and activate JNK MAP kinases.
MKK3 and MKK6 phosphorylate and activate p38 MAP kinases.
Catalysis of the reaction: 1-phosphatidyl-1D-myo-inositol + ATP = a 1-phosphatidyl-1D-myo-inositol 3-phosphate + ADP + 2 H(+).
Phosphatidylinositol 3-kinase p85 regulatory subunit
Phosphatidylinositol 3-kinase p110 catalytic subunit
Receptor-interacting serine/threonine protein kinase
Src homology-2 domain-containing inositol 5'-phosphatase
Src homology 2-containing protein tyrosine phosphatase-1
Src homology 2-containing protein tyrosine phosphatase-2
phosphatidylcholine + H2O = 1-acylglycerophosphocholine + a carboxylate.
The 26S proteasome is a 2.5-MDa molecular machine built from ~31 different subunits, which catalyzes protein degradation. It contains a barrel-shaped proteolytic core complex (the 20S proteasome), capped at one or both ends by 19S regulatory complexes, which recognize ubiquitinated proteins.
Guanine nucleotide-binding protein, alpha subunit
Galphao, the most abundant G protein in mammalian brain, occurs at least in two subforms, i.e., Galphao1 and Galphao2, derived by alternative splicing of the mRNA.
Catalysis role of the reaction: E1 + ubiquitin + ATP--> E1-ubiquitin + AMP + PPi, where the E1-ubiquitin linkage is a thioester bond between the C-terminal glycine of Ub and a sulfhydryl side group of an E1 cysteine residue. This is the first step in a cascade of reactions in which ubiquitin is ultimately added to a protein substrate.
Alternative splicing of the mammal crk gene yields two translation products designated the 28-kDa Crk-I and the 42-kDa Crk-II protein.
The best characterised member of the SH2/SH3 adaptor protein family is Grb2, the human homologue of the nematode Caenorhabditis elegans protein Sem-5. The structure of Grb2 consists of one SH2 domain flanked by two SH3 domains. Recently, further members of the Grb2 family have been isolated, Grap protein and Gads.
The widely expressed Nck is a 47-kDa cytosolic protein exclusively composed of one SH2 and three SH3 domains. Recently, a second member of the Nck family has been isolated (Nck beta/Grb4) which shows 68% amino acid identity to Nck (Nck alpha).
SH2 domain-containing leukocyte protein of 76 kD
Smads is a conserved family of signal transducers. Functionally, Smads fall into three subfamilies:R-Smads; Co-Smads; I-Smads. Eight Smad proteins are encoded in vertebrate, four in Drosophila, and three in C. elegans.
There are five vertebrate R-Smads, Smad1, Smad2, Smad3, Smad5 and Smad8 and they are phosphorylated in response to different types of TGF-beta ligands. Phosphorylated R-Smads can form complexes with Smad4 and positively or negatively regulate transcription. The Mad protein in Drosophila is the ortholog of Smad1/5, whereas dSmad2 is the ortholog of Smad2/3. In C. elegans, sma-2 and sma-3 proved to be homologous to Mad of Drosophila.
Co-Smad forms hetero-oligomers with R-Smads, which in turn translocate into the nucleus and regulate transcriptional responses. Only Smad4 has been identified as a common-mediator Smad in vertebrates. A Smad4 homologue has been identified in Drosophila (Medea) and C. elegans (Sma-4).
Smad6 and Smad7 are inhibitory Smads that serve as decoys interfering with Smad-receptor or Smad-Smad interactions. Inhibitory Smads have also been detected in Drosophila (Dad).
signal tranducers and activators of transcription
There are two STAT1 isoforms (STAT1alpha and STAT1beta) produced by alternative splicing of a single mRNA.
signal transducer and activator of transcription 1
signal transducer and activator of transcription 2
signal transducer and activator of transcription 3
signal transducer and activator of transcription 4
signal transducer and activator of transcription 5a
signal transducer and activator of transcription 5b
signal transducer and activator of transcription 6
Members of this family include p50, p52, p65, c-Rel, v-Rrel, RelB, and the Drosophila proteins, Dorsal, Dif and Relish. Most of these transcription factors bind as homo- and heterodimers to the consensus a DNA sequence motif termed kappa-B.
The NFI family is composed of four members in vertebrates (NFI-A, NFI-B, NFI-C and NFI-X).
The AP-1 (activator protein 1) transcription factor is a dimeric complex that comprises members of the JUN, FOS, ATF (activating transcription factor) and MAF (musculoaponeurotic fibrosarcoma) protein families. The AP-1 complex can therefore form many different combinations of heterodimers and homodimers, and this combination determines the genes that are regulated by AP-1.
BCL-6 belongs to a subset of transcription factors which all have a similar structure composed of an amino-terminal 'POZ' domain and several zinc finger modules at the carboxy-terminus. BCL-6 is highly conserved among vertebrate species. BCL-6 homologues have been identified from human, mouse, frog, and chicken species.
NFAT proteins are a family of transcription factors (NFATC1~C4) whose activation is controlled by calcineurin, a Ca2+-dependent phosphatase.
RGS proteins act as negative regulators of G protein dependent signaling, at least in part, because they stimulate hydrolysis of the GTP bound to activated G alpha subunits.
Drosophila Son of Sevenless (SOS) is homologous to the yeast exchange factor for Ras, CDC25. Mammalian cells contain two closely related homologs of Drosophila SOS: SOS1 and SOS2. Biochemical studies have established that SOS indeed functions as a guanine nucleotide exchange factor for Ras.
guanine nucleotide dissociation inhibitor
cyclin-dependent protein kinase inhibitor
The Bcl-2 family consists of about 20 homologues of important pro- and anti-apoptotic regulators of programmed cell death.
The term 14-3-3 denotes a large family of ~30 kDa acidic proteins that exist primarily as homo- and heterodimers within all eukaryotic cells. Their unusual name refers to their elution position on DEAE-cellulose chromatography and gel electrophoresis during a systematic attempt at classifying bovine brain proteins. In humans, there are seven distinct 14-3-3 genes denoted beta, gamma, epsilon, eta, sigma, tau (theta) and zeta (as well as a number of potential pseudogenes), while yeast and plants contain between 2 and 15 genes.
smooth muscle (enteric type) gamma-actin
Types I, II and III collagens constitute the classical fibrillar collagens and account for 80-90% of all the collagen in the body. Types V and XI collagens are also classified as fibrillar collagens on the basis of thier homology with types I-III collagens.
associate with the surface of fibrils and modify their interactive properties.
fibril associated collagens with interrupted triple helix
Proteoglycans are a diverse family of molecules characterized by a core protein to which is attached one or more glycosaminoglycan (GAG) side-chains.
The MyD118/CR6/Gadd45 gene family (also termed Gadd45b, Gadd45g, Gadd45a) encodes for small (18 kd), evolutionary conserved proteins that are highly homologous to each other (55 57% overall identity at the amino acid level), are highly acidic (pI=4.0 4.2), and are primarily localized within the cell nucleus. MyD118/CR6/GADD45 serve similar, but not identical, functions along different apoptotic and growth inhibitory pathways. They interact with cell cycle proteins.
growth arrest and DNA damage inducible 45
High molecular weight B-cell growth factor
cytotoxic T lymphocyte-associated antigen 8
type I alpha cGMP-dependent protein kinase
type I beta cGMP-dependent protein kinase
Gads is a member of the family of SH2 and SH3 domain containing adaptor proteins that is expressed specifically in hematopoietic cells and functions in the coordination of tyrosine kinase mediated signal transduction. Gads is a unique member of the Grb2 adaptor family.
Alternative splicing of the mammal crk gene yields two translation products designated the 28-kDa Crk-I and the 42-kDa Crk-II protein. The Crk-II protein contains an amino-terminal SH2 domain followed by two SH3 domains. The Crk-I protein does not contain the second SH3 domain. The 36-kDa Crk-L protein is similar to CrkII, but is encoded by a separate gene.
B7.1 (CD80) and B7.2 (CD86) - the two structurally homologous ligands of CD28 - are expressed by professional antigen-presenting cells (APCs), such as dendritic cells (DCs), macrophages and activated B cells, belong to the immunoglobulin superfamily and might exist as dimers and monomers, respectively.
transcription factor for RNA polymerase II
Interleukin-1 receptor-associated kinase 1
Interleukin-1 receptor-associated kinase-2
Interleukin-1 receptor-associated kinase-4
heterotrimer of alpha, beta, gamma subunits. binds the initiator Met-tRNA to the 40S ribosomal subunit. GTP binding to eIF2 is necessary for formation of a stable eIF2:GTP:Met-tRNA ternary complex (TC). Following TC binding to the ribosome triggers GTP hydrolysis by eIF2.
heteropentamer of alpha, beta, gamma, delta, epsilon subunits. guanine nucleotide exchange factor (GEF) activity of eIF2B is necessary to recycle eIF2:GTP to eIF2:GTP.
consists of a core of five non-identical subunits (eIF3a, eIF3b, eIF3c, eIF3i and eIF3g in yeast) and up to six additional subunits in mammals (eIF3d, eIF3e, eIF3f, eIF3h, eIFj and eIF3k). binding to and stabilization of ternary complex, binding to the 40S ribosome, facilitating the binding of mRNA to the 40S ribosome, and promoting dissociation of 40S and 60S ribosomal subunits
eIF4A is a DEADbox helicase that can unwind RNA secondary structure in the cap-proximal region of the mRNA.
eIF4F is a heterotrimeric complex that binds to the cap structure at the 50 end of the mRNA. It is composed of eIF4G and the cap-binding protein eIF4E and the ATPdependent RNA helicase eIF4A.
Mammalian cells contain two isoforms of eIF4G (I&II). eIF4G is a subunit of the heterotrimeric eIF4F complex that binds to the cap structure at the 50 end of the mRNA.
eukaryotic translation initiation factor 4G
Eukaryotic translation initiation factor 4 gamma 3
low density lipoprotein receptor-related protein 3
low density lipoprotein receptor-related protein 4
low density lipoprotein receptor-related protein 5
low density lipoprotein receptor-related protein 6
low density lipoprotein receptor-related protein 8
cAMP-specific 3',5'-cyclic phosphodiesterase 4A
cAMP-specific 3',5'-cyclic phosphodiesterase 4B
cAMP-specific 3',5'-cyclic phosphodiesterase 4C
cAMP-specific 3',5'-cyclic phosphodiesterase 4D
High-affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A
cAMP-specific 3',5'-cyclic phosphodiesterase 7B
cGMP-binding cGMP-specific phosphodiesterase
cGMP-specific 3',5'-cyclic phosphodiesterase
High-affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A
Retinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase gamma-subunit
Rod cGMP-specific 3',5'-cyclic phosphodiesterase alpha-subunit
Rod cGMP-specific 3',5'-cyclic phosphodiesterase beta-subunit
Cone cGMP-specific 3',5'-cyclic phosphodiesterase alpha'-subunit
Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase delta-subunit
Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase gamma-subunit
group XIIB secretory phospholipase A2-like protein
Members of importin beta family (importins/exportins, karyopherins) have been classified as importins or exportins on the basis of the direction they carry their cargo.
chondroitin/dermatan sulfate proteoglycan
basement membrane heparan sulfate proteoglycan
GPI-anchored membrane heparan sulfate proteoglycan
TNF-related apoptosis-inducing ligand receptor 1
Cytochromes of the c type that are found in eukaryotic MITOCHONDRIA. They serve as redox intermediates that accept electrons from MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III and transfer them to MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX IV.
protein inhibitor of neuronal nitric oxide synthase
Gab proteins contain a pleckstrin homology (PH) domain and binding sites for SH2 and SH3 domains. Gab family include mammalian Gab1, Gab2, Gab3, Drosophila Dos, and C. elegans Soc1.
ISGF3 is a heterotrimer of STAT1, STAT2 and p48/ISGF3gamma/IRF9.
STAT1 dimers form the IFNgamma-activated factor (GAF).
Superfamily members of DOCK180 possess the DHR-2 domain and bind to and exchange GDP for GTP on either Rac or Cdc42.
MAPKAPK2 and MAPKAPK3 can be activated by p38 and activated MAPKAPK2/3 can phosphorylate small heat shock protein 27 (HSP27).
A group of compounds derived from ammonia by substituting organic radicals for the hydrogens. (From Grant & Hackh's Chemical Dictionary, 5th ed)
Any compound that contains a constituent sugar, in which the hydroxyl group attached to the first carbon is substituted by an alcoholic, phenolic, or other group. They are named specifically for the sugar contained, such as glucoside (glucose), pentoside (pentose), fructoside (fructose), etc. Upon hydrolysis, a sugar and nonsugar component (aglycone) are formed. (From Dorland, 28th ed; From Miall's Dictionary of Chemistry, 5th ed)
Peptidoglycan (PGN) is a unique and essential component of the cell wall of virtually all bacteria, is not present in eukaryotes, and is an excellent target for the innate immune system.
Involved in cell adhesion. May be involved in the attachment of the actin-based microfilaments to the plasma membrane.
Epac1 (cAMP-GEFI) and Epac2 (cAMP-GEFII) are closely related guanine nucleotide exchange factors (GEFs) for the small GTPase Rap1 and Rap2, which are directly regulated by cAMP.
exchange protein directly activated by cAMP
Antibody molecule (immunoglobulin) consists of four polypeptides chains, two identical light (L) chains and two identical heavy (H) chains. In mammals, there are five classes of antibodies, IgA, IgD, IgE, IgG, and IgM.
A group of naturally occurring amines derived by enzymatic decarboxylation of the natural amino acids. Many have powerful physiological effects (e.g., histamine, serotonin, epinephrine, tyramine). Those derived from aromatic amino acids, and also their synthetic analogs (e.g., amphetamine), are of use in pharmacology.
The MHC class Ib family members include HLA-E, HLA-F, HLA-G and HFE (HLA-H) in humans and gene products from the H2-M, H2-Q and H2-T regions in mice.
MHC class II-like proteins are produced from the class II region of the MHC, HLA-DM (DM) and HLA-DO (DO) (called H2-M, or H2-DM and H2-O in the mouse).
Ins(1,4,5)P3 3-kinases (IP3-3K) are the enzymes responsible for the ATP-dependent conversion of Ins(1,4,5)P3 to Ins(1,3,4,5)P4. Three mammalian isoforms of this enzyme have so far been isolated and designated the A, B and C isoforms.
IGFBPs are a family of secreted proteins that bind IGF with high affinities that are equal to or greater than those of the IGF-IR. Six distinct IGFBPs, designated as IGFBP-1 to -6, have been isolated and characterized from human and a variety of vertebrate species.
insulin-like growth factor-binding protein
FOXO proteins are conserved from worm to human. To date, only one FOXO species has been identified in invertebrates (called dauer formation-16 in Caenorhabditis elegans and dFOXO in Drosophila). In mammals, four subfamily members have been identified: FOXO1 (previously known as FKHR), FOXO3 (previously known as FKHRL1), FOXO4 (previously known as AFX) and FOXO6.
Insulin superfamily genes are ubiquitous in vertebrates, and have been identified in invertebrates, including insects, molluscs, and the nematode Caenorhabditis elegans. Seven members of the insulin superfamily have been identified in humans, including insulin, insulin-like growth factors (IGFs) I and II, relaxins HI and HII, early placenta insulin-like peptide (EPIL), and relaxin-like factor.
Arrow/Lrp5/Lrp6 is a subfamily of the LDL receptor (LDLR) family. Arrow, and also its counterparts LRP5 and LRP6 in mammals and in frogs, appears to function as a coreceptor for Wnt together with the seven-transmembrane receptor Frizzled (frz) in forming the Wnt receptor signaling complex.
Lrp5 and Lrp6 are highly homologous, and are widely co-expressed during embryogenesis and in adult tissues. An orthologue in Drosophila melanogaster is known as arrow, a gene that functions in the canonical Wnt signaling pathway.
The BMP-1/TLD metalloproteinases, conserved in species ranging from Drosophila to humans, act in dorsal-ventral patterning via activation of BMP2, BMP4 (vertebrates) and Dpp (arthropods). There are four mammalian BMP-1/TLD-like proteinases, including BMP-1/mTLD, which is encoded by alternatively spliced mRNA produced by the Bmp1 gene, and TLL1 and TLL2, which are genetically distinct.
bone morphogenetic protein-1/tolloid family
cartilage-derived morphogenetic protein-1
cartilage-derived morphogenetic protein-2
BMP-related proteins can be subdivided into several groups based on their structures and functions. BMP-2, BMP-4, and the Drosophila Dpp form one subgroup.
BMP-related proteins can be subdivided into several groups based on their structures and functions. BMP-5, BMP-6, BMP-7 (OP-1), BMP-8 (OP-2), and the Drosophila Gbb form one subgroup.
BMP-related proteins can be subdivided into several groups based on their structures and functions. GDF-5 (CDMP- 1), GDF-6 (CDMP-2 or BMP-13), and GDF-7 (BMP-12) form one sugroup.
Nucleoside diphoshate kinases (NDKs), an evolutionarily conserved family of proteins, synthesize nucleoside triphosphates from nucleoside diphosphates and ATP. To date, eight human NDK homologues have been identified.
Translation initiation in eukaryotes is an intricate process requiring at least 11 eukaryotic initiation factors (eIFs).
A role played by the entity which catalyses the reaction: acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H+ = long-chain fatty acid + n+1 CoA + n CO2 + 2n NADP+.
Glucose transporter type 1, erythrocyte/brain
Solute carrier family 2, facilitated glucose transporter, member 1
Solute carrier family 2, facilitated glucose transporter, member 2
Glucose transporter type 4, insulin-responsive
Solute carrier family 2, facilitated glucose transporter, member 4
Heterogeneous nuclear ribonucleoprotein I
Epstein-Barr virus small RNA associated protein
Cell surface heparin binding protein HIP
TAX-responsive enhancer element binding protein 107
Heterogeneous nuclear ribonucleoprotein A0
Heterogeneous nuclear ribonucleoprotein A1
Heterogeneous nuclear ribonucleoproteins A2/B1
Heterogeneous nuclear ribonucleoprotein A3
Heterogeneous nuclear ribonucleoproteins C1/C2
Heterogeneous nuclear ribonucleoprotein D0
Heterogeneous nuclear ribonucleoprotein F
Heterogeneous nuclear ribonucleoprotein G
Heterogeneous nuclear ribonucleoprotein H
Heterogeneous nuclear ribonucleoprotein H'
Transformation upregulated nuclear protein
Heterogeneous nuclear ribonucleoprotein K
Heterogeneous nuclear ribonucleoprotein L
Heterogeneous nuclear ribonucleoprotein M
Heterogeneous nuclear ribonucleoprotein R
Heterogenous nuclear ribonucleoprotein U
Transcription elongation factor A protein 1
Transcription elongation factor A protein 1 (Transcription elongation factor S-II protein 1) (Transcription elongation factor TFIIS.o)
Transcription elongation factor S-II protein 1
RNA polymerase II alpha initiation factor
Eukaryotic translation initiation factor 2 alpha subunit
Eukaryotic translation initiation factor 2 subunit 1
translation initiation factor 2 alpha subunit
translation initiation factor 2, subunit 1
Eukaryotic translation initiation factor 2 subunit 2
eukaryotic translation initiation factor 2 beta subunit
eukaryotic translation initiation factor 2, subunit 2
Eukaryotic translation initiation factor 2 subunit 3
eukaryotic translation initiation factor 2 gamma subunit
eukaryotic translation initiation factor 2, subunit 3
Translation initiation factor eIF-2B alpha subunit
eIF-2B GDP-GTP exchange factor, alpha subunit
translation initiation factor 2B alpha subunit
Translation initiation factor eIF-2B beta subunit
eIF-2B GDP-GTP exchange factor, beta subunit
translation initiation factor 2B beta subunit
Translation initiation factor eIF-2B delta subunit
eIF-2B GDP-GTP exchange factor, delta subunit
translation initiation factor 2B delta subunit
Translation initiation factor eIF-2B epsilon subunit
eIF-2B GDP-GTP exchange factor, epsilon subunit
translation initiation factor 2B epsilon subunit
Translation initiation factor eIF-2B gamma subunit
eIF-2B GDP-GTP exchange factor, gamma subunit
translation initiation factor 2B gamma subunit
This subunit is not part of the Saccharomyces cerevisiae core eIF3 complex.
Possible eukaryotic translation initiation factor 3 30 kDa subunit
eukaryotic translation initiation factor 3 subunit 1
Eukaryotic translation initiation factor 3 39 kDa subunit
Translation initiation factor eIF3, p39 subunit
eukaryotic translation initiation factor 3 subunit 2
Eukaryotic translation initiation factor 3 RNA-binding subunit
Translation initiation factor eIF3, p33 subunit
eukaryotic translation initiation factor 3 subunit 4
eukaryotic translation initiation factor 3 subunit 5
Cell cycle regulation and translation initiation protein
Eukaryotic translation initiation factor 3 90 kDa subunit
eukaryotic translation initiation factor 3 subunit 9
eukaryotic translation initiation factor 3 subunit 3
Translation initiation factor eIF3, p110 subunit
eukaryotic translation initiation factor 3 subunit 10
eukaryotic translation initiation factor 3 subunit 7
Eukaryotic translation initiation factor 3 93 kDa subunit
Eukaryotic translation initiation factor 3 subunit 8
Eukaryotic translation initiation factor 3 subunit 6
Eukaryotic translation initiation factor 3 subunit 11
Eukaryotic translation initiation factor 1A, X-chromosomal
Eukaryotic translation initiation factor 1A, Y-chromosomal
eukaryotic translation initiation factor 1A
eukaryotic translation initiation factor 4E
eukaryotic translation initiation factor 4 gamma 1
eukaryotic translation initiation factor 4B
Williams-Beuren syndrome chromosome region 1 protein
eukaryotic translation initiation factor 4H
Eukaryotic translation initiation factor 5
RNA polymerase II transcription factor SIII subunit A1
Transcription elongation factor B polypeptide 3
RNA polymerase II transcription factor SIII subunit C
Transcription elongation factor B polypeptide 1
RNA polymerase II transcription factor SIII subunit B
Transcription elongation factor B polypeptide 2
Wolf-Hirshhorn syndrome candidate 2 protein
Naturally occurring compounds derived from the parent C20 acid, prostanoic acid.
Any icosanoid from that family of C20 polyunsaturated fatty acids and their derivatives generated by leukocytes from arachidonic acid, each member having four double bonds of which three are conjugated.
1D-myo-Inositol 1,3,4,5-tetrakisphosphate
D-myo-Inositol 1,3,4,5-tetrakisphosphate
A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults.
A peptide, of about 33 amino acids, secreted by the upper INTESTINAL MUCOSA and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety.
A gastrointestinal peptide hormone of about 43-amino acids.
A peptide of about 22-amino acids isolated from the DUODENUM. At low pH it inhibits gastric motor activity, whereas at high pH it has a stimulating effect.
A polypeptide hormone that originates in the hypothalamus and stimulates the secretion of prolactin in the pituitary gland.
A tripeptide hormone that originates in the HYPOTHALAMUS and stimulates the secretion of THYROTROPIN from the PITUITARY GLAND. In humans, it also acts as a prolactin-releasing factor. It is also a neurotransmitter in the central nervous system.
Hypothalamic peptide that regulates the synthesis and secretion of GROWTH HORMONE in the anterior pituitary gland.
A peptide hormone of about 22 amino acids. It is derived from PRO-OPIOMELANOCORTIN and has natriuretic activity.
Neuropeptide and gut hormone that helps regulate GASTRIC ACID secretion and motor function. Once released from nerves in the antrum of the STOMACH, the neuropeptide stimulates release of GASTRIN from the GASTRIN-SECRETING CELLS.
A highly basic, 28 amino acid neuropeptide released from intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems and is neuroprotective. It binds special receptors ( RECEPTORS, VASOACTIVE INTESTINAL PEPTIDE).
HORMONES secreted by the gastrointestinal mucosa that affect the timing or the quality of secretion of digestive enzymes, and regulate the motor activity of the digestive system organs.
A 36-amino acid peptide produced by the L cells of the distal small intestine and colon. Peptide YY inhibits gastric and pancreatic secretion.
A peptide hormone of about 27 amino acids from the duodenal mucosa that activates pancreatic secretion and lowers the blood sugar level.
Peptide hormones secreted into the blood by cells in the ISLETS OF LANGERHANS of the pancreas. The alpha cells secrete glucagon; the beta cells secrete insulin; the delta cells secrete somatostatin; and the PP cells secrete pancreatic polypeptide.
A pancreatic peptide hormone of about 29 amino acids secreted by PANCREATIC ALPHA CELLS. It has an important role in regulation of BLOOD GLUCOSE concentration, ketone metabolism, and several other biochemical and physiological processes.
Hormones isolated from the hypothalamus which exercise control over other organs, primarily the pituitary gland. Well-known members include certain pituitary hormone-releasing hormones and pituitary hormone release inhibiting hormones. Vasopressin and oxytocin which are found in the posterior pituitary may also be secreted by the hypothalamus but are not grouped here ( PITUITARY HORMONES, POSTERIOR).
Hormones secreted by the PITUITARY GLAND including those from the anterior lobe (adenohypophysis), the posterior lobe (neurohypophysis), and the ill-defined intermediate lobe.
Hormones produced by the placenta include CHORIONIC GONADOTROPIN, and PLACENTAL LACTOGEN. Not include steroid hormones ( ESTROGENS; PROGESTERONE).
Hormones that stimulate gonadal functions such as GAMETOGENESIS and sex steroid hormone production in the OVARY and the TESTIS. Major gonadotropins are glycoproteins produced primarily by the adenohypophysis ( GONADOTROPINS, PITUITARY) and the placenta ( CHORIONIC GONADOTROPIN). In some species, pituitary PROLACTIN and PLACENTAL LACTOGEN exert some luteotropic activities.
Polypeptide hormones produced in the hypothalamus which inhibit the release of pituitary hormones. Used for PHRIH in general or for which there is no specific heading.
pituitary hormone release inhibiting hormone
Hormones released by one structure (e.g., the hypothalamus or the thyroid gland) that effect the secretion of hormones from the pituitary gland.
A decapeptide hormone released by the hypothalamus. It stimulates the synthesis and secretion of both FOLLICLE STIMULATING HORMONE and luteinizing hormone (LH) from the pituitary gland.
Hormones secreted by the adenohypophysis ( PITUITARY GLAND, ANTERIOR).
The alpha chain of pituitary glycoprotein hormones ( THYROTROPIN; FOLLICLE STIMULATING HORMONE; LUTEINIZING HORMONE) and the placental CHORIONIC GONADOTROPIN. Within a species, the alpha subunits of these four hormones are identical; the distinct functional characteristics of these glycoprotein hormones are determined by the unique beta subunits. Both subunits, the non-covalently bound heterodimers, are required for full biologic activity.
Hormones secreted by the adenohypophysis ( PITUITARY GLAND, ANTERIOR) that stimulate gonadal functions in both males and females. They include FOLLICLE STIMULATING HORMONE that stimulates germ cell maturation ( OOGENESIS; SPERMATOGENESIS), and LUTEINIZING HORMONE that stimulates the production of sex steroids ( ESTROGENS; PROGESTERONE; ANDROGENS).
A major gonadotropin secreted by the adenohypophysis ( PITUITARY GLAND, ANTERIOR). Follicle-stimulating hormone stimulates GAMETOGENESIS and the supporting cells such as the ovarian GRANULOSA CELLS, the testicular SERTOLI CELLS, and LEYDIG CELLS. FSH consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity.
A polypeptide that is secreted by the adenohypophysis ( PITUITARY GLAND, ANTERIOR). Growth hormone, also known as somatotropin, stimulates mitosis, cell differentiation and cell growth. Species-specific growth hormones have been synthesized.
Hormones released from the posterior lobe of the pituitary, including vasopressin (antidiuretic hormone) and oxytocin. They are formed in the neuronal cells of the hypothalamic nuclei and stored in nerve cell endings in the posterior pituitary (neurohypophysis).
A nonapeptide posterior pituitary hormone that causes UTERINE CONTRACTIONS and stimulates MILK EJECTION.
A polypeptide hormone of approximately 25 kDa that is produced by the SYNCYTIOTROPHOBLASTS of the PLACENTA, also known as chorionic somatomammotropin. It has both GROWTH HORMONE and PROLACTIN activities on growth, lactation, and luteal steroid production.
A gonadotropic glycoprotein hormone produced primarily by the PLACENTA. Similar to the pituitary LUTEINIZING HORMONE in structure and function, chorionic gonadotropin is involved in maintaining the CORPUS LUTEUM during pregnancy. CG consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is virtually identical to the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity.
Somatomedin is a group of hormones that is produced, when stimulated by somatotropin (STH), to promote cell growth and division. In this way, they mediate the effect of somatotropin (also known as growth hormone). They have similar biological effects to somatotropin. Three forms include: * somatomedin A, which is another name for insulin-like growth factor 2 * somatomedin B, which is derived from vitronectin * somatomedin C, which is another name for insulin-like growth factor 1
The kinins are pharmacologically active polypeptides released in the tissues and body fluids as a result of the enzymatic action of kallikreins on kininogens. The kinin family includes bradykinin (Arg-Pro-Pro-gly-Phe-Ser-Pro-Phe-Arg), kallidin (Lys-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) and methionyl-lysyl-bradykinin (Met-Lys-Arg-Pro-Pro-Gly-Phe-Arg).
21-Amino-acid peptides produced by vascular endothelial cells and functioning as potent vasoconstrictors. The endothelin family consists of three members, ENDOTHELIN-1; ENDOTHELIN-2; and ENDOTHELIN-3. All three peptides contain 21 amino acids, but vary in amino acid composition. The three peptides produce vasoconstrictor and pressor responses in various parts of the body. However, the quantitative profiles of the pharmacological activities are considerably different among the three isopeptides.
A lactogenic hormone secreted by the adenohypophysis ( PITUITARY GLAND, ANTERIOR). It is a polypeptide of approximately 23 kD. Besides its major action on lactation, in some species prolactin exerts effects on reproduction, maternal behavior, fat metabolism, immunomodulation and osmoregulation. Prolactin receptors are present in the mammary gland, hypothalamus, liver, ovary, testis, and prostate.
An anterior pituitary hormone that stimulates the secretion of CORTICOSTEROIDS and induces growth of the ADRENAL CORTEX. It is a single-chain polypeptide of about 39 amino acids, the first 24 of which are identical in all species. This 24-amino acid segment is said to be responsible for the biological activity of the peptide while the remaining 15-amino acid segment is said to be necessary for any immunological specificity.
A 13-amino acid peptide derived from the ANTERIOR PITUITARY GLAND in man and from the pars intermedia in lower vertebrates. Its amino acid sequence is identical to the first 13 amino acids of ACTH. It influences the formation of deposition of MELANIN in the body.
Lipotropic or pituitary lipotropic hormone. A pituitary hormone mobilizing fat from adipose tissue. Beta-lipotropin is a single-chain peptide of about 90 residues that contains the sequences of endorphins and metenkephalin, and may be a precursor of beta-melanotropin and beta-endorphin. Gamma-lipotropin is shorter and is identical in sequence to the first 58 residues of beta-lipotropin. Both contain sequences common to ACTH and beta-melanotropin.
Peptide hormones secreted by the intermediate lobe of the pituitary that stimulate melanin release and dispersal. Melanocyte-stimulating hormones are also found in the brain where they are presumed to play a signaling role.
A peptide hormone of about 11 amino acids derived from PRO-OPIOMELANOCORTIN that has natriuretic activity.
A glycoprotein hormone secreted by the adenohypophysis ( PITUITARY GLAND, ANTERIOR). Thyrotropin stimulates THYROID GLAND by increasing the iodide transport, synthesis and release of thyroid hormones ( THYROXINE and TRIIODOTHYRONINE). Thyrotropin consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the pituitary glycoprotein hormones (TSH; LUTEINIZING HORMONE and FSH), but the beta subunit is unique and confers its biological specificity.
Octapeptide antidiuretic hormones released by the NEUROHYPOPHYSIS of all vertebrates (chemical composition varies with species). They control water metabolism and balance by regulating LUNG; GILLS; KIDNEY; etc., and water loss, and also contract smooth muscle. They may also be NEUROTRANSMITTERS.
A family of gastrointestinal peptide hormones that excite the secretion of GASTRIC JUICE. They may also occur in the central nervous system where they are presumed to be neurotransmitters.
A 36-amino acid polypeptide secreted by the PANCREAS that has physiological regulatory functions. Plasma pancreatic polypeptide increases after ingestion of food, with age, and in disease states. A lack of pancreatic polypeptide in the ISLETS OF LANGERHANS has been associated with the OBESITY in rats and mice.
A polypeptide hormone produced in the HYPOTHALAMUS, and other tissues and organs. It inhibits the release of growth hormone ( SOMATOTROPIN), and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems.
growth hormone-release inhibiting factor
growth hormone-release inhibiting hormone
ERK5, also known as big MAP kinase 1 (BMK1), is twice the size of other MAPKs. The amino-terminal half contains the kinase domain, which is similar to that of ERK1/2 and has the TEY activation motif, whereas the carboxy-terminal half is unique. MEK5 phosphorylates and activates ERK5, and then the activated ERK5 phosphorylates substrates including myocyte enhancer factor 2 (MEF2).
SH3 domain containing proline rich kinase
Four groups of kinases have been shown to be activated by MAP kinases, ribosomal S6 kinase (RSK also known as MAPKAPK1), MAP kinase-activated protein kinase 2/3 (MAPKAPK2/3), MAP kinase-interacting kinase or MAP kinase signal-integrating kinase (MNK) and MAPKAPK5 (PRAK).
MAPKAPK5 (PRAK) activity is regulated by p38 and activated MAPKAPK5 in turn phosphorylates small heat shock protein 27 (HSP27).
MNK1/2 are regulated by p38 and ERK, but not by JNK. MNK1/2 can phosphorylate eukaryotic initiation factor-4E (eIF-4E).
GO:0005154 epidermal growth factor receptor binding
cellular inhibitor of apoptosis protein-1
cellular inhibitor of apoptosis protein-2
Microtubule- associated protein-2 kinase
Mitogen-activated protein kinase 3 (EC 2.7.1.-) (Extracellular signal- regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase 1) (MAPK 1) (p44-ERK1) (ERT2) (p44-MAPK) (Microtubule- associated protein-2 kinase)
Inhibitor of nuclear factor kappa-B kinase alpha subunit
Inhibitor of nuclear factor kappa B kinase beta subunit
tumor necrosis factor receptor-associated death domain
RIP-associated ICH-1/CED-3-homologous protein with a death domain
caspase and RIP adaptor with death domain
SCF ubiquitin ligase complex is a subtype of molecular complex.
classical PKC isoforms (alpha, betaI, betaII and gamma) are regulated by calcium, diacylglycerol (DAG) and phospholipids.
Interleukin-1 receptor-associated kinase
Smads 2 and 3 serve principally as substrates for the TGFbeta, activin, and Nodal receptors.
Smads 1, 5, and 8 serve principally as substrates for the BMP and anti-Muellerian receptors.
Ca2+/calmodulin-dependent protein kinase
Ca2+/calmodulin-dependent protein kinase II
Fibroblast growth factor homologous factor 3
Fibroblast growth factor homologous factor 1
Fibroblast growth factor homologous factor 2
Fibroblast growth factor homologous factor 4
Tumor-derived hypophosphatemia inducing factor
transmembrane heparan sulfate proteoglycan
Heparan sulfate proteoglycan core protein
Phosphatidylinositol 3-kinase regulatory alpha subunit
Phosphatidylinositol 3-kinase regulatory beta subunit
Phosphatidylinositol 3-kinase catalytic subunit, alpha isoform (EC 2.7.1.137) (PI3-kinase p110 subunit alpha) (PtdIns-3-kinase p110) (PI3K)
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit, alpha isoform
Phosphatidylinositol 3-kinase catalytic subunit, beta isoform (EC 2.7.1.137) (PI3-kinase p110 subunit beta) (PtdIns-3-kinase p110) (PI3K) (PI3Kbeta)
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit, beta isoform
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit, delta isoform
Cell division control protein 2 homolog (EC 2.7.1.-) (p34 protein kinase) (Cyclin-dependent kinase 1) (CDK1)
Cell division control protein 2 homolog (EC 2.7.1.-) (p34 protein kinase) (Cyclin-dependent kinase 1) (CDK1) form
Cell division protein kinase 2 (EC 2.7.1.-)(p33 protein kinase)(CDK2)
Cell division protein kinase 6 (EC 2.7.1.-)(Serine/threonine-protein kinase) (PLSTIRE)(CDK6)
Cell division protein kinase 7 (EC 2.7.1.-) (CDK-activating kinase) (CAK)(TFIIH) (basal transcription factor complex kinase subunit) (39 kDa protein kinase) (P39 Mo15)(STK1)(CAK1)
TFIIH basal transcription factor complex kinase subunit
Ubiquitin-protein ligase E3 Mdm2 (EC 6.3.2.-) (p53-binding protein Mdm2) (Oncoprotein Mdm2) (Double minute 2 protein) (Hdm2)
Insulin-like growth factor I receptor precursor
phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase
cAMP-dependent protein kinase regulatory chain
cAMP-dependent protein kinase catalytic subunit
Neurogenic locus notch homolog protein 3 precursor
T cell-specific transcription factor 1-alpha
low density lipoprotein receptor-related protein
low-density lipoprotein receptor-related protein
low density lipoprotein receptor-related protein 1
low-density lipoprotein receptor-related protein 1
low density lipoprotein (LDL) receptor-related protein 2
Nck, Ash and phospholipase C gamma-binding protein
RAC-alpha serine/threonine protein kinase
RAC-beta serine/threonine protein kinase
RAC-gamma serine/threonine protein kinase
cAMP-dependent protein kinase type I-alpha regulatory chain
cAMP-dependent protein kinase type I-beta regulatory chain
cAMP-dependent protein kinase type II-alpha regulatory chain
cAMP-dependent protein kinase type II-beta regulatory chain
cAMP-dependent protein kinase, alpha-catalytic subunit
cAMP-dependent protein kinase, beta-catalytic subunit
cAMP-dependent protein kinase, gamma-catalytic subunit
reduced oxygenation of body tissues resulting in the decreased pressure of this component of body gases; commonly due to hypoxemia
A synthetic amino acid. Buthionine sulfoximine irreversibly inhibits gamma-glutamylcysteine synthase, thereby depleting cells of glutathione, a metabolite that plays a critical role in protecting cells against oxidative stress, and resulting in free radical-induced apoptosis. Elevated glutathione levels are associated with tumor cell resistance to alkylating agents and platinum compounds. By depleting cells of glutathione, this agent may enhance the in vitro and in vivo cytotoxicities of various chemotherapeutic agents in drug-resistant tumors. Buthionine sulfoximine may also exhibit antiangiogenesis activity. (NCI04)
A family of transmembrane proteins that play a role in the transport of organic anions including bile acids and bilirubin.
Non-neoplastic macrophages that are found in close proximity to or within a tumor mass. [ NCI ]
A laboratory test or analysis of the biological activity of a substance performed by studying its effect in an experimental situation outside the organism, e.g. in the test tube rather than in living systems.
https://ncim.nci.nih.gov/ncimbrowser/ConceptReport.jsp?dictionary=NCI Metathesaurus&code=C1511123
Drug-, radiation-induced, or spontaneous injuries to DNA that introduce deviations from its normal double-helical conformation. These changes include structural distortions that interfere with replication and transcription, as well as point mutations that disrupt base pairs and exert damaging effects on future generations through changes in DNA sequence. If the damage is minor, it can often be repaired (DNA repair); extensive damage can induce apoptosis.
A chemical reaction that uses water to break down a compound.
A pathological process in which normal cells are transformed into malignant cancer cells within a primary tumor.
A pathologic process that involves the transformation of normal cells to a neoplastic state and resulting in polyclonal or monoclonal neoplastic cell proliferation.
The spread or migration of cancer cells from one part of the body (the organ in which it first appeared) to another. The secondary tumor contains cells that are like those in the original (primary) tumor.
The processes which result in cancers in the liver.
Multiplication or reproduction by cell division of a population of identical cells descended from a single progenitor. In immunology, may refer to the clonal proliferation of cells responsive to a specific antigen as part of an immune response. (NCI)
Organic Cation Transporter proteins carry positively charged chemical substances containing covalently bound carbon atoms through solubility barriers, such as lipid membranes or across epithelial layers. After binding substrate, transmembrane transporters often undergo an energy-dependent conformational change that moves the substrate across the membrane with (symport) or against (antiport) concentration gradients.
A usually exophytic mass attached to the underlying tissue by a broad base or a thin stalk. Polyps can be neoplastic or non-neoplastic. Neoplastic polyps usually represent proliferations of the epithelium, and are commonly seen in the gastrointestinal tract. Polyps of the gastrointestinal tract are often called adenomas, are associated with dysplasia, and may eventually transform into carcinomas. Non-neoplastic polyps may be inflammatory, degenerative, or the result of malformations.
The level of degree is high in comparison to medium.
Obstruction or a closure of hollow organ, passageway or vessel; also the transient approximation of the edges of a natural opening; imperforation.
The act of closure or the state of being closed; an obstruction; the relationship between all of the components of the masticatory system in normal function, dysfunction, and parafunction; momentary complete closure of some area in the vocal tract, causing stoppage of the breath and accumulation of pressure.
A set or series of interactions, often forming a network, which biologists have found useful to group together for organizational, historic, biophysical, or other reasons.
a role which inheres in material entities and is realized in the processes of making, enforcing or being defined by legislation or orders issued by a governmental body.
Regulatory agency, Ethics committee, Approval letter; example: Browse these EPA Regulatory Role subtopics http://www.epa.gov/ebtpages/enviregulatoryrole.html Feb 29, 2008
govt agents responsible for creating regulations; proxies for enforcing regulations. CDISC definition: regulatory authorities. Bodies having the power to regulate. NOTE: In the ICH GCP guideline the term includes the authorities that review submitted clinical data and those that conduct inspections. These bodies are sometimes referred to as competent
A planned process with the objective to produce information about the material entity that is the evaluant, by physically examining it or its proxies.
a role which inheres in a person and is realized by the process of being under the care of a physician or health care provider
CDISC definition: patient. Person under a physician's care for a particular disease or condition. NOTE: A subject in a clinical trial is not necessarily a patient, but a patient in a clinical trial is a subject. See also subject, trial subject, healthy volunteer. Often used interchangeably
An imaging assay is an assay to produce a picture of an entity.
pathogen role is a role which inheres in an organism and realized in the process of disease course in the organism bearing host role caused by the organism bearing pathogen role
An imaging assay in which an electrons are used to probe the density, shape and composition of an input material which are detected in an electron microscope and utilized to produce an image of the material.
A cultured cell that has been passaged or derives from a cell that has been passaged in culture.
The term 'secondary cell culture' is generally used in biological texts/protocols to refer to any culture following an initial passage. We include it here because there are often a number of passages between a primary culture and the establishment of a stable, homogenous cell line. Such cultures are considered to be 'secondary cultures' but not 'cell lines' during this intermediate passaging/selection period between their derivation from a 'primary cell culture' and derivation into a 'cell line', which is a more specific type of secondary culture.
A secondary cultured cell has been passaged in culture or is a descendant of such a cell that is derived through propagation in culture.
An organism is material entity that is an individual living system, such as animal, plant, bacteria or virus, that is capable of replicating or reproducing, growth and maintenance in the right environment. An organism may be unicellular or made up, like humans, of many billions of cells divided into specialized tissues and organs. A material entity that is an individual living system, such as animal, plant, bacteria or virus, that is capable of replicating or reproducing, growth and maintenance in the right environment. An organism may be unicellular or made up, like humans, of many billions of cells divided into specialized tissues and organs.
A data item that was generated on the basis of a calculation or logical reasoning
Is an occurrence of a disease caused by an infection
The process of an allergic disease occurring in an organism.
A gene is a material entity that represents the entire DNA sequence required for synthesis of a functional protein or RNA molecule.
Physical and functional unit of heredity, which carries information from one generation to the next. In molecular terms, it is the entire DNA sequence including exons, introns, and noncoding transcription-control regions necessary for production of a functional protein or RNA.
A gene of Homo sapiens that has a protein-coding gene disposition
A gene of Homo sapiens that has a pseudo gene disposition
A gene of Homo sapiens that has a ncRNA gene disposition
A gene of Homo sapiens that has a RNA gene disposition
serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 3
Other designations: alpha-1-antichymotrypsin|cell growth-inhibiting gene 24/25 protein|growth-inhibiting protein 24|growth-inhibiting protein 25|serine (or cysteine) proteinase inhibitor, clade A, member 3|serpin A3
Other designations: ACC-alpha|acetyl-CoA carboxylase 1|acetyl-Coenzyme A carboxylase alpha
Other designations: ACC-beta|acetyl-CoA carboxylase 2|acetyl-Coenzyme A carboxylase beta
Other designations: AOX|acyl-CoA oxidase, straight-chain|acyl-Coenzyme A oxidase 1, palmitoyl|palmitoyl-CoA oxidase|peroxisomal acyl-coenzyme A oxidase 1|peroxisomal fatty acyl-CoA oxidase|straight-chain acyl-CoA oxidase
Other designations: a disintegrin and metalloproteinase domain 8|cell surface antigen MS2|disintegrin and metalloproteinase domain-containing protein 8|human leukocyte differentiation antigen
Other designations: adipophilin|adipose differentiation-related protein|perilipin-2
alcohol dehydrogenase 1B (class I), beta polypeptide
Other designations: ADH, beta subunit|alcohol dehydrogenase 1B|alcohol dehydrogenase 2 (class I), beta polypeptide|alcohol dehydrogenase subunit beta|aldehyde reductase|epididymis secretory protein Li 117
Other designations: AH-receptor|ah receptor|aromatic hydrocarbon receptor|class E basic helix-loop-helix protein 76
v-akt murine thymoma viral oncogene homolog 1
Other designations: PKB alpha|RAC-PK-alpha|RAC-alpha serine/threonine-protein kinase|protein kinase B alpha|proto-oncogene c-Akt|rac protein kinase alpha
v-akt murine thymoma viral oncogene homolog 2
Other designations: PKB beta|RAC-PK-beta|RAC-beta serine/threonine-protein kinase|murine thymoma viral (v-akt) homolog-2|protein kinase Akt-2|protein kinase B beta|rac protein kinase beta
Other designations: 5-aminolevulinate synthase, nonspecific, mitochondrial|5-aminolevulinic acid synthase 1|ALAS-H|delta-ALA synthase 1|delta-aminolevulinate synthase 1|migration-inducing protein 4
aldehyde dehydrogenase 1 family, member A1
Other designations: ALDH class 1|ALHDII|RALDH 1|acetaldehyde dehydrogenase 1|aldehyde dehydrogenase 1, soluble|aldehyde dehydrogenase, liver cytosolic|epididymis luminal protein 12|epididymis luminal protein 9|epididymis secretory sperm binding protein Li 53e|retinal dehydrogenase 1|retinaldehyde dehydrogenase 1
Other designations: aldolase 2|aldolase B, fructose-bisphosphatase|fructose-bisphosphate aldolase B|liver-type aldolase
angiogenin, ribonuclease, RNase A family, 5
Other designations: RNase 5|angiogenin|epididymis luminal protein 168|ribonuclease 5|ribonuclease A A1
Other designations: ANG-1|angiopoietin-1
Other designations: ANG-2|Tie2-ligand|angiopoietin-2|angiopoietin-2B|angiopoietin-2a
solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 4
Other designations: ADP,ATP carrier protein 1|ADP,ATP carrier protein, heart/skeletal muscle|ADP/ATP translocase 1|adenine nucleotide translocator 1 (skeletal muscle)|heart/skeletal muscle ATP/ADP translocator|solute carrier family 25 member 4
Other designations: apoptotic protease-activating factor 1
Other designations: 9.5S alpha-1-glycoprotein|epididymis secretory sperm binding protein Li 92n|pentaxin-related|serum amyloid P-component
Other designations: apo-E|apolipoprotein E3
Other designations: APO-1 cell surface antigen|CD95 antigen|Delta Fas/APO-1/CD95|FAS 827dupA|FAS receptor variant 9|FASLG receptor|Fas (TNF receptor superfamily, member 6)|Fas AMA|TNF receptor superfamily member 6|apoptosis antigen 1|apoptosis-mediating surface antigen FAS|tumor necrosis factor receptor superfamily member 6|tumor necrosis factor receptor superfamily, member 6
Other designations: CD95 ligand|apoptosis (APO-1) antigen ligand 1|apoptosis antigen ligand|fas antigen ligand|tumor necrosis factor (ligand) superfamily, member 6|tumor necrosis factor ligand superfamily member 6
N-acylsphingosine amidohydrolase (acid ceramidase) 1
Other designations: acid CDase|acid ceramidase|acylsphingosine deacylase|putative 32 kDa heart protein
Other designations: ACY-2|aminoacylase 2|aminoacylase-2
Other designations: cAMP-dependent transcription factor ATF-1|cyclic AMP-dependent transcription factor ATF-1
Other designations: cAMP-dependent transcription factor ATF-3|cyclic AMP-dependent transcription factor ATF-3
Other designations: DNA-binding protein TAXREB67|cAMP response element-binding protein 2|cAMP-dependent transcription factor ATF-4|cAMP-responsive element-binding protein 2|cyclic AMP-dependent transcription factor ATF-4|cyclic AMP-responsive element-binding protein 2|tax-responsive enhancer element B67|tax-responsive enhancer element-binding protein 67
Other designations: FRAP-related protein 1|FRAP-related protein-1|MEC1, mitosis entry checkpoint 1, homolog|Rad3 related protein|ataxia telangiectasia and Rad3-related protein|protein kinase ATR|serine/threonine-protein kinase ATR
Other designations: BCL-X/BCL-2 binding protein|BCL2-antagonist of cell death protein|BCL2-binding component 6|BCL2-binding protein|bcl-2-binding component 6|bcl-2-like protein 8|bcl-XL/Bcl-2-associated death promoter|bcl2 antagonist of cell death|bcl2-L-8
Other designations: BCL2-like 7 protein|apoptosis regulator BAK|bcl-2 homologous antagonist/killer|bcl-2-like protein 7|bcl2-L-7|pro-apoptotic protein BAK
Other designations: BCL2-associated X protein omega|BCL2-associated X protein transcript variant delta2|apoptosis regulator BAX|bcl-2-like protein 4|bcl2-L-4
Other designations: B-cell CLL/lymphoma 1|B-cell lymphoma 1 protein|BCL-1 oncogene|G1/S-specific cyclin-D1|PRAD1 oncogene
Other designations: apoptosis regulator Bcl-2|protein phosphatase 1, regulatory subunit 50
Other designations: bcl-2-like protein 5|bcl-2-related protein A1|bcl2-L-5|hematopoietic BCL2-related protein A1|hemopoietic-specific early response protein|protein BFL-1
Other designations: B-cell leukemia/lymphoma 3|B-cell lymphoma 3 protein|B-cell lymphoma 3-encoded protein|BCL-3|chronic lymphatic leukemia protein|proto-oncogene BCL3
betaine--homocysteine S-methyltransferase
Other designations: betaine--homocysteine S-methyltransferase 1|epididymis secretory sperm binding protein Li 61p
Other designations: BH3-interacting domain death agonist|BID isoform ES(1b)|BID isoform L(2)|BID isoform Si6|Human BID coding sequence|apoptic death agonist|desmocollin type 4|p22 BID
Other designations: B-lymphocyte-induced maturation protein 1|BLIMP-1|PR domain zinc finger protein 1|PRDI-binding factor-1|beta-interferon gene positive-regulatory domain I binding factor
Other designations: carbonate dehydratase II|carbonic anhydrase 2|carbonic anhydrase B|carbonic anhydrase C|carbonic dehydratase|epididymis luminal protein 76
Other designations: CA-XII|carbonate dehydratase XII|carbonic anhydrase 12|carbonic dehydratase|tumor antigen HOM-RCC-3.1.3
calcium channel, voltage-dependent, beta 1 subunit
Other designations: calcium channel voltage-dependent subunit beta 1|calcium channel, L type, beta 1 polypeptide|dihydropyridine-sensitive L-type, calcium channel beta-1 subunit|voltage-dependent L-type calcium channel subunit beta-1
solute carrier family 25 (carnitine/acylcarnitine translocase), member 20
Other designations: mitochondrial carnitine/acylcarnitine carrier protein
caspase 1, apoptosis-related cysteine peptidase
Other designations: CASP1 nirs variant 1|IL-1 beta-converting enzyme|IL1B-convertase|caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase)|caspase-1|interleukin 1, beta, convertase|interleukin 1-B converting enzyme
caspase 2, apoptosis-related cysteine peptidase
Other designations: caspase-2|neural precursor cell expressed developmentally down-regulated protein 2|protease ICH-1|protein phosphatase 1, regulatory subunit 57
caspase 3, apoptosis-related cysteine peptidase
Other designations: CASP-3|CPP-32|PARP cleavage protease|SREBP cleavage activity 1|apopain|caspase 3, apoptosis-related cysteine protease|caspase-3|cysteine protease CPP32|procaspase3|protein Yama
caspase 4, apoptosis-related cysteine peptidase
Other designations: CASP-4|ICE(rel)-II|apoptotic cysteine protease Mih1/TX|caspase 4, apoptosis-related cysteine protease|caspase-4|protease ICH-2|protease TX
caspase 5, apoptosis-related cysteine peptidase
Other designations: CASP-5|ICE(rel)-III|TY protease|caspase 5, apoptosis-related cysteine protease|caspase-5|protease ICH-3|protease TY
caspase 6, apoptosis-related cysteine peptidase
Other designations: apoptotic protease MCH-2|caspase 6, apoptosis-related cysteine protease|caspase-6
caspase 7, apoptosis-related cysteine peptidase
Other designations: ICE-like apoptotic protease 3|apoptotic protease MCH-3|caspase 7, apoptosis-related cysteine protease|caspase-7
caspase 8, apoptosis-related cysteine peptidase
Other designations: FADD-homologous ICE/CED-3-like protease|FADD-like ICE|ICE-like apoptotic protease 5|MACH-alpha-1/2/3 protein|MACH-beta-1/2/3/4 protein|MORT1-associated ced-3 homolog|apoptotic cysteine protease|apoptotic protease Mch-5|caspase 8, apoptosis-related cysteine protease|caspase-8
caspase 9, apoptosis-related cysteine peptidase
Other designations: ICE-like apoptotic protease 6|apoptotic protease MCH-6|apoptotic protease activating factor 3|caspase-9|protein phosphatase 1, regulatory subunit 56
caspase 10, apoptosis-related cysteine peptidase
Other designations: CASP-10|FADD-like ICE2|FAS-associated death domain protein interleukin-1B-converting enzyme 2|ICE-like apoptotic protease 4|apoptotic protease MCH-4|caspase 10, apoptosis-related cysteine protease|caspase-10|interleukin-1B-converting enzyme 2
Other designations: extracellular calcium-sensing receptor|parathyroid Ca(2+)-sensing receptor 1|parathyroid cell calcium-sensing receptor 1
Other designations: CD44 antigen|GP90 lymphocyte homing/adhesion receptor|Hermes antigen|cell surface glycoprotein CD44|chondroitin sulfate proteoglycan 8|epican|extracellular matrix receptor III|hematopoietic cell E- and L-selectin ligand|heparan sulfate proteoglycan|homing function and Indian blood group system|hyaluronate receptor|phagocytic glycoprotein 1
Other designations: cell cycle controller CDC2|cell division control protein 2 homolog|cell division cycle 2, G1 to S and G2 to M|cell division protein kinase 1|p34 protein kinase
Other designations: cell division cycle 34 homolog|ubiquitin carrier protein|ubiquitin-conjugating enzyme E2 R1|ubiquitin-conjugating enzyme E2-32 KDA complementing|ubiquitin-conjugating enzyme E2-CDC34|ubiquitin-protein ligase R1
cyclin-dependent kinase inhibitor 1A (p21, Cip1)
Other designations: CDK-interacting protein 1|CDK-interaction protein 1|DNA synthesis inhibitor|cyclin-dependent kinase inhibitor 1|melanoma differentiation associated protein 6|wild-type p53-activated fragment 1
CCAAT/enhancer binding protein (C/EBP), delta
Other designations: CCAAT/enhancer-binding protein delta|c/EBP delta|nuclear factor NF-IL6-beta
Other designations: Centromere autoantigen E (312kD)|centromere-associated protein E|kinesin family member 10|kinesin-related protein CENPE|protein phosphatase 1, regulatory subunit 61
adaptor-related protein complex 1, sigma 1 subunit
Other designations: AP-1 complex subunit sigma-1A|HA1 19 kDa subunit|adapter-related protein complex 1 sigma-1A subunit|adapter-related protein complex 1 subunit sigma-1A|adaptor protein complex AP-1 subunit sigma-1A|clathrin assembly protein complex 1 sigma-1A small chain|clathrin coat assembly protein AP19|clathrin-associated/assembly/adaptor protein, small 1 (19kD)|erythrokeratodermia variabilis 3 (Kamouraska type)|golgi adaptor HA1/AP1 adaptin sigma-1A subunit|sigma1A subunit of AP-1 clathrin adaptor complex|sigma1A-adaptin
Other designations: aging-associated protein 4|apolipoprotein J|complement cytolysis inhibitor|complement lysis inhibitor|complement-associated protein SP-40,40|ku70-binding protein 1|sulfated glycoprotein 2|testosterone-repressed prostate message 2
Other designations: C-C CKR-1|C-C chemokine receptor type 1|CC-CKR-1|CCR-1|LD78 receptor|MIP-1alpha-R|RANTES receptor|RANTES-R|macrophage inflammatory protein 1-alpha receptor
Other designations: C-C CKR-3|C-C chemokine receptor type 3|CC chemokine receptor 3|CCR-3|b-chemokine receptor|eosinophil CC chemokine receptor 3|eosinophil eotaxin receptor
Other designations: C-C CKR-4|C-C chemokine receptor type 4|CCR-4|chemokine (C-C) receptor 4
chemokine (C-C motif) receptor 5 (gene/pseudogene)
Other designations: C-C chemokine receptor type 5|C-C motif chemokine receptor 5 A159A|HIV-1 fusion coreceptor|chemokine receptor CCR5|chemr13
Other designations: C-C chemokine receptor type 6|G protein-coupled receptor 29|G-protein coupled receptor 29|LARC receptor|chemokine (C-C) receptor 6|chemokine receptor-like 3|seven-transmembrane receptor, lymphocyte, 22
Other designations: C-C CKR-7|C-C chemokine receptor type 7|CC chemokine receptor 7|CC-CKR-7|CCR-7|EBV-induced G protein-coupled receptor 1|EBV-induced G-protein coupled receptor 1|Epstein-Barr virus induced G-protein coupled receptor|Epstein-Barr virus induced gene 1|MIP-3 beta receptor|chemokine (C-C) receptor 7|epstein-Barr virus-induced G-protein coupled receptor 1|lymphocyte-specific G protein-coupled peptide receptor
Other designations: C-C chemokine receptor type 8|CC chemokine receptor 8|CC chemokine receptor CHEMR1|CC-chemokine receptor chemr1|chemokine (C-C) receptor 8|chemokine (C-C) receptor-like 2|chemokine receptor-like 1
Other designations: canstatin|collagen alpha-2(IV) chain
Other designations: B-cell-derived protein 1|GC-rich binding factor|GC-rich sites-binding factor GBF|Krueppel-like factor 6|Kruppel-like zinc finger protein Zf9|core promoter element binding protein|core promoter element-binding protein|proto-oncogene BCD1|protooncogene B-cell derived 1|suppression of tumorigenicity 12 (prostate)|suppressor of tumorigenicity 12 protein|transcription factor Zf9
cytochrome c oxidase subunit VIb polypeptide 1 (ubiquitous)
Other designations: COX VIb-1|cytochrome c oxidase subunit 6B1
carnitine palmitoyltransferase 1A (liver)
Other designations: CPT II|carnitine O-palmitoyltransferase 2, mitochondrial|carnitine palmitoyltransferase II
Other designations: activating transcription factor 2 splice variant ATF2-var2|cAMP response element-binding protein CRE-BP1|cAMP responsive element binding protein 2, formerly|cAMP-dependent transcription factor ATF-2|cAMP-responsive element-binding protein 2|cyclic AMP-dependent transcription factor ATF-2|cyclic AMP-responsive element-binding protein 2|histone acetyltransferase ATF2
Other designations: Creb-related protein|cAMP response element-binding protein-related protein|cAMP responsive element binding protein-like 1|cAMP-dependent transcription factor ATF-6 beta|cAMP-responsive element-binding protein-like 1|cyclic AMP-dependent transcription factor ATF-6 beta|protein G13
Other designations: C-reactive protein|pentraxin 1
Other designations: APP secretase|amyloid precursor protein secretase|cathepsin B1|cysteine protease
cytochrome P450, family 1, subfamily A, polypeptide 1
Other designations: CYPIA1|aryl hydrocarbon hydroxylase|cytochrome P1-450, dioxin-inducible|cytochrome P450 1A1|cytochrome P450 form 6|cytochrome P450, subfamily I (aromatic compound-inducible), polypeptide 1|cytochrome P450-C|cytochrome P450-P1|flavoprotein-linked monooxygenase|xenobiotic monooxygenase
cytochrome P450, family 1, subfamily A, polypeptide 2
Other designations: CYPIA2|P450 form 4|aryl hydrocarbon hydroxylase|cytochrome P(3)450|cytochrome P450 1A2|cytochrome P450 4|cytochrome P450, subfamily I (aromatic compound-inducible), polypeptide 2|cytochrome P450-P3|dioxin-inducible P3-450|flavoprotein-linked monooxygenase|microsomal monooxygenase|xenobiotic monooxygenase
cytochrome P450, family 1, subfamily B, polypeptide 1
Other designations: aryl hydrocarbon hydroxylase|cytochrome P450 1B1|cytochrome P450, subfamily I (dioxin-inducible), polypeptide 1 (glaucoma 3, primary infantile)|flavoprotein-linked monooxygenase|microsomal monooxygenase|xenobiotic monooxygenase
cytochrome P450, family 2, subfamily A, polypeptide 6
Other designations: 1,4-cineole 2-exo-monooxygenase|coumarin 7-hydroxylase|cytochrome P450 2A6|cytochrome P450 IIA3|cytochrome P450(I)|cytochrome P450, subfamily IIA (phenobarbital-inducible), polypeptide 6|flavoprotein-linked monooxygenase|xenobiotic monooxygenase
cytochrome P450, family 2, subfamily A, polypeptide 7
Other designations: cytochrome P450 2A7|cytochrome P450 IIA4|cytochrome P450, subfamily IIA (phenobarbital-inducible), polypeptide 7|cytochrome P450IIA4
cytochrome P450, family 3, subfamily A, polypeptide 7
Other designations: aryl hydrocarbon hydroxylase|cytochrome P450 3A7|cytochrome P450, subfamily IIIA, polypeptide 7|cytochrome P450-HFLA|flavoprotein-linked monooxygenase|microsomal monooxygenase|xenobiotic monooxygenase
cytochrome P450, family 2, subfamily A, polypeptide 13
Other designations: cytochrome P450 2A13|cytochrome P450, subfamily IIA (phenobarbital-inducible), polypeptide 13
cytochrome P450, family 2, subfamily B, polypeptide 6
Other designations: 1,4-cineole 2-exo-monooxygenase|cytochrome P450 2B6|cytochrome P450 IIB1|cytochrome P450, subfamily IIB (phenobarbital-inducible), polypeptide 6
cytochrome P450, family 2, subfamily C, polypeptide 19
Other designations: (R)-limonene 6-monooxygenase|(S)-limonene 6-monooxygenase|(S)-limonene 7-monooxygenase|CYPIIC17|CYPIIC19|S-mephenytoin 4-hydroxylase|cytochrome P-450 II C|cytochrome P450 2C19|cytochrome P450, subfamily IIC (mephenytoin 4-hydroxylase), polypeptide 19|cytochrome P450-11A|cytochrome P450-254C|flavoprotein-linked monooxygenase|mephenytoin 4'-hydroxylase|mephenytoin 4-hydroxylase|microsomal monooxygenase|xenobiotic monooxygenase
cytochrome P450, family 2, subfamily C, polypeptide 8
Other designations: P450 form 1|cytochrome P450 2C8|cytochrome P450 IIC2|cytochrome P450 MP-12|cytochrome P450 MP-20|cytochrome P450 form 1|cytochrome P450, subfamily IIC (mephenytoin 4-hydroxylase), polypeptide 8|flavoprotein-linked monooxygenase|microsomal monooxygenase|s-mephenytoin 4-hydroxylase|xenobiotic monooxygenase
cytochrome P450, family 2, subfamily C, polypeptide 9
Other designations: cytochrome P-450 S-mephenytoin 4-hydroxylase|cytochrome P-450MP|cytochrome P450 2C9|cytochrome P450 PB-1|flavoprotein-linked monooxygenase|microsomal monooxygenase|xenobiotic monooxygenase
cytochrome P450, family 2, subfamily C, polypeptide 18
Other designations: (S)-mephenytoin hydroxylase associated cytochrome P450|CYPIIC18|cytochrome P450 2C18|cytochrome P450, subfamily IIC (mephenytoin 4-hydroxylase), polypeptide 17|cytochrome P450, subfamily IIC (mephenytoin 4-hydroxylase), polypeptide 18|cytochrome P450-6B/29C|flavoprotein-linked monooxygenase|microsomal monooxygenase|unspecific monooxygenase
cytochrome P450, family 2, subfamily D, polypeptide 6
Other designations: cytochrome P450 2D6|cytochrome P450, family 2, subfamily D, polypeptide 7 pseudogene 2|cytochrome P450, family 2, subfamily D, polypeptide 8 pseudogene 2|cytochrome P450, subfamily II (debrisoquine, sparteine, etc., -metabolising), polypeptide 7 pseudogene 2|cytochrome P450, subfamily IID (debrisoquine, sparteine, etc., -metabolising), polypeptide 8 pseudogene 2|cytochrome P450, subfamily IID (debrisoquine, sparteine, etc., -metabolizing), polypeptide 6|cytochrome P450, subfamily IID (debrisoquine, sparteine, etc., -metabolizing)-like 1|cytochrome P450-DB1|debrisoquine 4-hydroxylase|flavoprotein-linked monooxygenase|microsomal monooxygenase|xenobiotic monooxygenase
cytochrome P450, family 2, subfamily E, polypeptide 1
Other designations: 4-nitrophenol 2-hydroxylase|CYPIIE1|cytochrome P450 2E1|cytochrome P450, subfamily IIE (ethanol-inducible), polypeptide 1|cytochrome P450-J|flavoprotein-linked monooxygenase|microsomal monooxygenase|xenobiotic monooxygenase
cytochrome P450, family 2, subfamily F, polypeptide 1
Other designations: CYPIIF1|cytochrome P450 2F1|cytochrome P450, subfamily IIF, polypeptide 1|flavoprotein-linked monooxygenase|microsomal monooxygenase|xenobiotic monooxygenase
cytochrome P450, family 2, subfamily J, polypeptide 2
Other designations: CYPIIJ2|arachidonic acid epoxygenase|cytochrome P450 2J2|cytochrome P450, subfamily IIJ (arachidonic acid epoxygenase) polypeptide 2|flavoprotein-linked monooxygenase|microsomal monooxygenase
cytochrome P450, family 3, subfamily A, polypeptide 4
Other designations: 1,8-cineole 2-exo-monooxygenase|P450-III, steroid inducible|albendazole monooxygenase|albendazole sulfoxidase|cytochrome P450 3A3|cytochrome P450 3A4|cytochrome P450 HLp|cytochrome P450 NF-25|cytochrome P450, subfamily IIIA (niphedipine oxidase), polypeptide 3|cytochrome P450, subfamily IIIA (niphedipine oxidase), polypeptide 4|cytochrome P450-PCN1|glucocorticoid-inducible P450|nifedipine oxidase|quinine 3-monooxygenase|taurochenodeoxycholate 6-alpha-hydroxylase
cytochrome P450, family 3, subfamily A, polypeptide 5
Other designations: aryl hydrocarbon hydroxylase|cytochrome P450 3A5|cytochrome P450 HLp2|cytochrome P450, subfamily IIIA (niphedipine oxidase), polypeptide 5|cytochrome P450-PCN3|flavoprotein-linked monooxygenase|microsomal monooxygenase|xenobiotic monooxygenase
cytochrome P450, family 4, subfamily A, polypeptide 11
Other designations: 20-HETE synthase|20-hydroxyeicosatetraenoic acid synthase|CYPIVA11|P450HL-omega|alkane-1 monooxygenase|cytochrome P-450HK-omega|cytochrome P450 4A11|cytochrome P450, subfamily IVA, polypeptide 11|cytochrome P450HL-omega|fatty acid omega-hydroxylase|lauric acid omega-hydroxylase
cytochrome P450, family 4, subfamily B, polypeptide 1
Other designations: cytochrome P450 4B1|cytochrome P450, subfamily IVB, polypeptide 1|cytochrome P450-HP|microsomal monooxygenase
cytochrome P450, family 7, subfamily A, polypeptide 1
Other designations: cholesterol 7-alpha-hydroxylase|cholesterol 7-alpha-monooxygenase|cytochrome P450 7A1|cytochrome P450, subfamily VIIA polypeptide 1
cytochrome P450, family 8, subfamily B, polypeptide 1
Other designations: 7 alpha-hydroxy-4-cholesten-3-one 12-alpha-hydroxylase|7-alpha-hydroxy-4-cholesten-3-one 12-alpha-hydroxylase|7-alpha-hydroxycholest-4-en-3-one 12-alpha-hydroxylase|CYPVIIIB1|cytochrome P450 8B1|cytochrome P450, subfamily VIIIB (sterol 12-alpha-hydroxylase), polypeptide 1|sterol 12-alpha-hydroxylase
cytochrome P450, family 11, subfamily A, polypeptide 1
Other designations: cholesterol 20-22 desmolase|cholesterol monooxygenase (side-chain cleaving)|cholesterol side-chain cleavage enzyme, mitochondrial|cytochrome P450 11A1|cytochrome P450(scc)|cytochrome P450, subfamily XIA (cholesterol side chain cleavage)|cytochrome P450C11A1|steroid 20-22-lyase
cytochrome P450, family 11, subfamily B, polypeptide 1
Other designations: CYPXIB1|cytochrome P-450c11|cytochrome P450 11B1, mitochondrial|cytochrome P450, subfamily XIB (steroid 11-beta-hydroxylase), polypeptide 1|cytochrome P450C11|cytochrome p450 XIB1|steroid 11-beta-hydroxylase|steroid 11-beta-monooxygenase
cytochrome P450, family 11, subfamily B, polypeptide 2
Other designations: aldosterone synthase|aldosterone-synthesizing enzyme|cytochrome P-450Aldo|cytochrome P-450C18|cytochrome P450 11B2, mitochondrial|cytochrome P450, subfamily XIB (steroid 11-beta-hydroxylase), polypeptide 2|mitochondrial cytochrome P450, family 11, subfamily B, polypeptide 2|steroid 11-beta-monooxygenase|steroid 11-beta/18-hydroxylase|steroid 18-hydroxylase, aldosterone synthase, P450C18, P450aldo
cytochrome P450, family 17, subfamily A, polypeptide 1
Other designations: 17-alpha-hydroxyprogesterone aldolase|CYPXVII|cytochrome P450 17A1|cytochrome P450, subfamily XVII (steroid 17-alpha-hydroxylase), adrenal hyperplasia|cytochrome P450-C17|cytochrome P450c17|cytochrome p450 XVIIA1|steroid 17-alpha-hydroxylase/17,20 lyase|steroid 17-alpha-monooxygenase
cytochrome P450, family 19, subfamily A, polypeptide 1
Other designations: aromatase|cytochrome P-450AROM|cytochrome P450 19A1|cytochrome P450, subfamily XIX (aromatization of androgens)|estrogen synthase|estrogen synthetase|flavoprotein-linked monooxygenase|microsomal monooxygenase
cytochrome P450, family 21, subfamily A, polypeptide 2
Other designations: 21-OHase|cytochrome P450 XXI|cytochrome P450, subfamily XXIA (steroid 21-hydroxylase, congenital adrenal hyperplasia), polypeptide 2|cytochrome P450-C21B|steroid 21-hydroxylase|steroid 21-monooxygenase
cytochrome P450, family 24, subfamily A, polypeptide 1
Other designations: 1,25-@dihydroxyvitamin D3 24-hydroxylase|1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial|24-OHase|cytochrome P450 24A1|cytochrome P450, subfamily XXIV (vitamin D 24-hydroxylase)|cytochrome P450-CC24|exo-mitochondrial protein|vitamin D 24-hydroxylase|vitamin D(3) 24-hydroxylase
cytochrome P450, family 26, subfamily A, polypeptide 1
Other designations: P450, retinoic acid-inactivating, 1|cytochrome P450 26A1|cytochrome P450 retinoic acid-inactivating 1|cytochrome P450, subfamily XXVIA, polypeptide 1|cytochrome P450RAI|hP450RAI|retinoic acid 4-hydroxylase|retinoic acid-metabolizing cytochrome
cytochrome P450, family 27, subfamily A, polypeptide 1
Other designations: 5-beta-cholestane-3-alpha, 7-alpha, 12-alpha-triol 26-hydroxylase|5-beta-cholestane-3-alpha, 7-alpha, 12-alpha-triol 27-hydroxylase|5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol 27-hydroxylase|cholestanetriol 26-monooxygenase|cytochrome P-450C27/25|cytochrome P450 27|cytochrome P450, subfamily XXVIIA (steroid 27-hydroxylase, cerebrotendinous xanthomatosis), polypeptide 1|sterol 26-hydroxylase, mitochondrial|sterol 27-hydroxylase|vitamin D(3) 25-hydroxylase
cytochrome P450, family 27, subfamily B, polypeptide 1
Other designations: 1alpha(OH)ase|25 hydroxyvitamin D3-1-alpha hydroxylase|25-OHD-1 alpha-hydroxylase|25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial|VD3 1A hydroxylase|calcidiol 1-monooxygenase|cytochrome P450 subfamily XXVIIB polypeptide 1|cytochrome P450C1 alpha|cytochrome P450VD1-alpha|cytochrome p450 27B1
cytochrome P450, family 51, subfamily A, polypeptide 1
Other designations: CYPLI|cytochrome P450 51A1|cytochrome P450, 51 (lanosterol 14-alpha-demethylase)|cytochrome P450-14DM|cytochrome P45014DM|cytochrome P450LI|lanosterol 14-alpha demethylase|lanosterol 14-alpha-demethylase|sterol 14-alpha demethylase
Dab, mitogen-responsive phosphoprotein, homolog 2 (Drosophila)
Other designations: differentially-expressed protein 2|disabled homolog 2|disabled homolog 2, mitogen-responsive phosphoprotein
growth arrest and DNA-damage-inducible, alpha
Other designations: DDIT-1|DNA damage-inducible transcript 1 protein|DNA damage-inducible transcript-1|DNA-damage-inducible transcript 1|growth arrest and DNA damage-inducible protein GADD45 alpha|growth arrest and DNA-damage-inducible 45 alpha
Other designations: C/EBP zeta|CCAAT/enhancer-binding protein homologous protein|DDIT-3|DNA damage-inducible transcript 3 protein|c/EBP-homologous protein 10|growth arrest and DNA damage-inducible protein GADD153
Other designations: ATP-dependent RNA helicase p54|DEAD (Asp-Glu-Ala-Asp) box polypeptide 6|DEAD box protein 6|DEAD box-6|DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 6 (RNA helicase, 54kD)|oncogene RCK|probable ATP-dependent RNA helicase DDX6
Other designations: DT-diaphorase|NAD(P)H dehydrogenase [quinone] 1|NAD(P)H:Quinone acceptor oxidoreductase type 1|NAD(P)H:menadione oxidoreductase 1|NAD(P)H:quinone oxidoreductase 1|NAD(P)H:quinone oxireductase|azoreductase|diaphorase (NADH/NADPH) (cytochrome b-5 reductase)|diaphorase-4|dioxin-inducible 1|menadione reductase|phylloquinone reductase|quinone reductase 1
Other designations: dihydropyrimidine dehydrogenase [NADP(+)]|dihydrothymine dehydrogenase|dihydrouracil dehydrogenase
Other designations: DSIP-immunoreactive leucine zipper protein|DSIP-immunoreactive peptide|TSC-22 related protein|TSC-22-like protein|TSC-22-related protein|TSC22 domain family protein 3|delta sleep inducing peptide, immunoreactor|delta sleep-inducing peptide immunoreactor|glucocorticoid-induced leucine zipper protein
extracellular matrix protein 2, female organ and adipocyte specific
Other designations: extracellular matrix protein 2|matrix glycoprotein SC1/ECM2
Other designations: delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial|delta3,5-delta2,4-dienoyl-CoA isomerase|dienoyl-CoA isomerase|enoyl Coenzyme A hydratase 1, peroxisomal|peroxisomal enoyl-CoA hydratase 1
Other designations: endothelin-1|preproendothelin-1
eukaryotic translation initiation factor 2D
Other designations: hepatocellular carcinoma-associated antigen 56|ligatin
Other designations: beta-urogastrone|pro-epidermal growth factor
Other designations: avian erythroblastic leukemia viral (v-erb-b) oncogene homolog|cell growth inhibiting protein 40|cell proliferation-inducing protein 61|proto-oncogene c-ErbB-1|receptor tyrosine-protein kinase erbB-1
Other designations: EGR-1|early growth response protein 1|nerve growth factor-induced protein A|transcription factor ETR103|transcription factor Zif268|zinc finger protein 225|zinc finger protein Krox-24
enoyl-CoA, hydratase/3-hydroxyacyl CoA dehydrogenase
Other designations: 3,2-trans-enoyl-CoA isomerase|L-3-hydroxyacyl-CoA dehydrogenase|L-bifunctional protein, peroxisomal|PBE|enoyl-Coenzyme A, hydratase/3-hydroxyacyl Coenzyme A dehydrogenase|peroxisomal bifunctional enzyme|peroxisomal enoyl-CoA hydratase
eukaryotic translation initiation factor 1A, X-linked
Other designations: Putative eukaryotic translation initiation factor 1A|eIF-1A X isoform|eukaryotic translation initiation factor 1A, X chromosome|eukaryotic translation initiation factor 1A, X-chromosomal|eukaryotic translation initiation factor 4C
eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa
Other designations: eIF-2-alpha|eukaryotic translation initiation factor 2 subunit 1|eukaryotic translation initiation factor 2 subunit alpha
eukaryotic translation initiation factor 2B, subunit 1 alpha, 26kDa
Other designations: eIF-2B GDP-GTP exchange factor subunit alpha|translation initiation factor eIF-2B subunit alpha
eukaryotic translation initiation factor 2, subunit 3 gamma, 52kDa
Other designations: eIF-2-gamma X|eIF-2gX|eukaryotic translation initiation factor 2 subunit 3|eukaryotic translation initiation factor 2 subunit gamma X|eukaryotic translation initiation factor 2G
eukaryotic translation initiation factor 4A1
Other designations: ATP-dependent RNA helicase eIF4A-1|eukaryotic initiation factor 4A-I|eukaryotic initiation factor 4AI|eukaryotic translation initiation factor 4A
eukaryotic translation initiation factor 4A2
Other designations: ATP-dependent RNA helicase eIF4A-2|eukaryotic initiation factor 4A-II|eukaryotic translation initiation factor 4A
Other designations: eIF-4E|eIF-4F 25 kDa subunit|eukaryotic translation initiation factor 4E-like 1|mRNA cap-binding protein
eukaryotic translation initiation factor 4E binding protein 1
Other designations: eIF4E-binding protein 1|eukaryotic translation initiation factor 4E-binding protein 1|phosphorylated heat- and acid-stable protein regulated by insulin 1
eukaryotic translation initiation factor 4E binding protein 2
Other designations: 4E-BP2|eIF4E-binding protein 2|eukaryotic translation initiation factor 4E-binding protein 2|phosphorylated, heat and acid stable regulated by insulin protein II
eukaryotic translation initiation factor 4 gamma, 1
Other designations: EIF4-gamma|eIF-4-gamma 1|eucaryotic translation initiation factor 4G|eukaryotic translation initiation factor 4 gamma 1
eukaryotic translation initiation factor 4 gamma, 2
Other designations: DAP-5|aging-associated protein 1|death-associated protein 5|eIF-4-gamma 2|eIF-4G 2|eIF4G 2|eukaryotic translation initiation factor 4 gamma 2|eukaryotic translation initiation factor 4G-like 1
eukaryotic translation initiation factor 5A
Other designations: eIF-4D|eIF-5A-1|eIF-5A1|eukaryotic initiation factor 5A|eukaryotic translation initiation factor 5A-1|rev-binding factor
ELAV like neuron-specific RNA binding protein 4
Other designations: ELAV (embryonic lethal, abnormal vision, Drosophila)-like 4 (Hu antigen D)|ELAV-like protein 4|Embryonic lethal, abnormal vision, Drosophila, homolog of, like-4|Hu antigen D|hu-antigen D|paraneoplastic encephalomyelitis antigen HuD
endoplasmic reticulum to nucleus signaling 1
Other designations: ER to nucleus signalling 1|endoplasmic reticulum-to-nucleus signaling 1|inositol-requiring 1|inositol-requiring enzyme 1|inositol-requiring protein 1|ire1-alpha|protein kinase/endoribonuclease|serine/threonine-protein kinase/endoribonuclease IRE1
v-ets avian erythroblastosis virus E26 oncogene homolog 2
Other designations: oncogene ETS-2|protein C-ets-2|v-ets avian erythroblastosis virus E2 oncogene homolog 2|v-ets erythroblastosis virus E26 oncogene homolog 2
Other designations: anandamide amidohydrolase 1|fatty-acid amide hydrolase 1|oleamide hydrolase 1
Other designations: fatty acid-binding protein 1|fatty acid-binding protein, liver|liver-type fatty acid-binding protein
fatty acid binding protein 5 (psoriasis-associated)
Other designations: epidermal-type fatty acid-binding protein|fatty acid-binding protein, epidermal|psoriasis-associated fatty acid-binding protein homolog
Other designations: FAT tumor suppressor 1|FAT tumor suppressor homolog 1|cadherin ME5|cadherin family member 7|cadherin-related family member 8|cadherin-related tumor suppressor homolog|protein fat homolog|protocadherin Fat 1
membrane-spanning 4-domains, subfamily A, member 2
Other designations: Fc fragment of IgE, high affinity I, receptor for; beta polypeptide|High affinity immunoglobulin epsilon receptor beta-subunit (FcERI) (IgE Fc receptor, beta-subunit) (Fc epsilon receptor I beta-chain)|high affinity IgE receptor beta subunit|high affinity immunoglobulin epsilon receptor subunit beta|igE Fc receptor subunit beta|immunoglobulin E receptor, high affinity, beta polypeptide
Other designations: DNase IV|flap endonuclease 1|maturation factor 1|maturation factor-1
Other designations: basic fibroblast growth factor bFGF|fibroblast growth factor 2|heparin-binding growth factor 2|prostatropin
Other designations: bA397O8.2|fibroblast growth factor homologous factor 4
Other designations: AP3A hydrolase|bis(5'-adenosyl)-triphosphatase|diadenosine 5',5'''-P1,P3-triphosphate hydrolase|dinucleosidetriphosphatase|tumor suppressor protein
Other designations: forkhead box protein O1|forkhead box protein O1A|forkhead, Drosophila, homolog of, in rhabdomyosarcoma
Other designations: cold-insoluble globulin|fibronectin|migration-stimulating factor
Other designations: FTase-alpha|GGTase-I-alpha|farnesyl-protein transferase alpha-subunit|protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha|protein prenyltransferase alpha subunit repeat containing 2|ras proteins prenyltransferase subunit alpha|type I protein geranyl-geranyltransferase alpha subunit
nuclear receptor subfamily 5, group A, member 2
Other designations: CYP7A promoter-binding factor|alpha-1-fetoprotein transcription factor|b1-binding factor, hepatocyte transcription factor which activates enhancer II of hepatitis B virus|fetoprotein-alpha 1 (AFP) transcription factor|hepatocytic transcription factor hB1F-3|liver nuclear receptor homolog-1 variant 2|liver receptor homolog 1|liver receptor homolog-1|nuclear receptor NR5A2|nuclear receptor subfamily 5 group A member 2
glucose-6-phosphatase, catalytic subunit
Other designations: G-6-Pase|G6Pase|G6Pase-alpha|glucose-6-phosphatase|glucose-6-phosphatase alpha
Other designations: glucose-6-phosphate 1-dehydrogenase
Other designations: GRB2-associated binder 1|GRB2-associated-binding protein 1|growth factor receptor bound protein 2-associated protein 1
GA binding protein transcription factor, alpha subunit 60kDa
Other designations: GA binding protein transcription factor alpha subunit 60kDa|GA-binding protein alpha chain|GABP subunit alpha|human nuclear respiratory factor-2 subunit alpha|nuclear respiratory factor 2 alpha subunit|nuclear respiratory factor 2 subunit alpha|transcription factor E4TF1-60
Other designations: GAS-1|Growth arrest-specific gene-1|growth arrest-specific protein 1
glutamine--fructose-6-phosphate transaminase 1
Other designations: D-fructose-6-phosphate amidotransferase 1|glucosamine--fructose-6-phosphate aminotransferase [isomerizing] 1|glutamine--fructose-6-phosphate aminotransferase [isomerizing] 1|glutamine:fructose-6-phosphate amidotransferase 1|hexosephosphate aminotransferase 1
Other designations: GDNF family receptor alpha-1|GDNF receptor alpha-1|GDNFR-alpha-1|GPI-linked anchor protein|Glial cell line-derived neurotrophic factor receptor alpha|PI-linked cell-surface accessory protein|RET ligand 1|TGF-beta related neurotrophic factor receptor 1|TGF-beta-related neurotrophic factor receptor 1
glutamate-cysteine ligase catalytic subunit
glutamate-cysteine ligase, modifier subunit
Other designations: glypican proteoglycan 1|glypican-1
Other designations: C-C CKR-10|C-C chemokine receptor type 10|CC chemokine receptor 10|CC-CKR-10|CCR-10|G protein-coupled receptor 2|G-protein coupled receptor 2
Other designations: C-X-C chemokine receptor type 3|CXC-R3|CXCR-3|G protein-coupled receptor 9|IP-10 receptor|IP10 receptor|Mig receptor|chemokine (C-X-C) receptor 3|interferon-inducible protein 10 receptor
Other designations: G-protein coupled receptor 39
glutathione peroxidase 2 (gastrointestinal)
Other designations: gastrointestinal glutathione peroxidase|glutathione peroxidase 2|glutathione peroxidase-related protein 2
nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor)
Other designations: glucocorticoid nuclear receptor variant 1|glucocorticoid receptor
Other designations: metabotropic glutamate receptor 8
Other designations: GST class-alpha member 3|S-(hydroxyalkyl)glutathione lyase A3|glutathione S-alkyltransferase A3|glutathione S-aralkyltransferase A3|glutathione S-aryltransferase A3|glutathione S-transferase A3|glutathione S-transferase A3-3
Other designations: GST class-mu 3|S-(hydroxyalkyl)glutathione lyase M3|brain GST|brain type mu-glutathione S-transferase|glutathione S-alkyltransferase M3|glutathione S-aralkyltransferase M3|glutathione S-aryltransferase M3|glutathione S-transferase M3 (brain)|glutathione S-transferase Mu 3|glutathione S-transferase, Mu-3|hGSTM3-3
Other designations: H3 histone, family 3A|histone H3.3
hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), beta subunit
Other designations: 2-enoyl-Coenzyme A (CoA) hydratase, beta subunit|3-ketoacyl-Coenzyme A (CoA) thiolase of mitochondrial trifunctional protein, beta subunit|acetyl-CoA acyltransferase|beta-ketothiolase|hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A thiolase/enoyl-Coenzyme A hydratase (trifunctional protein), beta subunit|trifunctional enzyme subunit beta, mitochondrial
Other designations: hematopoietic cell kinase|p59-HCK/p60-HCK|tyrosine-protein kinase HCK
Other designations: MSTP131|glial growth factor|heregulin, alpha (45kD, ERBB2 p185-activator)|neu differentiation factor|neuregulin 1 type IV beta 1a|neuregulin 1 type IV beta 3|pro-NRG1|pro-neuregulin-1, membrane-bound isoform|sensory and motor neuron derived factor
major histocompatibility complex, class II, DP beta 2 (pseudogene)
3-hydroxy-3-methylglutaryl-CoA synthase 1 (soluble)
Other designations: 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase|3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (soluble)|hydroxymethylglutaryl-CoA synthase, cytoplasmic
3-hydroxy-3-methylglutaryl-CoA synthase 2 (mitochondrial)
Other designations: 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2 (mitochondrial)|HMG-CoA synthase|hydroxymethylglutaryl-CoA synthase, mitochondrial
Other designations: HMG-I(Y)|high mobility group protein A1|high mobility group protein HMG-I/HMG-Y|high mobility group protein R|high-mobility group (nonhistone chromosomal) protein isoforms I and Y|nonhistone chromosomal high-mobility group protein HMG-I/HMG-Y
hyaluronan-mediated motility receptor (RHAMM)
Other designations: hyaluronan mediated motility receptor|intracellular hyaluronic acid-binding protein|receptor for hyaluronan-mediated motility
Other designations: heat shock protein, 32-kD|heme oxygenase 1
solute carrier family 29 (equilibrative nucleoside transporter), member 2
Other designations: 36 kDa nucleolar protein HNP36|delayed-early response protein 12|equilibrative NBMPR-insensitive nucleoside transporter|equilibrative nitrobenzylmercaptopurine riboside-insensitive nucleoside transporter|equilibrative nucleoside transporter 2|hydrophobic nucleolar protein, 36 kDa|hydrophobic nucleolar protein, 36kD|nucleoside transporter, ei-type|solute carrier family 29 (nucleoside transporters), member 2|solute carrier family 29 member 2
heterogeneous nuclear ribonucleoprotein A/B
Other designations: ABBP-1|APOBEC1-binding protein 1|apobec-1 binding protein 1|apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1-binding protein 1|hnRNP A/B|hnRNP type A/B protein
DnaJ (Hsp40) homolog, subfamily B, member 2
Other designations: dnaJ homolog subfamily B member 2|dnaJ protein homolog 1|heat shock 40 kDa protein 3|heat shock protein J1|heat shock protein, neuronal DNAJ-like 1
heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa)
Other designations: 78 kDa glucose-regulated protein|endoplasmic reticulum lumenal Ca(2+)-binding protein grp78|epididymis secretory sperm binding protein Li 89n|immunoglobulin heavy chain-binding protein
DnaJ (Hsp40) homolog, subfamily B, member 1
Other designations: DnaJ (Hsp40) homolog, subfmaily B, member 1|dnaJ homolog subfamily B member 1|dnaJ protein homolog 1|hDj-1|heat shock 40 kDa protein 1|heat shock 40kD protein 1|heat shock protein 40|human DnaJ protein 1|radial spoke 16 homolog B
DnaJ (Hsp40) homolog, subfamily C, member 4
Other designations: dnaJ homolog subfamily C member 4|dnaJ-like protein HSPF2|heat shock 40kD protein 2|multiple endocrine neoplasia type 1 candidate protein number 18
Other designations: basement membrane-specific heparan sulfate proteoglycan core protein|endorepellin (domain V region)|perlecan proteoglycan
insulin-like growth factor binding protein 1
Other designations: IBP-1|IGF-binding protein 1|IGFBP-1|alpha-pregnancy-associated endometrial globulin|amniotic fluid binding protein|binding protein-25|binding protein-26|binding protein-28|growth hormone independent-binding protein|insulin-like growth factor-binding protein 1|placental protein 12
insulin-like growth factor binding protein 2, 36kDa
Other designations: IBP-2|IGF-binding protein 2|IGFBP-2|insulin-like growth factor-binding protein 2
insulin-like growth factor binding protein 3
Other designations: IBP-3|IGF-binding protein 3|IGFBP-3|acid stable subunit of the 140 K IGF complex|binding protein 29|binding protein 53|growth hormone-dependent binding protein|insulin-like growth factor-binding protein 3
insulin-like growth factor binding protein 4
Other designations: IBP-4|IGF-binding protein 4|insulin-like growth factor-binding protein 4
insulin-like growth factor binding protein 5
Other designations: IBP-5|IGF-binding protein 5|IGFBP-5|insulin-like growth factor-binding protein 5
insulin-like growth factor binding protein 6
Other designations: IBP-6|IGF binding protein 6|IGF-binding protein 6|IGFBP-6|insulin-like growth factor-binding protein 6
insulin-like growth factor binding protein 7
Other designations: IGF-binding protein 7|IGFBP-rP1|PGI2-stimulating factor|angiomodulin|insulin-like growth factor-binding protein 7|prostacyclin-stimulating factor|tumor-derived adhesion factor
Other designations: CCN family member 1|IBP-10|IGF-binding protein 10|IGFBP-10|cysteine-rich heparin-binding protein 61|cysteine-rich, anigogenic inducer, 61|insulin-like growth factor-binding protein 10|protein CYR61
inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta
Other designations: I-kappa-B kinase 2|I-kappa-B-kinase beta|IKK-B|inhibitor of nuclear factor kappa-B kinase subunit beta|nuclear factor NF-kappa-B inhibitor kinase beta
Other designations: IL-1 alpha|hematopoietin-1|interleukin-1 alpha|preinterleukin 1 alpha|pro-interleukin-1-alpha
Other designations: IL-1 beta|catabolin|interleukin-1 beta|preinterleukin 1 beta|pro-interleukin-1-beta
Other designations: T cell growth factor|aldesleukin|interleukin-2|involved in regulation of T-cell clonal expansion
Other designations: CD122 antigen|IL-2 receptor subunit beta|IL-2R subunit beta|IL-2RB|high affinity IL-2 receptor beta subunit|high affinity IL-2 receptor subunit beta|interleukin 15 receptor, beta|interleukin-2 receptor subunit beta|p75
Other designations: B cell growth factor 1|B_cell stimulatory factor 1|binetrakin|interleukin 4 variant 2|interleukin-4|lymphocyte stimulatory factor 1|pitrakinra
Other designations: B-cell differentiation factor|B-cell stimulatory factor 2|BSF-2|CDF|CTL differentiation factor|IFN-beta-2|hybridoma growth factor|interferon beta-2|interferon, beta 2|interleukin 6 (interferon, beta 2)|interleukin BSF-2|interleukin-6
Other designations: T-cell growth inhibitory factor|cytokine synthesis inhibitory factor|interleukin-10
Other designations: CLMF p35|IL-12, subunit p35|IL35 subunit|NF cell stimulatory factor chain 1|NK cell stimulatory factor chain 1|cytotoxic lymphocyte maturation factor 1, p35|cytotoxic lymphocyte maturation factor 35 kDa subunit|interleukin 12, p35|interleukin 12A (natural killer cell stimulatory factor 1, cytotoxic lymphocyte maturation factor 1, p35)|interleukin-12 alpha chain|interleukin-12 subunit alpha
tumor necrosis factor receptor superfamily, member 9
Other designations: 4-1BB ligand receptor|CD137 antigen|T cell antigen ILA|T-cell antigen 4-1BB homolog|T-cell antigen ILA|homolog of mouse 4-1BB|induced by lymphocyte activation (ILA)|interleukin-activated receptor, homolog of mouse Ly63|receptor protein 4-1BB|tumor necrosis factor receptor superfamily member 9
Other designations: INSIG-1 membrane protein|insulin-induced gene 1 protein
eukaryotic translation initiation factor 3, subunit E
Other designations: eIF-3 p48|eukaryotic translation initiation factor 3 subunit 6|eukaryotic translation initiation factor 3 subunit E|eukaryotic translation initiation factor 3, subunit 6 (48kD)|eukaryotic translation initiation factor 3, subunit 6 48kDa|mammary tumor-associated protein INT6|murine mammary tumor integration site 6 (oncogene homolog)|viral integration site protein INT-6 homolog
Other designations: interferon regulatory factor 1 isoform d78
integrin, beta 1 (fibronectin receptor, beta polypeptide, antigen CD29 includes MDF2, MSK12)
Other designations: glycoprotein IIa|integrin VLA-4 beta subunit|integrin beta-1|very late activation protein, beta polypeptide
integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61)
Other designations: integrin beta-3|platelet membrane glycoprotein IIIa
eukaryotic translation initiation factor 6
Other designations: B4 integrin interactor|eukaryotic translation initiation factor 3A|p27 beta-4 integrin-binding protein
Other designations: Jun activation domain binding protein|activator protein 1|enhancer-binding protein AP1|jun oncogene|p39|proto-oncogene c-Jun|transcription factor AP-1|v-jun avian sarcoma virus 17 oncogene homolog|v-jun sarcoma virus 17 oncogene homolog
Other designations: activator protein 1|transcription factor jun-B
Other designations: JunD-FL isoform|activator protein 1|transcription factor jun-D
potassium large conductance calcium-activated channel, subfamily M, alpha member 1
Other designations: BK channel alpha subunit|BKCA alpha subunit|calcium-activated potassium channel subunit alpha-1|calcium-activated potassium channel, subfamily M subunit alpha-1|hSlo|k(VCA)alpha|maxi-K channel HSLO|slo homolog|slowpoke homolog|stretch-activated Kca channel
Other designations: kinesin-like 2|kinesin-like protein 2|kinesin-like protein KIFC1|kinesin-related protein HSET
Other designations: 14 kDa laminin-binding protein|14 kDa lectin|HBL|HLBP14|HPL|S-Lac lectin 1|beta-galactoside-binding lectin L-14-I|beta-galactoside-binding protein 14kDa|gal-1|galaptin|galectin 1|galectin-1|lactose-binding lectin 1|putative MAPK-activating protein PM12
Other designations: antiangiogenic AK38 protein|apo(a)|apolipoprotein(a)|lp(a)
LPL encodes lipoprotein lipase, which is expressed in heart, muscle, and adipose tissue. LPL functions as a homodimer, and has the dual functions of triglyceride hydrolase and ligand/bridging factor for receptor-mediated lipoprotein uptake. Severe mutations that cause LPL deficiency result in type I hyperlipoproteinemia, while less extreme mutations in LPL are linked to many disorders of lipoprotein metabolism. [provided by RefSeq, Jul 2008]
lanosterol synthase (2,3-oxidosqualene-lanosterol cyclase)
Other designations: 2,3-epoxysqualene--lanosterol cyclase|2,3-epoxysqualene-lanosterol cyclase|hOSC|lanosterol synthase|oxidosqualene--lanosterol cyclase
cytochrome P450, family 4, subfamily F, polypeptide 3
Other designations: CYPIVF3|cytochrome P-450|cytochrome P450 4F3|cytochrome P450, subfamily IVF, polypeptide 3 (leukotriene B4 omega hydroxylase)|cytochrome P450-LTB-omega|leukotriene B4 omega hydroxylase|leukotriene-B(4) 20-monooxygenase 2|leukotriene-B(4) omega-hydroxylase 2|leukotriene-B4 20-monooxygenase
DnaJ (Hsp40) homolog, subfamily B, member 9
Other designations: ER-resident protein ERdj4|dnaJ homolog subfamily B member 9|endoplasmic reticulum DNA J domain-containing protein 4|endoplasmic reticulum DnaJ homolog 4|microvascular endothelial differentiation gene 1 protein
MDM2 oncogene, E3 ubiquitin protein ligase
Other designations: E3 ubiquitin-protein ligase Mdm2|Mdm2, p53 E3 ubiquitin protein ligase homolog|Mdm2, transformed 3T3 cell double minute 2, p53 binding protein|double minute 2, human homolog of; p53-binding protein|oncoprotein Mdm2
malic enzyme 1, NADP(+)-dependent, cytosolic
Other designations: Malic enzyme, cytoplasmic|NADP-ME|NADP-dependent malic enzyme|malate dehydrogenase|malic enzyme 1, soluble|pyruvic-malic carboxylase
matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase)
Other designations: 72 kDa gelatinase|72 kDa type IV collagenase|MMP-2|collagenase type IV-A|gelatinase A|matrix metalloproteinase-2|matrix metalloproteinase-II|neutrophil gelatinase
matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase)
Other designations: 92 kDa gelatinase|92 kDa type IV collagenase|macrophage gelatinase|matrix metalloproteinase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase)|matrix metalloproteinase-9|type V collagenase
Other designations: CD200 antigen|MRC OX-2 antigen|OX-2 membrane glycoprotein|antigen identified by monoclonal antibody MRC OX-2
v-myb avian myeloblastosis viral oncogene homolog-like 2
Other designations: myb-like protein 2|myb-related protein B|v-myb myeloblastosis viral oncogene homolog-like 2
v-myc avian myelocytomatosis viral oncogene homolog
Other designations: avian myelocytomatosis viral oncogene homolog|class E basic helix-loop-helix protein 39|myc proto-oncogene protein|myc-related translation/localization regulatory factor|proto-oncogene c-Myc|transcription factor p64|v-myc myelocytomatosis viral oncogene homolog
v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog
Other designations: N-myc proto-oncogene protein|class E basic helix-loop-helix protein 37|neuroblastoma MYC oncogene|neuroblastoma-derived v-myc avian myelocytomatosis viral related oncogene|oncogene NMYC|pp65/67
growth arrest and DNA-damage-inducible, beta
Other designations: growth arrest and DNA damage-inducible protein GADD45 beta|myeloid differentiation primary response protein MyD118|negative growth regulatory protein MyD118
Other designations: HSP22-like protein interacting protein|NAP-1 related protein|NAP-1-related protein|hNRP
Other designations: light molecular weight neurofilament protein|neurofilament light polypeptide|neurofilament protein, light chain|neurofilament subunit NF-L|neurofilament triplet L protein|neurofilament, light polypeptide 68kDa
Other designations: neurofibromatosis-related protein NF-1|neurofibromin
nuclear factor of kappa light polypeptide gene enhancer in B-cells 1
Other designations: DNA binding factor KBF1|DNA-binding factor KBF1|NF-kappabeta|nuclear factor NF-kappa-B p105 subunit|nuclear factor NF-kappa-B p50 subunit|nuclear factor kappa-B DNA binding subunit
nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (p49/p100)
Other designations: DNA-binding factor KBF2|NFKB, p52/p100 subunit|lymphocyte translocation chromosome 10 protein|nuclear factor Kappa-B, subunit 2|nuclear factor NF-kappa-B p100 subunit|nuclear factor of Kappa light chain gene enhancer in B cells 2|oncogene Lyt-10|transcription factor NFKB2
NME/NM23 nucleoside diphosphate kinase 1
Other designations: NDP kinase A|granzyme A-activated DNase|metastasis inhibition factor nm23|non-metastatic cells 1, protein (NM23A) expressed in|nucleoside diphosphate kinase A|tumor metastatic process-associated protein
Other designations: DNA-binding protein NEFA|epididymis secretory protein Li 109|gastric cancer antigen Zg4|nesfatin-1|nucleobindin-2|nucleobinding 2|prepronefastin|prepronesfatin
Other designations: cellular thyroid hormone-binding protein|collagen prolyl 4-hydroxylase beta|glutathione-insulin transhydrogenase|p55|procollagen-proline, 2-oxoglutarate 4-dioxygenase (proline 4-hydroxylase), beta polypeptide|prolyl 4-hydroxylase subunit beta|protein disulfide isomerase family A, member 1|protein disulfide isomerase-associated 1|protein disulfide isomerase/oxidoreductase|protein disulfide-isomerase|protocollagen hydroxylase|thyroid hormone-binding protein p55
propionyl CoA carboxylase, alpha polypeptide
Other designations: PCCase alpha subunit|pccA complementation group|propanoyl-CoA:carbon dioxide ligase alpha subunit|propionyl Coenzyme A carboxylase, alpha polypeptide|propionyl-CoA carboxylase alpha chain, mitochondrial
Other designations: cadherin superfamily protein VR4-11|protocadherin-9
phosphoenolpyruvate carboxykinase 1 (soluble)
Other designations: PEP carboxykinase|phosphoenolpyruvate carboxykinase, cytosolic|phosphoenolpyruvate carboxykinase, cytosolic [GTP]|phosphoenolpyruvate carboxylase|phosphopyruvate carboxylase
phosphoenolpyruvate carboxykinase 2 (mitochondrial)
Other designations: PEP carboxykinase|phosphoenolpyruvate carboxykinase [GTP], mitochondrial|phosphoenolpyruvate carboxylase|phosphopyruvate carboxylase
Other designations: cGMP-dependent 3',5'-cyclic phosphodiesterase|cGMP-stimulated phosphodiesterase 1|cGMP-stimulated phosphodiesterase 4|cyclic GMP-stimulated phosphodiesterase
pyruvate dehydrogenase kinase, isozyme 4
Other designations: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial|[Pyruvate dehydrogenase [lipoamide]] kinase isozyme 4, mitochondrial|pyruvate dehydrogenase kinase, isoenzyme 4|pyruvate dehydrogenase, lipoamide, kinase isozyme 4, mitochondrial
Other designations: nuclear receptor subfamily 3 group C member 3
phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2 gamma
Other designations: PTDINS-3-kinase C2 gamma|phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit gamma|phosphatidylinositol-4-phosphate 3-kinase C2 domain-containing gamma polypeptide|phosphatidylinositol-4-phosphate 3-kinase C2 domain-containing subunit gamma|phosphoinositide-3-kinase, class 2, gamma polypeptide|ptdIns-3-kinase C2 subunit gamma
phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha
Other designations: PI3-kinase p110 subunit alpha|PI3K-alpha|phosphatidylinositol 3-kinase, catalytic, 110-KD, alpha|phosphatidylinositol 3-kinase, catalytic, alpha polypeptide|phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform|phosphatidylinositol-4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha|phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit, alpha isoform|phosphoinositide-3-kinase, catalytic, alpha polypeptide|ptdIns-3-kinase subunit p110-alpha|serine/threonine protein kinase PIK3CA
Other designations: ALL1-responsive protein ARP1|all1-responsive gene 1|homeobox protein PITX2|paired-like homeodomain transcription factor 2|pituitary homeobox 2|rieg bicoid-related homeobox transcription factor 1|solurshin
Other designations: phosphatidylcholine 2-acylhydrolase 1B|phospholipase A2
Other designations: Ca2+-dependent phospholipase A2|calcium-dependent phospholipase A2|phosphatidylcholine 2-acylhydrolase 5
Other designations: cardiac phospholamban
phorbol-12-myristate-13-acetate-induced protein 1
Other designations: PMA-induced protein 1|adult T cell leukemia-derived PMA-responsive|immediate-early-response protein APR|protein Noxa
Other designations: PMM 1|PMMH-22|brain glucose-1,6-bisphosphatase
Other designations: NADPH--cytochrome P450 reductase|NADPH-dependent cytochrome P450 reductase
Other designations: POU domain, class 6, transcription factor 1|brain-5|brain-specific homeobox/POU domain protein 5|brn-5|mPOU homeobox protein
peroxisome proliferator-activated receptor alpha
Other designations: PPAR-alpha|nuclear receptor subfamily 1 group C member 1|peroxisome proliferative activated receptor, alpha|peroxisome proliferator-activated nuclear receptor alpha variant 3
protein kinase, AMP-activated, alpha 1 catalytic subunit
Other designations: 5'-AMP-activated protein kinase catalytic subunit alpha-1|5'-AMP-activated protein kinase, catalytic alpha-1 chain|ACACA kinase|AMP -activate kinase alpha 1 subunit|AMP-activated protein kinase, catalytic, alpha-1|AMPK alpha 1|AMPK subunit alpha-1|HMGCR kinase|acetyl-CoA carboxylase kinase|hydroxymethylglutaryl-CoA reductase kinase|tau-protein kinase PRKAA1
protein kinase (cAMP-dependent, catalytic) inhibitor beta
Other designations: PKI-beta|cAMP-dependent protein kinase inhibitor 2|cAMP-dependent protein kinase inhibitor beta
Other designations: PKC-B|protein kinase C beta type|protein kinase C, beta 1 polypeptide
Other designations: JUN N-terminal kinase|MAP kinase 8|c-Jun N-terminal kinase 1|mitogen-activated protein kinase 8 isoform JNK1 alpha1|mitogen-activated protein kinase 8 isoform JNK1 beta2|stress-activated protein kinase 1|stress-activated protein kinase 1c
mitogen-activated protein kinase kinase 6
Other designations: MAPK/ERK kinase 6|MAPKK 6|MEK 6|SAPK kinase 3|dual specificity mitogen-activated protein kinase kinase 6|protein kinase, mitogen-activated, kinase 6 (MAP kinase kinase 6)|stress-activated protein kinase kinase 3
eukaryotic translation initiation factor 2-alpha kinase 2
Other designations: P1/eIF-2A protein kinase|double stranded RNA activated protein kinase|eIF-2A protein kinase 2|interferon-induced, double-stranded RNA-activated protein kinase|interferon-inducible elF2alpha kinase|p68 kinase|protein kinase, interferon-inducible double stranded RNA dependent|tyrosine-protein kinase EIF2AK2
DnaJ (Hsp40) homolog, subfamily C, member 3
Other designations: ER-resident protein ERdj6|dnaJ homolog subfamily C member 3|endoplasmic reticulum DNA J domain-containing protein 6|endoplasmic reticulum DnaJ protein 6|interferon-induced, double-stranded RNA-activated protein kinase inhibitor|protein kinase inhibitor of 58 kDa|protein kinase inhibitor p58|protein-kinase, interferon-inducible double stranded RNA dependent inhibitor
prostaglandin E receptor 4 (subtype EP4)
Other designations: PGE receptor EP4 subtype|PGE receptor, EP4 subtype|PGE2 receptor EP4 subtype|prostaglandin E2 receptor EP4 subtype|prostanoid EP4 receptor
protein tyrosine phosphatase, non-receptor type 4 (megakaryocyte)
Other designations: PTPase-MEG1|megakaryocyte phosphatase|megakaryocyte protein-tyrosine phosphatase|protein tyrosine phosphatase MEG1|protein-tyrosine phosphatase MEG1|tyrosine-protein phosphatase non-receptor type 4
protein tyrosine phosphatase, non-receptor type 6
Other designations: hematopoietic cell phosphatase|hematopoietic cell protein-tyrosine phosphatase|protein-tyrosine phosphatase 1C|protein-tyrosine phosphatase SHP-1|tyrosine-protein phosphatase non-receptor type 6
olfactory receptor family 3 subfamily A member 4 pseudogene
Other designations: 33 kDa housekeeping protein|housekeeping gene, 33kD|peroxin-19|peroxisomal farnesylated protein
Other designations: RAS-associated protein RAB13|cell growth-inhibiting gene 4 protein|growth-inhibiting gene 4 protein|ras-related protein Rab-13
Other designations: DNA repair protein RAD51 homolog 2|RAD51 homolog B|RecA-like protein|recombination repair protein
Other designations: 107 kDa retinoblastoma-associated protein|cellular protein 107|retinoblastoma-like 1 (p107)|retinoblastoma-like protein 1
regulatory factor X, 3 (influences HLA class II expression)
Other designations: DNA binding protein RFX3|transcription factor RFX3
Other designations: E3 ubiquitin-protein ligase RING2|HIP2-interacting protein 3|RING finger protein 1B|RING finger protein BAP-1|huntingtin-interacting protein 2-interacting protein 3|protein DinG
Other designations: O27.1.1|bromodomain-containing 2|bromodomain-containing protein 2|female sterile homeotic-related gene 1|really interesting new gene 3 protein
Rho-associated, coiled-coil containing protein kinase 1
Other designations: Rho kinase|p160 ROCK-1|p160-ROCK|renal carcinoma antigen NY-REN-35|rho-associated protein kinase 1|rho-associated, coiled-coil-containing protein kinase 1|rho-associated, coiled-coil-containing protein kinase I
Other designations: 40S ribosomal protein S29
stearoyl-CoA desaturase (delta-9-desaturase)
Other designations: acyl-CoA desaturase|delta(9)-desaturase|delta-9 desaturase|delta-9-desaturase|fatty acid desaturase|predicted protein of HQ0998|stearoyl-CoA desaturase opposite strand
SCO1 cytochrome c oxidase assembly protein
Other designations: SCO cytochrome oxidase deficient homolog 1|protein SCO1 homolog, mitochondrial
Other designations: C-C motif chemokine 2|monocyte chemoattractant protein 1|monocyte chemoattractant protein-1|monocyte chemotactic and activating factor|monocyte chemotactic protein 1|monocyte secretory protein JE|small inducible cytokine A2 (monocyte chemotactic protein 1, homologous to mouse Sig-je)|small inducible cytokine subfamily A (Cys-Cys), member 2|small-inducible cytokine A2
Other designations: C-X-C motif chemokine 6|Small inducible cytokine subfamily B (Cys-X-Cys), member b|chemokine (C-X-C motif) ligand 6 (granulocyte chemotactic protein 2)|chemokine alpha 3|granulocyte chemotactic protein 2|small inducible cytokine subfamily B (Cys-X-Cys), member 6 (granulocyte chemotactic protein 2)|small-inducible cytokine B6
sel-1 suppressor of lin-12-like (C. elegans)
Other designations: Suppressor of lin 12 (sel-1), C. elegans, homolog of|protein sel-1 homolog 1|sel-1 suppressor of lin-12-like 1|suppressor of lin-12-like protein 1
Other designations: ASF-1|SR splicing factor 1|alternative-splicing factor 1|pre-mRNA-splicing factor SF2, P33 subunit|splicing factor 2|splicing factor, arginine/serine-rich 1
solute carrier family 1 (glial high affinity glutamate transporter), member 2
Other designations: excitatory amino acid transporter 2|excitotoxic amino acid transporter 2|glutamate/aspartate transporter II|sodium-dependent glutamate/aspartate transporter 2
solute carrier family 2 (facilitated glucose transporter), member 3
Other designations: GLUT-3|glucose transporter type 3, brain|solute carrier family 2, facilitated glucose transporter member 3
solute carrier family 3 (amino acid transporter heavy chain), member 1
Other designations: B(0,+)-type amino acid transport protein|SLC3A1 variant B|SLC3A1 variant C|SLC3A1 variant D|SLC3A1 variant E|SLC3A1 variant F|SLC3A1 variant G|amino acid transporter 1|neutral and basic amino acid transport protein rBAT|solute carrier family 3 (cystine, dibasic and neutral amino acid transporters), member 1|solute carrier family 3 (cystine, dibasic and neutral amino acid transporters, activator of cystine, dibasic and neutral amino acid transport), member 1|solute carrier family 3 member 1
solute carrier family 10 (sodium/bile acid cotransporter), member 1
Other designations: Na(+)/bile acid cotransporter|Na(+)/taurocholate transport protein|Na/taurocholate cotransporting polypeptide|cell growth-inhibiting gene 29 protein|growth-inhibiting protein 29|sodium/bile acid cotransporter|sodium/taurocholate cotransporter|sodium/taurocholate cotransporting polypeptide|solute carrier family 10 (sodium/bile acid cotransporter family), member 1|solute carrier family 10 member 1
Other designations: component of gems 1|gemin-1|survival motor neuron 1 protein|survival motor neuron protein|tudor domain containing 16A
Other designations: frizzled family member 11|protein Gx|seven transmembrane helix receptor|smoothened homolog|smoothened, frizzled family receptor|smoothened, seven transmembrane spanning receptor
sphingomyelin phosphodiesterase 1, acid lysosomal
Other designations: acid sphingomyelinase|sphingomyelin phosphodiesterase
sterol regulatory element binding transcription factor 1
Other designations: SREBP-1|class D basic helix-loop-helix protein 1|sterol regulatory element-binding protein 1
Other designations: SFRS protein kinase 2|SR protein kinase 2|SR-protein-specific kinase 2|serine kinase SRPK2|serine/arginine-rich protein-specific kinase 2|serine/arginine-rich splicing factor kinase 2|serine/threonine-protein kinase SRPK2
single-stranded DNA binding protein 1, mitochondrial
Other designations: PWP1-interacting protein 17|single-stranded DNA-binding protein, mitochondrial
signal sequence receptor, gamma (translocon-associated protein gamma)
Other designations: SSR gamma|SSR-gamma|TRAP-complex gamma subunit|TRAP-gamma|signal sequence receptor subunit gamma|translocon-associated protein gamma subunit|translocon-associated protein subunit gamma
signal transducer and activator of transcription 1, 91kDa
Other designations: signal transducer and activator of transcription 1-alpha/beta|signal transducer and activator of transcription-1|transcription factor ISGF-3 components p91/p84
signal transducer and activator of transcription 3 (acute-phase response factor)
Other designations: DNA-binding protein APRF|acute-phase response factor|signal transducer and activator of transcription 3
heat shock protein 70kDa family, member 13
Other designations: heat shock 70 kDa protein 13|microsomal stress 70 protein ATPase core|microsomal stress-70 protein ATPase core|stress 70 protein chaperone, microsome-associated, 60kD|stress 70 protein chaperone, microsome-associated, 60kDa|stress-70 protein chaperone microsome-associated 60 kDa protein
Other designations: liver kinase B1|polarization-related protein LKB1|renal carcinoma antigen NY-REN-19|serine/threonine-protein kinase 11|serine/threonine-protein kinase LKB1|serine/threonine-protein kinase STK11
sulfotransferase family, cytosolic, 1C, member 2
Other designations: SULT1C#1|sulfotransferase 1C1|sulfotransferase 1C2|sulfotransferase family, cytosolic, 1C, member 1
Other designations: 22 kDa actin-binding protein|SM22-alpha|smooth muscle protein 22-alpha|transgelin variant 2
TAF9 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 32kDa
Other designations: RNA polymerase II TBP-associated factor subunit G|transcription initiation factor TFIID 31 kD subunit|transcription initiation factor TFIID 31 kDa subunit|transcription initiation factor TFIID 32 kDa subunit|transcription initiation factor TFIID subunit 9
Other designations: thrombospondin-1|thrombospondin-1p180
Other designations: TIMP-1|collagenase inhibitor|erythroid potentiating activity|erythroid-potentiating activity|fibroblast collagenase inhibitor|metalloproteinase inhibitor 1|tissue inhibitor of metalloproteinases 1
Other designations: hToll|homolog of Drosophila toll
Other designations: LEM domain containing 4|TP alpha|TP beta/gamma|lamina-associated polypeptide 2|thymopoietin-related peptide isoform alpha|thymopoietin-related peptide isoforms beta/gamma
Other designations: APC1 protein|TNF, macrophage-derived|TNF, monocyte-derived|TNF-a|cachectin|tumor necrosis factor ligand superfamily member 2|tumor necrosis factor-alpha
Other designations: antigen NY-CO-13|cellular tumor antigen p53|mutant tumor protein 53|p53 tumor suppressor|phosphoprotein p53|transformation-related protein 53|tumor protein 53
heat shock protein 90kDa beta (Grp94), member 1
Other designations: 94 kDa glucose-regulated protein|endoplasmin|endothelial cell (HBMEC) glycoprotein|epididymis luminal protein 35|epididymis secretory sperm binding protein Li 125m|heat shock protein 90 kDa beta member 1|stress-inducible tumor rejection antigen gp96|tumor rejection antigen (gp96) 1|tumor rejection antigen 1
Other designations: E3 ubiquitin-protein ligase TRAF2|tumor necrosis factor type 2 receptor associated protein 3|tumor necrosis factor type 2 receptor-associated protein 3
Other designations: CD40 associated protein 1|CD40 binding protein|CD40 receptor associated factor 1|LMP1-associated protein 1
DnaJ (Hsp40) homolog, subfamily C, member 7
Other designations: TPR repeat protein 2|dnaJ homolog subfamily C member 7|tetratricopeptide repeat domain 2|tetratricopeptide repeat protein 2
twist family bHLH transcription factor 1
Other designations: B-HLH DNA binding protein|H-twist|TWIST homolog of drosophila|class A basic helix-loop-helix protein 38|craniosynostosis|twist basic helix-loop-helix transcription factor 1|twist homolog 1|twist-related protein 1
Other designations: KM-102-derived reductase-like factor|gene associated with retinoic and IFN-induced mortality 12 protein|gene associated with retinoic and interferon-induced mortality 12 protein|oxidoreductase|thioredoxin reductase 1, cytoplasmic|thioredoxin reductase GRIM-12|thioredoxin reductase TR1
Other designations: TSase|thymidylate synthase
Other designations: SUMO-1-protein ligase|SUMO-conjugating enzyme UBC9|SUMO-protein ligase|ubiquitin carrier protein 9|ubiquitin carrier protein I|ubiquitin conjugating enzyme 9|ubiquitin-conjugating enzyme E2I (UBC9 homolog, yeast)|ubiquitin-conjugating enzyme E2I (homologous to yeast UBC9)|ubiquitin-conjugating enzyme UbcE2A|ubiquitin-like protein SUMO-1 conjugating enzyme|ubiquitin-protein ligase E2I|ubiquitin-protein ligase I
uncoupling protein 3 (mitochondrial, proton carrier)
Other designations: mitochondrial uncoupling protein 3|solute carrier family 25 member 9
UDP-glucose ceramide glucosyltransferase
Other designations: GLCT-1|UDP-glucose:N-acylsphingosine D-glucosyltransferase|ceramide glucosyltransferase|glucosylceramide synthase
UDP glucuronosyltransferase 2 family, polypeptide B7
Other designations: 3,4-catechol estrogen specific|3,4-catechol estrogen-specific UDPGT|UDP glucuronosyltransferase 2B7|UDP-glucuronosyltransferase 2B7|UDP-glucuronosyltransferase 2B9|UDP-glucuronyltransferase, family 2, beta-7|UDPGT 2B7|UDPGTh-2
nuclear receptor subfamily 1, group H, member 2
Other designations: LX receptor beta|liver X nuclear receptor beta|nuclear orphan receptor LXR-beta|nuclear receptor NER|oxysterols receptor LXR-beta|steroid hormone-nuclear receptor NER|ubiquitously-expressed nuclear receptor
upstream transcription factor 2, c-fos interacting
Other designations: FOS-interacting protein|c-fos interacting protein|class B basic helix-loop-helix protein 12|major late transcription factor 2|upstream stimulatory factor 2
vav 2 guanine nucleotide exchange factor
Other designations: guanine nucleotide exchange factor VAV2|vav 2 oncogene
Other designations: Williams-Beuren syndrome chromosome region 1
Other designations: X-box-binding protein 1|tax-responsive element-binding protein 5
low density lipoprotein receptor-related protein 8, apolipoprotein e receptor
Other designations: ApoE receptor 2|low-density lipoprotein receptor-related protein 8
Other designations: B-cell translocation gene 2|NGF-inducible anti-proliferative protein PC3|nerve growth factor-inducible anti-proliferative|pheochromacytoma cell-3|protein BTG2
mesencephalic astrocyte-derived neurotrophic factor
Other designations: arginine-rich, mutated in early stage tumors
aminoacyl tRNA synthetase complex-interacting multifunctional protein 2
Other designations: ARS-interacting multi-functional protein 2|aminoacyl tRNA synthase complex-interacting multifunctional protein 2|multisynthase complex auxiliary component p38|multisynthetase complex auxiliary component p38|protein JTV-1
Other designations: 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestanoyl-CoA 24-hydroxylase|3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestanoyl-CoA oxidase|THCA-CoA oxidase|acyl-Coenzyme A oxidase 2, branched chain|peroxisomal acyl-coenzyme A oxidase 2|peroxisomal branched chain acyl-CoA oxidase|trihydroxycoprostanoyl-CoA oxidase
Other designations: BRCACox|acyl-Coenzyme A oxidase 3, pristanoyl|branched-chain acyl-CoA oxidase|peroxisomal acyl-coenzyme A oxidase 3|pristanoyl-CoA oxidase
Other designations: H2A histone family, member O|histone 2, H2aa3|histone H2A type 2-A
Other designations: H2B histone family, member A|histone 1, H2bg|histone H2B type 1-C/E/F/G/I|histone H2B.1 A|histone H2B.a
The protein encoded by this gene is an unusual orphan receptor that contains a putative ligand-binding domain but lacks a conventional DNA-binding domain. The gene product is a member of the nuclear hormone receptor family, a group of transcription factors regulated by small hydrophobic hormones, a subset of which do not have known ligands and are referred to as orphan nuclear receptors. The protein has been shown to interact with retinoid and thyroid hormone receptors, inhibiting their ligand-dependent transcriptional activation. In addition, interaction with estrogen receptors has been demonstrated, leading to inhibition of function. Studies suggest that the protein represses nuclear hormone receptor-mediated transactivation via two separate steps: competition with coactivators and the direct effects of its transcriptional repressor function. [provided by RefSeq, Jul 2008]
nuclear receptor subfamily 0, group B, member 2
inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma
Other designations: I-kappa-B kinase subunit gamma|IKKAP1|IKKG|IkB kinase gamma subunit|NF-kappa-B essential modifier|NF-kappa-B essential modulator|NFkappaB essential modulator|ikB kinase subunit gamma|ikB kinase-associated protein 1|incontinentia pigmenti|inhibitor of nuclear factor kappa-B kinase subunit gamma
cytochrome P450, family 4, subfamily F, polypeptide 2
Other designations: CYPIVF2|cytochrome P450 4F2|cytochrome P450, subfamily IVF, polypeptide 2|cytochrome P450-LTB-omega|leukotriene B4 omega-hydroxylase|leukotriene-B(4) 20-monooxygenase 1|leukotriene-B(4) omega-hydroxylase 1|leukotriene-B4 20-monooxygenase
Other designations: pirin|probable quercetin 2,3-dioxygenase PIR|probable quercetinase
protein kinase, interferon-inducible double stranded RNA dependent activator
Other designations: PKR-associated protein X|PKR-associating protein X|interferon-inducible double stranded RNA-dependent protein kinase activator A|interferon-inducible double-stranded RNA-dependent protein kinase activator A|protein activator of the interferon-induced protein kinase|protein kinase, interferon-inducible double stranded RNA-dependent activator|protein kinase, interferon-inducible double-stranded RNA-dependent activator
eukaryotic translation initiation factor 4E binding protein 3
Other designations: eIF4E-binding protein 3|eukaryotic initiation factor 4E-binding protein 3|eukaryotic translation initiation factor 4E-binding protein 3
ATP-binding cassette, sub-family B (MDR/TAP), member 11
Other designations: ABC member 16, MDR/TAP subfamily|ATP-binding cassette sub-family B member 11|bile salt export pump|progressive familial intrahepatic cholestasis 2|sister p-glycoprotein
eukaryotic translation initiation factor 3, subunit A
Other designations: EIF3, p180 subunit|centrosomin homolog|cytoplasmic protein p167|eIF-3-theta|eIF3 p167|eIF3 p180|eIF3 p185|eukaryotic translation initiation factor 3 subunit 10|eukaryotic translation initiation factor 3 subunit A|eukaryotic translation initiation factor 3, subunit 10 (theta, 150/170kD)|eukaryotic translation initiation factor 3, subunit 10 (theta, 170kD)|eukaryotic translation initiation factor 3, subunit 10 theta, 150/170kDa|eukaryotic translation initiation factor 3, subunit 10, 170kD
eukaryotic translation initiation factor 3, subunit B
Other designations: eIF-3-eta|eIF3 p110|eIF3 p116|eukaryotic translation initiation factor 3 subunit 9|eukaryotic translation initiation factor 3 subunit B|eukaryotic translation initiation factor 3, subunit 9 (eta, 116kD)|eukaryotic translation initiation factor 3, subunit 9 eta, 116kDa|hPrt1|prt1 homolog
eukaryotic translation initiation factor 3, subunit C
Other designations: cell migration-inducing protein 17|eIF3 p110|eukaryotic translation initiation factor 3 subunit 8|eukaryotic translation initiation factor 3 subunit C|eukaryotic translation initiation factor 3, subunit 8 (110kD)|eukaryotic translation initiation factor 3, subunit 8, 110kDa
eukaryotic translation initiation factor 3, subunit D
Other designations: eIF-3-zeta|eIF3 p66|eukaryotic translation initiation factor 3 subunit 7|eukaryotic translation initiation factor 3 subunit D|eukaryotic translation initiation factor 3, subunit 7 zeta, 66/67kDa|translation initiation factor eIF3 p66 subunit
eukaryotic translation initiation factor 3, subunit F
Other designations: deubiquitinating enzyme eIF3f|eIF-3-epsilon|eIF3-epsilon|eukaryotic translation initiation factor 3 subunit F|eukaryotic translation initiation factor 3, subunit 5 (epsilon, 47kD)|eukaryotic translation initiation factor 3, subunit 5 epsilon, 47kDa
eukaryotic translation initiation factor 3, subunit G
Other designations: eIF-3 RNA-binding subunit|eIF-3-delta|eIF3 p42|eIF3 p44|eukaryotic translation initiation factor 3 RNA-binding subunit|eukaryotic translation initiation factor 3 subunit 4|eukaryotic translation initiation factor 3 subunit G|eukaryotic translation initiation factor 3 subunit p42|eukaryotic translation initiation factor 3, subunit 4 (delta, 44kD)|eukaryotic translation initiation factor 3, subunit 4 delta, 44kDa
eukaryotic translation initiation factor 3, subunit H
Other designations: eIF-3-gamma|eIF3 p40 subunit|eukaryotic translation initiation factor 3 subunit 3|eukaryotic translation initiation factor 3 subunit H|eukaryotic translation initiation factor 3, subunit 2 (beta, 36kD)|eukaryotic translation initiation factor 3, subunit 3 (gamma, 40kD)|eukaryotic translation initiation factor 3, subunit 3 gamma, 40kDa
eukaryotic translation initiation factor 3, subunit I
Other designations: TGF-beta receptor-interacting protein 1|TGFbeta receptor-interacting protein 1|eIF-3-beta|eIF3 p36|eukaryotic translation initiation factor 3 subunit 2|eukaryotic translation initiation factor 3 subunit I|eukaryotic translation initiation factor 3, subunit 2 (beta, 36kD)|eukaryotic translation initiation factor 3, subunit 2 beta, 36kDa|predicted protein of HQ2242
eukaryotic translation initiation factor 3, subunit J
Other designations: eukaryotic translation initiation factor 3 subunit J|eukaryotic translation initiation factor 3, subunit 1 (alpha, 35kD)
eukaryotic translation initiation factor 4 gamma, 3
Other designations: eIF-4-gamma 3|eIF-4-gamma II|eukaryotic translation initiation factor 4 gamma 3
Other designations: TNFR1-associated death domain protein|tumor necrosis factor receptor type 1 associated death domain protein|tumor necrosis factor receptor type 1-associated DEATH domain protein|tumor necrosis factor receptor-1-associated protein
tumor necrosis factor (ligand) superfamily, member 10
Other designations: Apo-2 ligand|TNF-related apoptosis inducing ligand TRAIL|chemokine tumor necrosis factor ligand superfamily member 10|tumor necrosis factor (ligand) family, member 10|tumor necrosis factor apoptosis-inducing ligand splice variant delta|tumor necrosis factor ligand superfamily member 10
Other designations: 28 kDa peroxisomal integral membrane protein|peroxin-11A|peroxisomal biogenesis factor 11A|peroxisomal membrane protein 11A|protein PEX11 homolog alpha
Other designations: FADD-like anti-apoptotic molecule|FADD-like antiapoptotic molecule 1|MACH-related inducer of toxicity|caspase homolog|caspase-eight-related protein|caspase-like apoptosis regulatory protein|caspase-related inducer of apoptosis|cellular FLICE-like inhibitory protein|inhibitor of FLICE|usurpin beta
cyclin-dependent kinase 5, regulatory subunit 1 (p35)
Other designations: CDK5 activator 1|TPKII regulatory subunit|cyclin-dependent kinase 5 activator 1|cyclin-dependent kinase 5 regulatory subunit 1|neuronal CDK5 activator|regulatory partner for CDK5 kinase|tau protein kinase II 23kDa subunit
nuclear receptor subfamily 1 group I member 2
Other designations: PACAP-responsive gene 1 protein|anti-death protein|differentiation-dependent gene 2 protein|expressed in pancreatic carcinoma|gly96, mouse, homolog of|immediate early protein GLY96|immediate early response 3 protein|immediately early gene X-1|protein DIF-2|radiation-inducible immediate-early gene IEX-1
Other designations: pantetheinase|pantetheine hydrolase|vanin-1|vannin 1|vascular non-inflammatory molecule 1
Other designations: SP-lyase 1|SPL 1|hSPL|sphingosine-1-phosphate aldolase
solute carrier family 5 (sodium/multivitamin and iodide cotransporter), member 6
Other designations: Na(+)-dependent multivitamin transporter|Na+-dependent multivitamin transporter|sodium-dependent multivitamin transporter|solute carrier family 5 (sodium-dependent vitamin transporter), member 6|solute carrier family 5 member 6
eukaryotic translation initiation factor 2B, subunit 4 delta, 67kDa
Other designations: eIF-2B GDP-GTP exchange factor subunit delta|eukaryotic translation initiation factor 2B subunit 4 delta|translation initiation factor eIF-2B subunit delta|translation initiation factor eIF-2b delta subunit
eukaryotic translation initiation factor 2B, subunit 3 gamma, 58kDa
Other designations: eIF-2B GDP-GTP exchange factor subunit gamma|translation initiation factor eIF-2B subunit gamma
eukaryotic translation initiation factor 2B, subunit 2 beta, 39kDa
Other designations: S20I15|S20III15|eIF-2B GDP-GTP exchange factor subunit beta|translation initiation factor eIF-2B subunit beta
eukaryotic translation initiation factor 2B, subunit 5 epsilon, 82kDa
Other designations: eIF-2B GDP-GTP exchange factor subunit epsilon|translation initiation factor eIF-2B subunit epsilon
eukaryotic translation initiation factor 2, subunit 2 beta, 38kDa
Other designations: eukaryotic translation initiation factor 2 subunit 2|eukaryotic translation initiation factor 2 subunit beta|protein phosphatase 1, regulatory subunit 67
Other designations: Fyn-associated phosphoprotein SKAP55 homologue|Pyk2/RAFTK-associated protein|SKAP-55HOM|SKAP55 homolog|retinoic acid-induced protein 70|src family associated phosphoprotein 2|src family-associated phosphoprotein 2|src kinase-associated phosphoprotein 2|src kinase-associated phosphoprotein 55-related protein|src kinase-associated phosphoprotein of 55-related protein|src-associated adapter protein with PH and SH3 domains|src-associated adaptor protein
Other designations: ANG-3|angioarrestin|angiopoietin 3|angiopoietin Y1|angiopoietin-3|angiopoietin-like protein 1|angiopoietin-related protein 1|dJ595C2.2 (angiopoietin Y1)
eukaryotic translation initiation factor 1A, Y-linked
Other designations: eIF-1A Y isoform|eukaryotic translation initiation factor 1A, Y chromosome|eukaryotic translation initiation factor 1A, Y-chromosomal|eukaryotic translation initiation factor 4C
Other designations: G2/mitotic-specific cyclin-B2
Other designations: cellugyrin|synaptogyrin-2
proprotein convertase subtilisin/kexin type 7
Other designations: lymphoma proprotein convertase|prohormone convertase 7|prohormone convertase PC7|proprotein convertase 7|proprotein convertase 8|proprotein convertase PC7|subtilisin/kexin-like protease PC7
mitogen-activated protein kinase kinase kinase 13
Other designations: leucine zipper-bearing kinase|mixed lineage kinase
Other designations: DEAD (Asp-Glu-Ala-Asp) box polypeptide 21|DEAD box protein 21|DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 21|Gu protein|RH II/Gu|RNA helicase II/Gu alpha|gu-alpha|nucleolar RNA helicase 2|nucleolar RNA helicase Gu|nucleolar RNA helicase II
nucleolar and coiled-body phosphoprotein 1
Other designations: 140 kDa nucleolar phosphoprotein|HCV NS5A trans-regulated protein 13|HCV NS5A-transactivated protein 13|hepatitis C virus NS5A-transactivated protein 13|nucleolar 130 kDa protein|nucleolar and coiled-body phosphprotein 1|nucleolar phosphoprotein p130|nucleolar protein p130
Other designations: ATP-dependent DNA helicase Q5|DNA helicase, RecQ-like type 5
Other designations: delta(6) desaturase|delta(6) fatty acid desaturase|delta-6 desaturase|delta-6 fatty acid desaturase|delta-6-desaturase|linoleoyl-CoA desaturase (delta-6-desaturase)-like 2
cytochrome P450, family 7, subfamily B, polypeptide 1
Other designations: 25-hydroxycholesterol 7-alpha-hydroxylase|cytochrome P450 7B1|cytochrome P450, subfamily VIIB (oxysterol 7 alpha-hydroxylase), polypeptide 1|oxysterol 7-alpha-hydroxylase|oxysterol 7alpha-hydroxylase
Other designations: 130 kDa transcriptional co-activator|133 kDa transcriptional co-activator|activator-recruited cofactor 130 kDa component|cofactor required for Sp1 transcriptional activation subunit 3|mediator of RNA polymerase II transcription subunit 23|vitamin D3 receptor interacting protein
eukaryotic translation initiation factor 2-alpha kinase 3
Other designations: PRKR-like endoplasmic reticulum kinase|eukaryotic translation initiation factor 2 alpha kinase 3|hsPEK|pancreatic EIF2-alpha kinase
eukaryotic translation initiation factor 4E family member 2
Other designations: eIF-4E type 2|eIF4E-like cap-binding protein|eIF4E-like protein 4E-LP|eukaryotic translation initiation factor 4E homologous protein|eukaryotic translation initiation factor 4E type 2|eukaryotic translation initiation factor 4E-like 3|mRNA cap-binding protein type 3
serine palmitoyltransferase, long chain base subunit 2
Other designations: LCB 2|SPT 2|long chain base biosynthesis protein 2a|serine palmitoyltransferase 2|serine palmitoyltransferase, subunit II|serine-palmitoyl-CoA transferase 2
Other designations: NRG-1|NSAID (nonsteroidal anti-inflammatory drug)-activated protein 1|NSAID-activated gene 1 protein|NSAID-regulated gene 1 protein|PTGF-beta|growth/differentiation factor 15|macrophage inhibitory cytokine 1|placental TGF-beta|placental bone morphogenetic protein|prostate differentiation factor
inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon
Other designations: I-kappa-B kinase epsilon|IKK-epsilon|IKK-related kinase epsilon|inducible I kappa-B kinase|inducible IkappaB kinase|inhibitor of nuclear factor kappa-B kinase subunit epsilon
GRIP and coiled-coil domain containing 2
Other designations: 185 kDa Golgi coiled-coil protein|CLL-associated antigen KW-11|CTCL tumor antigen se1-1|GCC protein, 185-kD|GRIP and coiled-coil domain-containing protein 2|Golgi coiled-coil protein GCC185|Ran-binding protein 2-like 4|renal carcinoma antigen NY-REN-53
eukaryotic translation initiation factor 5B
Other designations: eIF-5B|translation initiation factor IF-2|translation initiation factor IF2
ER degradation enhancer, mannosidase alpha-like 1
Other designations: ER degradation-enhancing alpha-mannosidase-like 1|ER degradation-enhancing alpha-mannosidase-like protein 1
homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1
Other designations: MMS-inducible|homocysteine-inducible endoplasmic reticulum stress-inducible ubiquitin-like domain member 1 protein|homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein|methyl methanesulfonate (MMF)-inducible fragment protein 1
Other designations: HCV NS5A-transactivated protein 9|PCNA-associated factor|PCNA-associated factor of 15 kDa|hepatitis C virus NS5A-transactivated protein 9|overexpressed in anaplastic thyroid carcinoma 1
eukaryotic translation initiation factor 4A3
Other designations: ATP-dependent RNA helicase DDX48|ATP-dependent RNA helicase eIF4A-3|DEAD (Asp-Glu-Ala-Asp) box polypeptide 48|DEAD box protein 48|NMP 265|eIF-4A-III|eIF4A-III|eukaryotic initiation factor 4A-III|eukaryotic initiation factor 4A-like NUK-34|eukaryotic translation initiation factor 4A|hNMP 265|nuclear matrix protein 265
translocase of outer mitochondrial membrane 20 homolog (yeast)
Other designations: mitochondrial 20 kDa outer membrane protein|mitochondrial import receptor subunit TOM20 homolog|outer mitochondrial membrane receptor Tom20|translocase of outer mitochondrial membrane 20 homolog type II
DnaJ (Hsp40) homolog, subfamily C, member 6
Other designations: DnaJ (Hsp40) homolog, subfamily B, member 6|auxilin|putative tyrosine-protein phosphatase auxilin
Other designations: SEC24 family, member D|SEC24 related gene family, member D|SEC24-related protein D|protein transport protein Sec24D
Other designations: AMP-activated protein kinase family member 5|AMPK-related protein kinase 5|NUAK family SNF1-like kinase 1|omphalocele kinase 1
lysophosphatidylglycerol acyltransferase 1
Other designations: acyl-CoA:lysophosphatidylglycerol acyltransferase 1|family with sequence similarity 34, member A
Other designations: BOV-1|RNA binding motif protein 8B|RNA-binding motif protein 8A|RNA-binding protein 8A|RNA-binding protein Y14|binder of OVCA1-1|ribonucleoprotein RBM8|ribonucleoprotein RBM8A
This gene encodes a member of the nuclear receptor superfamily, and is a key regulator of xenobiotic and endobiotic metabolism. The protein binds to DNA as a monomer or a heterodimer with the retinoid X receptor and regulates the transcription of target genes involved in drug metabolism and bilirubin clearance, such as cytochrome P450 family members. Unlike most nuclear receptors, this transcriptional regulator is constitutively active in the absence of ligand but is regulated by both agonists and inverse agonists. Ligand binding results in translocation of this protein to the nucleus, where it activates or represses target gene transcription. These ligands include bilirubin, a variety of foreign compounds, steroid hormones, and prescription drugs. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Constitutive Activator Of Retinoid Response
Nuclear Receptor Subfamily 1 Group I Member 3
nuclear receptor subfamily 1, group H, member 4
retinoid X receptor-interacting protein 14
Other designations: 153 kDa nucleoporin|nuclear pore complex protein Nup153|nuclear pore complex protein hnup153|nucleoporin Nup153
Other designations: CASP8 associated protein 2|CASP8-associated protein 2|FLASH homolog RIP25|FLICE associated huge|FLICE-associated huge protein|human FLASH
Other designations: HIV-Nef associated acyl-CoA thioesterase|acyl-coenzyme A thioesterase 8|choloyl-CoA hydrolase|choloyl-coenzyme A thioesterase|long-chain fatty-acyl-CoA hydrolase|palmitoyl-CoA hydrolase|peroxisomal acyl-CoA thioesterase 1|peroxisomal acyl-coenzyme A thioester hydrolase 1|peroxisomal long-chain acyl-CoA thioesterase 1|thioesterase II|thioesterase III
Other designations: bcl-2 interacting mediator of cell death|bcl-2 interacting protein Bim|bcl-2-like protein 11|bcl-2-related ovarian death agonist
glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase
Other designations: N-acylmannosamine kinase|UDP-GlcNAc-2-epimerase/ManAc kinase|UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase|UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase|bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
DnaJ (Hsp40) homolog, subfamily B, member 6
Other designations: DnaJ-like 2 protein|dnaJ homolog subfamily B member 6|heat shock protein J2|limb girdle muscular dystrophy 1D (autosomal dominant)
adaptor-related protein complex 1, mu 2 subunit
Other designations: AP-1 complex subunit mu-2|AP-mu chain family member mu1B|HA1 47 kDa subunit 2|adaptor protein complex AP-1 mu-2 subunit|adaptor protein complex AP-1 subunit mu-2|adaptor-related protein complex 1 mu-2 subunit|adaptor-related protein complex 1 subunit mu-2|clathrin assembly protein complex 1 medium chain 2|clathrin assembly protein complex 1 mu-2 medium chain 2|clathrin coat assembly protein AP47 2|clathrin coat associated protein AP47 2|clathrin-associated adaptor medium chain mu2|golgi adaptor AP-1 47 kDa protein|golgi adaptor HA1/AP1 adaptin mu-2 subunit|mu-adaptin 2|mu1B-adaptin
RAS guanyl releasing protein 1 (calcium and DAG-regulated)
Other designations: RAS guanyl nucleotide-releasing protein 1|RAS guanyl-releasing protein 1|calcium and DAG-regulated guanine nucleotide exchange factor II|guanine nucleotide exchange factor, calcium- and DAG-regulated, Rap1A|ras activator RasGRP
eukaryotic translation initiation factor 1
Other designations: protein translation factor SUI1 homolog|sui1iso1
Other designations: angiopoietin-like factor (CDT6)|angiopoietin-like protein 7|angiopoietin-related protein 7|cornea-derived transcript 6 protein
STIP1 homology and U-box containing protein 1, E3 ubiquitin protein ligase
Other designations: CLL-associated antigen KW-8|E3 ubiquitin-protein ligase CHIP|STIP1 homology and U box-containing protein 1|antigen NY-CO-7|carboxy terminus of Hsp70-interacting protein|heat shock protein A binding protein 2 (c-terminal)|serologically defined colon cancer antigen 7
eukaryotic translation initiation factor 1B
Other designations: eukaryotic translation initiation factor 1b|protein translation factor SUI1 homolog GC20|translation factor sui1 homolog
Other designations: dystonia 4, torsion (autosomal dominant)|tubulin beta-4 chain|tubulin beta-4A chain|tubulin, beta, 5
Other designations: E3 SUMO-protein ligase PIAS3|protein inhibitor of activated STAT protein 3|zinc finger, MIZ-type containing 5
Other designations: Ser-Met dipeptidase|aminopeptidase|blood plasma glutamate carboxypeptidase|lysosomal dipeptidase
Other designations: differentially expressed in cancerous and non-cancerous lung cells 1|spondin-2
Other designations: 72 kDa ICln-binding protein|HMT1 hnRNP methyltransferase-like 5|SKB1 homolog|histone-arginine N-methyltransferase PRMT5|jak-binding protein 1|protein arginine N-methyltransferase 5|shk1 kinase-binding protein 1 homolog
eukaryotic translation initiation factor 3, subunit M
Other designations: B5 receptor|PCI domain containing 1 (herpesvirus entry mediator)|PCI domain-containing protein 1|dendritic cell protein|eukaryotic translation initiation factor 3 subunit M|fetal lung protein B5|transport and golgi organization 7 homolog
Other designations: 150 kDa oxygen-regulated protein|170 kDa glucose-regulated protein|hypoxia up-regulated protein 1|oxygen regulated protein (150kD)
Other designations: PKC-interacting cousin of thioredoxin|PKC-theta-interacting protein|PKCq-interacting protein|glutaredoxin 4|glutaredoxin-3|thioredoxin-like protein 2
late endosomal/lysosomal adaptor, MAPK and MTOR activator 5
Other designations: HBV X-interacting protein|HBx-interacting protein|hepatitis B virus x interacting protein|hepatitis B virus x-interacting protein (9.6kD)|late endosomal/lysosomal adaptor and MAPK and MTOR activator 5|ragulator complex protein LAMTOR5
Other designations: 30 kDa HIV-1 TAT-interacting protein|HIV-1 TAT-interactive protein 2|Tat-interacting protein (30kD)|oxidoreductase HTATIP2|short chain dehydrogenase/reductase family 44U, member 1
Other designations: Fas-ligand associated factor 2|SH3 domain protein 5|c-Cbl associated protein|ponsin|sorbin and SH3 domain-containing protein 1
Other designations: protein mab-21-like 2
Other designations: PDZ and LIM domain protein 5|enigma homolog|enigma-like LIM domain protein|enigma-like PDZ and LIM domains protein
Other designations: RAD51-associated protein 1|RAD51-interacting protein
Other designations: adenovirus E3 14.7 kDa-interacting protein 1|adenovirus E3-14.7K interacting protein 1|rag A|ras-related GTP-binding protein A
Other designations: B5T overexpressed gene protein|B5T-overexpressed gene protein|RBBP-10|RBBP-9|putative hydrolase RBBP9|retinoblastoma-binding protein 10|retinoblastoma-binding protein 9|retinoma-binding protein 9
Other designations: PLK-2|serine/threonine-protein kinase PLK2|serine/threonine-protein kinase SNK|serum-inducible kinase
Other designations: C-C chemokine receptor type 9|G protein-coupled receptor 28
progesterone receptor membrane component 1
Other designations: membrane-associated progesterone receptor component 1|progesterone binding protein
cytochrome P450, family 46, subfamily A, polypeptide 1
Other designations: CH24H|cholesterol 24-hydroxylase|cytochrome P450 46A1|cytochrome P450, subfamily 46 (cholesterol 24-hydroxylase)
Other designations: activated RNA polymerase II transcription cofactor 4|activated RNA polymerase II transcriptional coactivator p15|positive cofactor 4
sphingomyelin phosphodiesterase, acid-like 3A
Other designations: 0610010C24Rik|ASM-like phosphodiesterase 3a|acid sphingomyelinase-like phosphodiesterase 3a
Other designations: DBF4 homolog|DBF4 zinc finger A|DBF4-type zinc finger-containing protein 1|activator of S phase kinase|chiffon homolog A|protein DBF4 homolog A|zinc finger, DBF-type containing 1
Other designations: Sec61 complex, beta subunit|protein translocation complex beta|protein transport protein SEC61 beta subunit|protein transport protein Sec61 subunit beta
Other designations: acyl-coenzyme A thioester hydrolase 2a|acyl-coenzyme A thioesterase 2, mitochondrial|long-chain acyl-CoA thioesterase 2|mitochondrial acyl-CoA thioesterase 1|peroxisomal long-chain acyl-coA thioesterase 2
Other designations: GLI pathogenesis-related 1 (glioma)|gliPR 1|glioma pathogenesis-related protein 1|protein RTVP-1|related to testis-specific, vespid, and pathogenesis proteins 1|testes-specific vespid and pathogenesis protein 1
KDEL (Lys-Asp-Glu-Leu) endoplasmic reticulum protein retention receptor 2
Other designations: (Lys-Asp-Glu-Leu) endoplasmic reticulum protein retention receptor 2|ER lumen protein retaining receptor 2|ERD-2-like protein|ERD2-like protein 1|KDEL endoplasmic reticulum protein retention receptor 2|KDEL receptor 2
Other designations: cyclic AMP-dependent transcription factor ATF-7|transcription factor ATF-A
DnaJ (Hsp40) homolog, subfamily B, member 4
Other designations: DnaJ-like heat shock protein 40|HSP40 homolog|dnaJ homolog subfamily B member 4|heat shock 40 kDa protein 1 homolog|heat shock protein 40 homolog|human liver DnaJ-like protein
Other designations: FAS-associated factor 1|TNFRSF6-associated factor 1|UBX domain protein 3A|UBX domain-containing protein 12|UBX domain-containing protein 3A
Other designations: Ca-independent phospholipase A1/2|H-rev 107 protein homolog|HRAS-like suppressor 1|HRAS-like suppressor 3|adipose-specific PLA2|adipose-specific phospholipase A2|group XVI phospholipase A1/A2|group XVI phospholipase A2|renal carcinoma antigen NY-REN-65
nudix (nucleoside diphosphate linked moiety X)-type motif 4
Other designations: DIPP-2|diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase 2|diphosphoinositol polyphosphate phosphohydrolase 2|diphosphoinositol polyphosphate phosphohydrolase type 2
nudix (nucleoside diphosphate linked moiety X)-type motif 5
Other designations: 8-oxo-dGDP phosphatase|ADP-sugar pyrophosphatase
cytochrome P450, family 4, subfamily F, polypeptide 8
Other designations: cytochrome P450 4F8|cytochrome P450, subfamily IVF, polypeptide 8|flavoprotein-linked monooxygenase|microsomal monooxygenase
Other designations: CTE-IIa|acyl-CoA thioesterase 2|acyl-CoA thioesterase, long chain|brain acyl CoA hydrolase|brain acyl-CoA hydrolase|cytosolic acyl coenzyme A thioester hydrolase|long chain acyl-CoA thioester hydrolase
Other designations: lysophospholipase homolog|monoacylglycerol lipase
Other designations: cAMP-dependent transcription factor ATF-5|cyclic AMP-dependent transcription factor ATF-5|transcription factor ATFx
DnaJ (Hsp40) homolog, subfamily C, member 8
Other designations: dnaJ homolog subfamily C member 8|splicing protein spf31
protein phosphatase, Mg2+/Mn2+ dependent, 1E
Other designations: ca(2+)/calmodulin-dependent protein kinase phosphatase N|caMKP-nucleus|nuclear calmodulin-dependent protein kinase phosphatase|partner of PIX 1|partner of PIX-alpha|partner of PIXA|protein phosphatase 1E|protein phosphatase 1E (PP2C domain containing)
Other designations: NACHT, LRR and PYD containing protein 1|NACHT, LRR and PYD domains-containing protein 1|NACHT, leucine rich repeat and PYD (pyrin domain) containing 1|NACHT, leucine rich repeat and PYD containing 1|caspase recruitment domain protein 7|caspase recruitment domain-containing protein 7|death effector filament-forming Ced-4-like apoptosis protein|nucleotide-binding domain and caspase recruitment domain|nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 1
Other designations: cAMP-dependent transcription factor ATF-6 alpha|cyclic AMP-dependent transcription factor ATF-6 alpha
aldo-keto reductase family 7, member A3 (aflatoxin aldehyde reductase)
Other designations: AFB1 aldehyde reductase 2|AFB1-AR 2|aflatoxin B1 aldehyde reductase 2|aflatoxin B1 aldehyde reductase member 3
Other designations: TPR repeat protein 39A|differentially expressed in MCF7 with estradiol protein 6|tetratricopeptide repeat protein 39A
Other designations: bifunctional arginine demethylase and lysyl-hydroxylase JMJD6|histone arginine demethylase JMJD6|jmjC domain-containing protein 6|jumonji domain-containing protein 6|lysyl-hydroxylase JMJD6|peptide-lysine 5-dioxygenase JMJD6|phosphatidylserine receptor
DnaJ (Hsp40) homolog, subfamily C, member 9
Other designations: DnaJ protein SB73|dnaJ homolog subfamily C member 9
DnaJ (Hsp40) homolog, subfamily C, member 13
Other designations: DnaJ domain-containing protein RME-8|RME-8|dnaJ homolog subfamily C member 13|required for receptor-mediated endocytosis 8
DnaJ (Hsp40) homolog, subfamily C, member 16
Other designations: dnaJ homolog subfamily C member 16|novel DnaJ domain-containing protein
Other designations: angiopoietin-like protein 2|angiopoietin-related protein 2
Other designations: QAPRTase|epididymis secretory sperm binding protein Li 90n|nicotinate-nucleotide pyrophosphorylase (carboxylating)|nicotinate-nucleotide pyrophosphorylase [carboxylating]
caspase 14, apoptosis-related cysteine peptidase
Other designations: CASP-14|apoptosis-related cysteine protease|caspase 14, apoptosis-related cysteine protease|caspase-14
Other designations: origin recognition complex subunit 6
Other designations: acyl-CoA thioester hydrolase 9|acyl-Coenzyme A thioesterase 2, mitochondrial|acyl-coenzyme A thioesterase 9, mitochondrial|mitochondrial Acyl-CoA Thioesterase
protein phosphatase 1, regulatory subunit 15A
Other designations: growth arrest and DNA damage-inducible protein GADD34|growth arrest and DNA-damage-inducible 34|myeloid differentiation primary response protein MyD116 homolog|protein phosphatase 1 regulatory subunit 15A|protein phosphatase 1, regulatory (inhibitor) subunit 15A
Other designations: 1-O-acylceramide synthase|LCAT-like lysophospholipase|group XV phospholipase A2|lysophospholipase 3 (lysosomal phospholipase A2)|lysosomal phospholipase A2
Other designations: OTTHUMT00000075032|PWP1-interacting protein 8|SDF2-like 1|SDF2-like protein 1|dihydropyrimidinase-like 2|stromal cell-derived factor 2-like protein 1
GABA(A) receptors associated protein like 3, pseudogene
DnaJ (Hsp40) homolog, subfamily B, member 5
Other designations: dnaJ homolog subfamily B member 5|heat shock cognate 40|heat shock protein Hsp40-2|heat shock protein Hsp40-3|heat shock protein cognate 40
Other designations: POU domain transcription factor OCT11a|POU domain, class 2, transcription factor 3|octamer-binding protein 11|octamer-binding transcription factor 11|transcription factor PLA-1|transcription factor Skn-1
tsukushi, small leucine rich proteoglycan
Other designations: E2-induced gene 4 protein|leucine rich repeat containing 54|leucine-rich repeat-containing protein 54|tsukushi homolog|tsukushi small leucine rich proteoglycan homolog|tsukushin
Other designations: START domain containing 14|StAR-related lipid transfer (START) domain containing 14|acyl-CoA thioester hydrolase 11|acyl-coenzyme A thioesterase 11|adipose-associated thioesterase|brown fat-inducible thioesterase|thioesterase superfamily member 1|thioesterase, adipose associated
Other designations: 1600020H07Rik|2-hydroxyphytanol-CoA lyase|2-hydroxyphytanoyl-CoA lyase|phytanoyl-CoA 2-hydroxylase 2|phytanoyl-CoA hydroxylase 2
ADP-ribosylation factor GTPase activating protein 3
Other designations: ADP-ribosylation factor GTPase activating protein 1|ADP-ribosylation factor GTPase-activating protein 3|ARF GAP 3
Other designations: DEAD box protein|DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 26|RNA helicase HDB|protein deleted in cancer 1
cysteine and histidine-rich domain (CHORD) containing 1
Other designations: CHORD-containing protein 1|CHP-1|chord domain-containing protein 1|cysteine and histidine-rich domain (CHORD)-containing 1|cysteine and histidine-rich domain (CHORD)-containing, zinc-binding protein 1|cysteine and histidine-rich domain-containing protein 1|protein morgana
DnaJ (Hsp40) homolog, subfamily C, member 2
Other designations: M-phase phosphoprotein 11|dnaJ homolog subfamily C member 2|zuotin related factor 1|zuotin-related factor 1
eukaryotic translation initiation factor 2-alpha kinase 1
Other designations: heme regulated initiation factor 2 alpha kinase|heme sensitive initiation factor 2a kinase|heme-controlled repressor|heme-regulated eukaryotic initiation factor eIF-2-alpha kinase|heme-regulated inhibitor|heme-regulated initiation factor 2-alpha kinase|heme-regulated repressor|hemin-sensitive initiation factor 2-alpha kinase
Other designations: PTH-responsive osteosarcoma B1 protein|bardet-Biedl syndrome 9 protein|parathyroid hormone-responsive B1 gene protein|protein PTHB1
tumor necrosis factor receptor superfamily, member 21
Other designations: TNFR-related death receptor 6|death receptor 6|tumor necrosis factor receptor superfamily member 21
Other designations: p53 activated gene 26|p53 regulated PA26 nuclear protein|sestrin-1
sushi-repeat containing protein, X-linked 2
Other designations: sushi repeat-containing protein SRPX2|sushi-repeat protein up-regulated in leukemia|sushi-repeat protein upregulated in leukemia|sushi-repeat-containing protein, X-linked 2
Other designations: angiopoietin 5|angiopoietin-related protein 3
eukaryotic translation initiation factor 3, subunit K
Other designations: eIF-3 p25|eIF-3 p28|eukaryotic translation initiation factor 3 subunit 12|eukaryotic translation initiation factor 3 subunit K|eukaryotic translation initiation factor 3, subunit 12|muscle specific|muscle-specific gene M9 protein
Other designations: AAA nuclear coregulator cancer-associated protein|ATPase family AAA domain-containing protein 2
NADH dehydrogenase (ubiquinone) complex I, assembly factor 4
Other designations: NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, assembly factor 4|NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 4|hormone-regulated proliferation-associated protein of 20 kDa|hormone-regulated proliferation-associated protein, 20 kDa
ubiquitin-conjugating enzyme E2T (putative)
Other designations: HSPC150 protein similar to ubiquitin-conjugating enzyme|cell proliferation-inducing gene 50 protein|ubiquitin carrier protein T|ubiquitin conjugating enzyme|ubiquitin-conjugating enzyme E2 T|ubiquitin-protein ligase T
DnaJ (Hsp40) homolog, subfamily C, member 15
Other designations: DNAJ domain-containing|DnaJ (Hsp40) homolog, subfamily D, member 1|cell growth-inhibiting gene 22 protein|dnaJ homolog subfamily C member 15|methylation-controlled J protein
Other designations: ATP-dependent RNA helicase DDX25|DEAD (Asp-Glu-Ala-Asp) box polypeptide 25|DEAD box protein 25|DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 25|gonadotropin-regulated testicular RNA helicase
ubiquitin-like with PHD and ring finger domains 1
Other designations: E3 ubiquitin-protein ligase UHRF1|RING finger protein 106|inverted CCAAT box-binding protein of 90 kDa|nuclear phosphoprotein 95|nuclear protein 95|nuclear zinc finger protein Np95|transcription factor ICBP90|ubiquitin-like PHD and RING finger domain-containing protein 1|ubiquitin-like, containing PHD and RING finger domains, 1
cytochrome P450, family 2, subfamily S, polypeptide 1
Other designations: CYPIIS1|cytochrome P450 2S1|cytochrome P450 family member predicted from ESTs|cytochrome P540, subfamily IIS, polypeptide 1
transformer 2 alpha homolog (Drosophila)
Other designations: TRA-2 alpha|TRA2-alpha|Tra2alpha|htra-2 alpha|htra-2-alpha|putative MAPK activating protein PM24|transformer-2 alpha|transformer-2 protein homolog A|transformer-2 protein homolog alpha
hypoxia inducible lipid droplet-associated
Other designations: hypoxia inducible gene 2|hypoxia-inducible gene 2 protein|hypoxia-inducible lipid droplet-associated protein|hypoxia-inducible protein 2
oxidative stress induced growth inhibitor 1
Other designations: bone marrow stromal cell-derived growth inhibitor|ovary, kidney and liver protein 38|oxidative stress-induced growth inhibitor 1|pregnancy-induced growth inhibitor OKL38
S-phase cyclin A-associated protein in the ER
Other designations: S phase cyclin A-associated protein in the ER|S phase cyclin A-associated protein in the endoplasmic reticulum|zinc finger protein 291
hepatoma-derived growth factor, related protein 3
Other designations: hepatoma-derived growth factor 2|hepatoma-derived growth factor-related protein 3
Other designations: PPARG angiopoietin related protein|angiopoietin-related protein 4|fasting-induced adipose factor|hepatic angiopoietin-related protein|hepatic fibrinogen/angiopoietin-related protein|peroxisome proliferator-activated receptor (PPAR) gamma induced angiopoietin-related protein
Other designations: INSIG-2|INSIG2 membrane protein|insulin induced protein 2|insulin-induced gene 2 protein
Other designations: brain my036 protein|candidate tumor suppressor p33 ING1 homolog|inhibitor of growth protein 4
Other designations: uncharacterized protein C6orf203
DnaJ (Hsp40) homolog, subfamily C, member 27
Other designations: Ras-associated protein Rap1|dnaJ homolog subfamily C member 27|rab and DnaJ domain-containing protein
cytochrome P450, family 39, subfamily A, polypeptide 1
Other designations: 24-hydroxycholesterol 7-alpha-hydroxylase|cytochrome P450, subfamily XXXIX (oxysterol 7 alpha-hydroxylase), polypeptide 1
tumor necrosis factor receptor superfamily, member 12A
Other designations: FGF-inducible 14|fibroblast growth factor-inducible immediate-early response protein 14|tumor necrosis factor receptor superfamily member 12A|tweak-receptor|type I transmembrane protein Fn14
Other designations: ANG-4|angiopoietin-3|angiopoietin-4|dJ824F16.2 (angiopoietin 4)
eukaryotic translation initiation factor 3, subunit L
Other designations: eIEF associated protein HSPC021|eukaryotic translation initiation factor 3 subunit 6-interacting protein|eukaryotic translation initiation factor 3 subunit E-interacting protein|eukaryotic translation initiation factor 3 subunit L
Other designations: androgen-induced gene 1 protein
Other designations: MI-1-P synthase|MIP synthase|myo-inositol 1-phosphate synthase A1
Other designations: G2 and S phase-expressed protein 1|protein B99 homolog
Other designations: NAG/BC035112 fusion|NAG/FAM49A fusion|neuroblastoma-amplified gene protein|neuroblastoma-amplified sequence
DnaJ (Hsp40) homolog, subfamily B, member 11
Other designations: APOBEC1-binding protein 2|DnaJ protein 9|ER-associated DNAJ protein 3|ER-associated Hsp40 co-chaperone|ER-resident protein ERdj3|PWP1-interacting protein 4|dnaJ homolog subfamily B member 11|endoplasmic reticulum DNA J domain-containing protein 3
Other designations: pantothenic acid kinase 1
DnaJ (Hsp40) homolog, subfamily C, member 10
Other designations: ER-resident protein ERdj5|J-domain-containing protein disulfide isomerase-like protein|dnaJ homolog subfamily C member 10|endoplasmic reticulum DNA J domain-containing protein 5|macrothioredoxin|protein disulfide isomerase family A, member 19
Other designations: DNA damage-inducible transcript 4 protein|HIF-1 responsive protein RTP801|protein regulated in development and DNA damage response 1
UDP glucuronosyltransferase 1 family, polypeptide A1
Other designations: UDP glycosyltransferase 1 family, polypeptide A1|UDP-glucuronosyltransferase 1-1|UDP-glucuronosyltransferase 1-A|UDP-glucuronosyltransferase 1A1|UGT-1A|UGT1*1|UGT1-01|UGT1.1|bilirubin UDP-glucuronosyltransferase 1-1|bilirubin UDP-glucuronosyltransferase isozyme 1|bilirubin-specific UDPGT isozyme 1
DnaJ (Hsp40) homolog, subfamily B, member 12
Other designations: dnaJ homolog subfamily B member 12
cytochrome P450, family 2, subfamily W, polypeptide 1
Other designations: CYPIIW1|cytochrome P450 2W1
DnaJ (Hsp40) homolog, subfamily C, member 28
Other designations: dnaJ homolog subfamily C member 28
Other designations: COMM domain-containing protein 8
Other designations: N amino acid transporter 3|Na(+)-coupled neutral amino acid transporter 4|amino acid transporter A3|amino acid transporter system A3|sodium-coupled neutral amino acid transporter 4|system A amino acid transporter 3|system N amino acid transporter 3
angiogenic factor with G patch and FHA domains 1
Other designations: G patch domain-containing protein 7|angiogenic factor VG5Q|vasculogenesis gene on 5q protein
nudix (nucleoside diphosphate linked moiety X)-type motif 11
Other designations: DIPP-3-beta|DIPP3-beta|diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase 3-beta|diadenosine hexaphosphate hydrolase (AMP-forming)|diphosphoinositol polyphosphate phosphohydrolase 3, beta|diphosphoinositol polyphosphate phosphohydrolase 3-beta|hAps1|nucleoside diphosphate-linked moiety X motif 11|nudix motif 11
DnaJ (Hsp40) homolog, subfamily C, member 17
Other designations: dnaJ homolog subfamily C member 17
Other designations: EKI 2|ethanolamine kinase-like protein
Other designations: acyl-CoA oxidase-like protein|acyl-coenzyme A oxidase-like protein
serine palmitoyltransferase, long chain base subunit 3
Other designations: LCB 3|SPT 3|long chain base biosynthesis protein 2b|long chain base biosynthesis protein 3|serine palmitoyltransferase 3|serine palmitoyltransferase, long chain base subunit 2-like (aminotransferase 2)|serine-palmitoyl-CoA transferase 3
Other designations: alkCDase 3|alkaline CDase 3|alkaline dihydroceramidase SB89|alkaline phytoceramidase|phytoceramidase, alkaline
CCR4-NOT transcription complex, subunit 11
Other designations: CCR4-NOT transcription complex subunit 11|UPF0760 protein C2orf29
proline-rich nuclear receptor coactivator 2
G2/M-phase specific E3 ubiquitin protein ligase
Other designations: G2/M phase-specific E3 ubiquitin-protein ligase|G2/M-phase specific E3 ubiquitin ligase|PHD finger protein 7B
activating transcription factor 7 interacting protein
Other designations: ATF-interacting protein|ATF7-interacting protein|ATFa-associated modulator|MBD1-containing chromatin-associated factor 1|activating transcription factor 7-interacting protein 1
DnaJ (Hsp40) homolog, subfamily C, member 11
Other designations: dnaJ homolog subfamily C member 11|novel DnaJ domain-containing protein
ER degradation enhancer, mannosidase alpha-like 2
Other designations: ER degradation-enhancing alpha-mannosidase-like 2|ER degradation-enhancing alpha-mannosidase-like protein 2|ER degradation-enhancing-mannosidase-like protein 2
Other designations: E3 ubiquitin-protein ligase RNF130|g1-related zinc finger protein|goliath homolog
Other designations: acyl-coenzyme A thioesterase 13|hypothalamus protein HT012|thioesterase superfamily member 2
eukaryotic translation initiation factor 4E nuclear import factor 1
Other designations: 2610509L04Rik|eIF4E transporter|eIF4E-transporter|eukaryotic translation initiation factor 4E transporter
DnaJ (Hsp40) homolog, subfamily C, member 12
Other designations: J domain containing protein 1 (JDP1)|J domain protein 1|dnaJ homolog subfamily C member 12|j domain-containing protein 1
cytochrome P450, family 26, subfamily B, polypeptide 1
Other designations: cytochrome P450 26B1|cytochrome P450 retinoic acid-inactivating 2|cytochrome P450 retinoid metabolizing protein|cytochrome P450, subfamily XXVIB, polypeptide 1|retinoic acid-metabolizing cytochrome
Other designations: ERO1-L-beta|ERO1-like protein beta|endoplasmic oxidoreductin-1-like protein B|endoplasmic reticulum oxidoreductin-1-like protein B|oxidoreductin-1-L-beta
eukaryotic translation initiation factor 5A2
Other designations: eIF-5A-2|eukaryotic initiation factor 5A|eukaryotic translation initiation factor 5A-2
StAR-related lipid transfer (START) domain containing 7
Other designations: START domain containing 7|START domain-containing protein 7|gestational trophoblastic tumor protein 1|stAR-related lipid transfer protein 7, mitochondrial
solute carrier family 44 (choline transporter), member 2
Other designations: choline transporter-like protein 2|solute carrier family 44, member 2
Other designations: loop-tail protein 1 homolog|loop-tail-associated protein|strabismus 1|van Gogh-like protein 2|vang-like 2 (van gogh, Drosophila)|vang-like protein 2
cytochrome P450, family 20, subfamily A, polypeptide 1
Other designations: cytochrome P450 20A1|cytochrome P450 monooxygenase
pyruvate dehyrogenase phosphatase catalytic subunit 2
Other designations: PDPC 2|[Pyruvate dehydrogenase [acetyl-transferring]]-phosphatase 2, mitochondrial|protein phosphatase 2C, magnesium-dependent, catalytic subunit 2|pyruvate dehydrogenase phosphatase catalytic subunit 2|pyruvate dehydrogenase phosphatase isoenzyme 2|pyruvate dehydrogenase phosphatase, catalytic subunit 2
Other designations: FNIP1-like protein|O6-methylguanine-induced apoptosis 1 protein|folliculin-interacting protein 2
Other designations: TRB-3|neuronal cell death inducible putative kinase|neuronal cell death-inducible putative kinase|p65-interacting inhibitor of NF-kappa-B|p65-interacting inhibitor of NF-kappaB|tribbles homolog 3
cytochrome P450, family 4, subfamily F, polypeptide 11
Other designations: cytochrome P450 4F11|cytochrome P450, subfamily IVF, polypeptide 11
Other designations: 110 kDa actin filament-associated protein|actin filament-associated protein 1|actin filament-associated protein, 110 kDa
Other designations: myocardial ischemic preconditioning upregulated 1 ortholog
phenazine biosynthesis-like protein domain containing
Other designations: MAWD-binding protein|phenazine biosynthesis-like domain-containing protein
DnaJ (Hsp40) homolog, subfamily C, member 1
Other designations: DnaJ-like protein|dnaJ homolog subfamily C member 1|dnaJ protein homolog MTJ1
ATP-binding cassette, sub-family G (WHITE), member 8
Other designations: ATP-binding cassette sub-family G member 8|ATP-binding cassette, subfamily G, member 8|sterolin 2|sterolin-2
Other designations: differentiation-related gene 14 protein|limb region 1 homolog|limb region 1 protein homolog
nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, zeta
Other designations: I-kappa-B-zeta|IL-1 inducible nuclear ankyrin-repeat protein|Ikappa B-zeta variant 3|IkappaB-zeta|NF-kappa-B inhibitor zeta|ikB-zeta|ikappaBzeta|molecule possessing ankyrin repeats induced by lipopolysaccharide
hypoxia inducible factor 3, alpha subunit
Other designations: HIF3-alpha-1|PAS domain-containing protein 7|basic-helix-loop-helix-PAS protein MOP7|class E basic helix-loop-helix protein 17|hypoxia-inducible factor 3-alpha|inhibitory PAS domain protein|member of PAS protein 7
Other designations: apoptosis-enhancing nuclease|interferon stimulated exonuclease gene 20kDa-like 1|interferon-stimulated 20 kDa exonuclease-like 1
Other designations: EPS8-like protein 2|EPS8-related protein 2|epidermal growth factor receptor kinase substrate 8-like protein 2|epidermal growth factor receptor pathway substrate 8-related protein 2
cytochrome P450, family 3, subfamily A, polypeptide 43
Other designations: cytochrome P450 3A43|cytochrome P450, subfamily IIIA, polypeptide 43
fibronectin type III domain containing 4
Other designations: fibronectin type III domain-containing protein 4|fibronectin type III repeat-containing protein 1
Other designations: DDRGK domain-containing protein 1|Dashurin|UFM1-binding protein 1 containing a PCI domain
cytochrome P450, family 4, subfamily F, polypeptide 12
Other designations: CYPIVF12|cytochrome P450 4F12|cytochrome P450, subfamily IVF, polypeptide 12
Other designations: 3-keto acyl-CoA synthase ELOVL6|ELOVL FA elongase 6|ELOVL family member 6, elongation of long chain fatty acids (FEN1/Elo2, SUR4/Elo3-like, yeast)|elongation of very long chain fatty acids protein 6|fatty acid elongase 2|fatty acyl-CoA elongase|hELO2|long-chain fatty-acyl elongase|very-long-chain 3-oxoacyl-CoA synthase 6
ChaC, cation transport regulator homolog 1 (E. coli)
Other designations: ChaC, cation transport regulator-like 1|blocks Notch protein|botch|cation transport regulator-like protein 1|gamma-GCT acting on glutathione homolog 1
Other designations: cysteine-rich with EGF-like domain protein 2
Other designations: calmin|calponin like transmembrane domain protein|calponin-like transmembrane domain protein
UDP glucuronosyltransferase 2 family, polypeptide A3
Other designations: UDP-glucuronosyltransferase 2A3|UDPGT 2A3
Other designations: mammalian suppressor of tau pathology-2|nuclear protein UKp68|renal carcinoma antigen NY-REN-37|zinc finger CCCH domain-containing protein 14
DnaJ (Hsp40) homolog, subfamily C, member 22
Other designations: dnaJ homolog subfamily C member 22|wurst homolog
DnaJ (Hsp40) homolog, subfamily B, member 14
Other designations: dnaJ homolog subfamily B member 14
activating transcription factor 7 interacting protein 2
Other designations: ATF7-interacting protein 2|MBD1-containing chromatin associated factor 2|MBD1-containing chromatin-associated factor 2|activating transcription factor 7-interacting protein 2
phosphatidylinositol glycan anchor biosynthesis, class Z
Other designations: GPI mannosyltransferase 4|GPI mannosyltransferase IV|SMP3 mannosyltransferase|dol-P-Man dependent GPI mannosyltransferase|phosphatidylinositol glycan, class Z|phosphatidylinositol-glycan biosynthesis class Z protein
Other designations: HCV NS5A-transactivated protein 3|hepatitis C virus NS5A-transactivated protein 3|solute carrier family 35 member F5
ER degradation enhancer, mannosidase alpha-like 3
Other designations: ER degradation-enhancing -mannosidase-like protein 3|ER degradation-enhancing alpha-mannosidase-like 3|ER degradation-enhancing alpha-mannosidase-like protein 3|alpha-1,2-mannosidase EDEM3
DnaJ (Hsp40) homolog, subfamily C, member 5
Other designations: cysteine string protein alpha|dnaJ homolog subfamily C member 5
Other designations: apolipoprotein L domain-containing protein 1|vascular early response gene protein
Other designations: ras-related protein Rab-33B
RAD9-HUS1-RAD1 interacting nuclear orphan 1
Other designations: RAD9, HUS1, RAD1-interacting nuclear orphan protein 1|Rad9, Rad1, Hus1 interacting nuclear orphan|rAD9, RAD1, HUS1-interacting nuclear orphan protein
Other designations: activin beta E|activin beta-E chain|inhibin beta E chain
Other designations: angiopoietin-like protein 6|angiopoietin-related growth factor|angiopoietin-related protein 5|angiopoietin-related protein 6
eukaryotic translation initiation factor 2A, 65kDa
Other designations: 65 kDa eukaryotic translation initiation factor 2A|eukaryotic translation initiation factor 2A
Other designations: F-box domain protein|F-box only protein 30|F-box only protein, helicase, 18
Other designations: hydroxysteroid dehydrogenase-like protein 2|short chain dehydrogenase/reductase family 13C, member 1
DnaJ (Hsp40) homolog, subfamily C, member 30
Other designations: Williams Beuren syndrome chromosome region 18|dnaJ homolog subfamily C member 30|williams-Beuren syndrome chromosomal region 18 protein
eukaryotic translation initiation factor 1A domain containing
Other designations: eukaryotic translation initiation factor 1A domain-containing protein|probable RNA-binding protein EIF1AD
Other designations: acyl-CoA-binding domain-containing protein 6|acyl-Coenzyme A binding domain containing 6
Other designations: acyl-CoA retinol O-fatty-acyltransferase|diacylglycerol O-acyltransferase homolog 2|diacylglycerol O-acyltransferase-like protein 2|diglyceride acyltransferase 2|retinol O-fatty-acyltransferase
Other designations: muscle specific ring finger 2|muscle-specific RING finger protein 2|ring finger protein 29|tripartite motif-containing 55|tripartite motif-containing protein 55
Other designations: abhydrolase domain-containing protein 1|lung alpha/beta hydrolase 1
DnaJ (Hsp40) homolog, subfamily C, member 14
Other designations: LYST-interacting protein LIP6|dnaJ homolog subfamily C member 14|dnaJ protein homolog 3|dopamine receptor interacting protein|dopamine receptor-interacting protein of 78 kDa|hDj-3|human DnaJ protein 3
DnaJ (Hsp40) homolog, subfamily C, member 5 beta
Other designations: beta cysteine string protein|beta-CSP|cysteine string protein beta|dnaJ homolog subfamily C member 5B|dnaJ homolog subfamily C member X
Other designations: ATP binding domain 4|ATP-binding domain-containing protein 4|DPH6 homolog|diphthamide synthase|diphthamide synthetase|diphthine--ammonia ligase|protein DPH6 homolog
Other designations: AN1-type zinc finger protein 2A|arsenite inducible RNA associated protein
Other designations: leucine-rich repeat-containing protein 16B
Other designations: coiled-coil domain-containing protein 126
radical S-adenosyl methionine domain containing 2
Other designations: cytomegalovirus-induced gene 5 protein|radical S-adenosyl methionine domain-containing protein 2|viperin|virus inhibitory protein, endoplasmic reticulum-associated, interferon-inducible
Other designations: LEM domain protein 1|LEM domain-containing protein 1|cancer/testis antigen 50
tumor protein p53 inducible nuclear protein 1
Other designations: p53-dependent damage-inducible nuclear protein 1|p53-inducible p53DINP1|stress-induced protein|tumor protein p53-inducible nuclear protein 1
Other designations: dispanin subfamily B member 3|infantile convulsions and paroxysmal choreoathetosis|interferon induced transmembrane protein domain containing 1
Other designations: probable proline racemase|trans-3-hydroxy-l-proline dehydratase|trans-3-hydroxyl-L-proline dehydratase|trans-L-3-hydroxyproline dehydratase
Other designations: cell division cycle-associated protein 5|p35|sororin
cytochrome P450, family 2, subfamily U, polypeptide 1
Other designations: cytochrome P450 2U1|spastic paraplegia 49
forkhead-associated (FHA) phosphopeptide binding domain 1
Other designations: FHA domain-containing protein 1|forkhead-associated domain-containing protein 1
Other designations: DNA damage-inducible transcript 4-like protein|HIF-1 responsive protein RTP801-like|REDD-2|homolog of mouse SMHS1|protein regulated in development and DNA damage response 2|regulated in development and DNA damage response 2
nuclear undecaprenyl pyrophosphate synthase 1 homolog (S. cerevisiae)
Other designations: nogo-B receptor|transport and golgi organization 14 homolog
Other designations: liver-expressed antimicrobial peptide 2
cytochrome P450, family 2, subfamily R, polypeptide 1
Other designations: cytochrome P450 2R1|cytochrome P450, family 2, R1|vitamin D 25-hydroxylase
DnaJ (Hsp40) homolog, subfamily C, member 24
Other designations: 1700030A21Rik|CSL-type zinc finger-containing protein 3|DPH4 homolog (JJJ3, S. cerevisiae)|DPH4, JJJ3 homolog|diphthamide biosynthesis protein 4|dnaJ homolog subfamily C member 24|zinc finger, CSL domain containing 3|zinc finger, CSL-type containing 3
Other designations: PLD 4|choline phosphatase 4|phosphatidylcholine-hydrolyzing phospholipase D4|phospholipase D4
Other designations: PTE-2b|acyl-coenzyme A thioesterase 4|peroxisomal acyl coenzyme A thioester hydrolase Ib|peroxisomal acyl-CoA thioesterase 2B|peroxisomal long-chain acyl-CoA thioesterase Ib
Other designations: 5-hydroxy-L-lysine kinase|5-hydroxylysine kinase|aminoglycoside phosphotransferase domain containing 1|aminoglycoside phosphotransferase domain-containing protein 1
acyl-CoA synthetase medium-chain family member 2A
Other designations: Homolog of rat kidney-specific (KS)|acyl-coenzyme A synthetase ACSM2A, mitochondrial|butyrate--CoA ligase 2A|butyryl-coenzyme A synthetase 2A|middle-chain acyl-CoA synthetase 2A
cytochrome P450, family 4, subfamily F, polypeptide 22
Other designations: cytochrome P450 4F22|cytochrome P450, family 2, subfamily E, polypeptide 2 homolog
Other designations: transmembrane protein C1orf162
Other designations: cell growth-inhibiting protein 7|ovarian cancer-related protein 10-2|serologically defined colon cancer antigen 33 like|teashirt family zinc finger 2|teashirt homolog 2|zinc finger protein 218
cytidine monophosphate (UMP-CMP) kinase 2, mitochondrial
Other designations: UMP-CMP kinase 2, mitochondrial|cytidylate kinase 2|mitochondrial UMP-CMP kinase|nucleoside-diphosphate kinase|thymidine monophosphate kinase 2|thymidylate kinase family LPS-inducible member
DnaJ (Hsp40) homolog, subfamily C, member 19
Other designations: homolog of yeast TIM14|mitochondrial import inner membrane translocase subunit TIM14
junction mediating and regulatory protein, p53 cofactor
Other designations: WAS protein homology region 2 domain containing 1-like 3|junction-mediating and -regulatory protein|junction-mediating and regulatory protein
DnaJ (Hsp40) homolog, subfamily C, member 21
Other designations: DnaJ homology subfamily A member 5|JJJ1 DnaJ domain protein homolog|dnaJ homolog subfamily A member 5|dnaJ homolog subfamily C member 21
Other designations: START domain-containing protein 15|StAR-related lipid transfer (START) domain containing 15|acyl-CoA thioester hydrolase 12|acyl-coenzyme A thioesterase 12|cytoplasmic acetyl-CoA hydrolase 1|cytosolic acetyl-CoA hydrolase|hCACH-1
eukaryotic translation initiation factor 5A-like 1
Other designations: eukaryotic translation initiation factor 5A pseudogene 1|eukaryotic translation initiation factor 5A-1-like
DnaJ (Hsp40) homolog, subfamily B, member 7
Other designations: dnaJ homolog subfamily B member 7|novel DnaJ domain protein
long intergenic non-protein coding RNA 342
Other designations: lysophospholipase|phospholipase A2|phospholipase B|phospholipase B/lipase|phospholipase B1, membrane-associated
Other designations: zinc finger protein 533
Other designations: GPI gamma-4|GPI-gamma 4|ras-GEF domain-containing family member 1B
Other designations: GTP-binding protein REM 2|Rad and Gem-related 2 (rat homolog)|rad and Gem-like GTP-binding protein 2
Other designations: 15 kDa interferon-responsive protein|interferon responsive gene 15|lumenal domain like LAP1|lumenal domain-like LAP1|torsin-1A-interacting protein 2
DnaJ (Hsp40) homolog, subfamily B, member 8
Other designations: dnaJ homolog subfamily B member 8
methylmalonic aciduria (cobalamin deficiency) cblA type
Other designations: methylmalonic aciduria type A protein, mitochondrial
basic helix-loop-helix family, member a15
Other designations: MIST-1|basic helix-loop-helix domain containing, class B, 8|class A basic helix-loop-helix protein 15|class B basic helix-loop-helix protein 8|class II bHLH protein MIST1|muscle, intestine and stomach expression 1
Other designations: 76 kDa protein|LAMA-like protein 2|PLB homolog 2|lamina ancestor homolog 2|mannose-6-phosphate protein associated protein p76|phospholipase B domain-containing protein 2|phospholipase B-like 2 32 kDa form|phospholipase B-like 2 45 kDa form|putative phospholipase B-like 2
caspase 16, apoptosis-related cysteine peptidase (putative)
Other designations: putative caspase-14-like protein|putative caspase-16
cytochrome P450, family 4, subfamily Z, polypeptide 1
Other designations: CYPIVZ1|cytochrome P450 4Z1
Other designations: BHD skin lesion fibrofolliculoma protein|birt-Hogg-Dube syndrome protein
DnaJ (Hsp40) homolog, subfamily C, member 18
Other designations: dnaJ homolog subfamily C member 18
CCR4-NOT transcription complex, subunit 6-like
Other designations: CCR4-NOT transcription complex subunit 6-like|carbon catabolite repressor protein 4 homolog B
eukaryotic translation initiation factor 4E family member 1B
Other designations: eukaryotic translation initiation factor 4E type 1B
Other designations: angiopoietin-like protein 5|angiopoietin-related protein 5
Other designations: FERM domain-containing protein 3|band 4.1-like protein 4|band 4.1-like protein 4O|ovary type protein 4.1|protein 4.1O
cytochrome P450, family 4, subfamily X, polypeptide 1
nuclear paraspeckle assembly transcript 1 (non-protein coding)
nudix (nucleoside diphosphate linked moiety X)-type motif 7
Other designations: peroxisomal coenzyme A diphosphatase NUDT7
glycerophosphodiester phosphodiesterase domain containing 1
Other designations: glycerophosphodiester phosphodiesterase 4|glycerophosphodiester phosphodiesterase domain-containing protein 1
cytochrome P450, family 4, subfamily A, polypeptide 22
Other designations: CYPIVA22|cytochrome P450 4A22|cytochrome P450 4A22K|fatty acid omega-hydroxylase|lauric acid omega-hydroxylase
DnaJ (Hsp40) homolog, subfamily C, member 5 gamma
Other designations: cysteine string protein-gamma|dnaJ homolog subfamily C member 5G|gamma cysteine string protein|gamma-CSP|gamma-cysteine string protein
cytochrome P450, family 4, subfamily V, polypeptide 2
eukaryotic translation initiation factor 4E family member 3
Other designations: eukaryotic translation initiation factor 4E type 3
eukaryotic translation initiation factor 4B pseudogene 1
cytochrome P450, family 27, subfamily C, polypeptide 1
Other designations: cytochrome P450 27C1|cytochrome P450, family 27, subfamily C, polypeptide 13
Other designations: alkCDase 2|alkaline CDase 2|ceramide hydrolase|haCER2
cytochrome P450, family 26, subfamily C, polypeptide 1
Other designations: cytochrome P450 26C1
insulin-like growth factor binding protein-like 1
Other designations: IGFBP-related protein 10|insulin-like growth factor binding protein related protein 4|insulin-like growth factor-binding protein-like 1|insulin-like growth factor-binding-related protein 4
acyl-CoA synthetase medium-chain family member 2B
Other designations: acyl-CoA synthetase medium-chain family member 2|acyl-coenzyme A synthetase ACSM2B, mitochondrial|butyrate--CoA ligase 2B|butyryl-coenzyme A synthetase 2B|middle-chain acyl-CoA synthetase 2B|xenobiotic/medium-chain fatty acid-CoA ligase HXM-A|xenobiotic/medium-chain fatty acid:CoA ligase
spindle and kinetochore associated complex subunit 2
Other designations: family with sequence similarity 33, member A|spindle and KT (kinetochore) associated 2|spindle and kinetochore-associated protein 2
Other designations: ankyrin repeat domain-containing protein 37|hLrp2bp|low density lipoprotein receptor-related protein binding protein|low-density lipoprotein receptor-related protein 2-binding protein
natural killer cell cytotoxicity receptor 3 ligand 1
Other designations: B7 homolog 6|natural cytotoxicity triggering receptor 3 ligand 1|putative Ig-like domain-containing protein DKFZp686O24166/DKFZp686I21167
DnaJ (Hsp40) homolog, subfamily B, member 13
Other designations: 1700014P03Rik|DnaJ (Hsp40) related, subfamily B, member 13|DnaJ-like protein|dnaJ homolog subfamily B member 13|radial spoke 16 homolog A|testis and spermatogenesis cell-related protein 6|testis spermatocyte apoptosis-related gene 6 protein|testis spermatogenesis apoptosis-related gene 3 protein|testis spermatogenesis apoptosis-related gene 6 protein|testis spermatogenesis apoptosis-related protein 6
Other designations: cancer-up-regulated gene 2 protein|cancer-upregulated gene 2
Other designations: inscuteable spindle orientation adaptor protein|protein inscuteable homolog
DnaJ (Hsp40) homolog, subfamily B, member 3
Other designations: dnaJ homolog subfamily B member 3
Other designations: serine/threonine kinase Pim-3|serine/threonine-protein kinase pim-3
eukaryotic translation initiation factor 2 alpha kinase 4
Other designations: GCN2 eIF2alpha kinase|GCN2-like protein|eukaryotic translation initiation factor 2-alpha kinase 4|general control nonderepressible 2
DnaJ (Hsp40) homolog, subfamily C , member 25
Other designations: DnaJ-like protein|dnaJ homolog subfamily C member 25
Other designations: DNAJC25-GNG10 protein|DNAJC25-GNG10 readthrough transcript
Other designations: CTE-I|CTE-Ib|acyl-coenzyme A thioesterase 1|inducible cytosolic acyl-coenzyme A thioester hydrolase|long chain acyl-CoA hydrolase|long chain acyl-CoA thioester hydrolase
Other designations: putative acyl-CoA thioesterase 6|putative acyl-coenzyme A thioesterase 6
eukaryotic translation initiation factor 3, subunit C-like
Other designations: eIF3 p110|eIF3c|eukaryotic translation initiation factor 3 subunit 8|eukaryotic translation initiation factor 3 subunit C|eukaryotic translation initiation factor 3 subunit C-like protein|eukaryotic translation initiation factor 3, subunit 8, 110kDa-like
Other designations: C-C chemokine receptor type 2|MCP-1 receptor|monocyte chemoattractant protein 1 receptor|monocyte chemotactic protein 1 receptor
GO_0004197 (EC: IBA); GO_0005737 (EC: IBA); GO_0030968 (EC: IEA); GO_0042981 (EC: IEA); GO_0050727 (EC: IBA, Qualifier: NOT); GO_0070059 (EC: IBA); GO_0072557 (EC: IBA, Qualifier: NOT); GO_0072559 (EC: IBA, Qualifier: NOT); GO_0097169 (EC: IBA, Qualifier: NOT); GO_0097194 (EC: IBA, Qualifier: NOT)
Other designations: caspase 12 pseudogene 1|inactive caspase-12
A representation that is either the output of a clinical history taking or a physical examination or an image finding, or some combination thereof.
The totality of all processes through which a given disease instance is realized.
replace 'OBI:occurrence of disease', need to add logical definition The axioms of OBI occurence of disease: Equivalent classes: realizes some disease Superclasses: 'has part' some 'pathologic process' 'has participant' some (organism and ('has role' some 'host of immune response role')) biological_process realizes some 'host of immune response role'
The representation of a conclusion of a diagnostic process.
A changing process in which cells become to have neoplastic quality.
A time quality inhering in a bearer by virtue of how long the bearer has existed.
A composite chromatic quality composed of hue, saturation and intensity parts.
A scalar optical property that is the intensity, value or amount of perceived light.
A single physical entity inhering in an bearer by virtue of the bearer's quantities or relative ratios of subparts
A physical quality inhering in a bearer by virtue of the bearer's orientation in space.
A physical quality inhering in a bearer by virtue of the bearer's resistance to pressure, being broken, or pierced
A spatial quality inhering in a bearer by virtue of the bearer's exhibiting repetition of placement of its parts.
A quality inhering in a bearer by virtue of the whether the bearer differs from normal or average.
The number of entities of this type that are part of the whole organism.
A quality of a single process inhering in a bearer by virtue of the bearer's movement or variation characterized by the regular recurrence or alternation of different quantities or conditions.
A rhythm quality inhering in a bearer by virtue of the repetitiveness of bearer's rhythm.
A quality that exists by virtue of being a particular point in the time of a cycle.
A morphology quality inhering in a bearer by virtue of the bearer's physical magnitude.
A 1-D extent quality inhering in a bearer by virtue of the bearer's vertical dimension of extension.
A 1-D extent quality which is equal to the distance between two points.
A physical quality that inheres in a bearer by virtue of the proportion of the bearer's amount of matter.
A physical attribute entity inhering in a bearer that has mass near a gravitational body.
A morphology quality inhering in a bearer by virtue of the bearer's relative position, shape, arrangements and connectivity of an organism's various parts; the pattern underlying its form.
A physical attribure of the thermal energy of a system.
A quality in which events occur in sequence.
An organismal quality inhering in a bearer or a population by virtue of the bearer's disposition to survive and develop normally or the number of surviving individuals in a given population.
A color hue with high wavelength of the long-wave end of the visible spectrum, evoked in the human observer by radiant energy with wavelengths of approximately 630 to 750 nanometers.
A color brightness which is relatively low.
A hardness quality of being rigid and resistant to pressure.
A hardness quality of giving little resistance to pressure.
A quality of a process inhering in a bearer by virtue of the bearer's having a sudden onset, sharp rise, and short course.
A quality of a single process inhering in a bearer by virtue of the bearer's occurring or appearing again or repeatedly.
A quality inhering in a bearer by virtue of the bearer's deviation from normal or average.
A quality inhering in a bearer by virtue of the bearer's exhibiting no deviation from normal or average.
A duration quality of a process which is relatively high.
A duration quality of a process which is relatively low.
A rhythm quality inhering in a bearer by virtue of the bearer's lacking rhythm.
A rhythm quality inhering in a bearer by virtue of the bearer's having rhythm.
A length quality which is relatively large.
A length quality which is relatively small.
An increased size quality inhering in a bearer by virtue of the bearer's exhibiting enlargement of a cell or constituent group of cells (for example, organ).
A size quality which is relatively high.
A structural quality inhering in a bearer whose structure deteriorates or is lost over time due to an active pathological process.
A 1-D extent quality which is equal to the dimension through an object as opposed to its length or width.
A 3-D extent quality inhering in a bearer by virtue of the bearer's amount of 3-dimensional space it occupies.
A structural quality inhering in a bearer by virtue of the bearer's disposition to being permeated or pervaded by a gas or liquid (as by osmosis or diffusion).
A physical quality inhering in a bearer by virtue of the bearer's rate of doing work.
A physical quality that inheres in a bearer by virtue of the bearer's amount of force per unit area it exerts.
A physical quaility inhering in a bearer by virtue of the bearer's rate of change of momentum.
A concentration quality inhering in a bearer by virtue of the bearer's exhibiting concentration.
A concentration which is higher relative to the normal or average.
A concentration which is lower relative to the normal or average.
A quality inhering in a bearer by virtue of the bearer's power or force.
A process quality inhering in a bearer by virtue of the bearer's magnitude of the temporal extent between the starting and ending point.
A 2-D extent quality inhering in a bearer by virtue of the bearer's two dimensional extent.
A duration which has regular start and/or end times.
A duration quality of a process inhering in a bearer by virtue of the bearer's duration which has irregular start and/or end times.
A viability quality inhering in a bearer by virtue of the cessation of the bearer's life.
An medium acidity quality inhering in a solution by virtue of the bearer's a high concentration of H+ ions.
An medium acidity quality inhering in a solution by virtue of the bearer's a low concentration of H+ ions.
A composition quality inhering in an bearer by virtue of the bearer's being encrusted or impregnated with calcium carbonate (CHEBI:3311).
A quality inhering in a cell's plasma membrane by virtue of the electrical potential difference across it.
A quality that is equal to the potential energy per unit charge associated with a static (time-invariant) electric field, also called the electrostatic potential.
A physical quality inhering in a bearer by virtue of the bearer's motion characteristic.
A permeability which is relatively high.
A size quality inhering in a bearer by virtue of a part or parts of the bearer's being decreased in size due to reduction in tissue mass through wasting.
A spatial pattern inhering in a bearer by virtue of the bearer's being gathered or tending to gather into a mass or whole.
A quality of single process inhering in a bearer by virtue of whether the bearer is essential or indispensable.
A necessity quality inhering in a process by virtue of the bearer's being essential or indispensable.
A necessity quality inhering in a process by virtue of the bearer's being non-essential or dispensable.
A composition quality inhering in a bearer by virtue of the bearer's containing granules.
A concentration quality inhering in a bearer by virtue of the bearer's containing acid (hydrogen ions).
A structural quality inhering in a bearer by virtue of the bearer's being fibrous tissue that replaces normal tissue destroyed by injury or disease.
A physical quality inhering in a bearer by virtue the bearer's disposition to being water-repellent; tending to repel and not absorb water.
A physical quality inhering in a bearer by virtue the bearer's disposition to having an affinity for water; it is readily absorbing or dissolving in water.
A physical quality inhering in a bearer by virtue of the bearer's participation in movement.
A number quality which is relatively many.
A structural quality which is held by a bearer when the latter's disposition the presence of abnormally proliferating masses of cells.
A structural quality inhering in a bearer by virtue of the bearer exhibiting deterioration of its structure.
A molecular quality that arises from the molecular attraction exerted between two atoms or compounds.
A quality of a single process inhering in a bearer by virtue of the bearer's having an onset and time course between acute and chronic.
An affinity inhering in a tissue constituent by virtue of the bearer exhibiting a molecular interaction for basic dyes under specific ph conditions.
A disposition inhering in a tumour by virtue of the bearer's disposition not to progress, invade surrounding tissues or metastasize.
A disposition inhering in a tumour by virtue of the bearer's disposition to progress, invade surrounding tissues or metastasize.
A disposition inhering in a tumour by virtue of the bearer's disposition to spread and invade distant tissues.
A compositional quality inhering in an bearer by virtue of the bearer's infiltration by leukocytes, local edema and accumulation of plasma proteins.
A composition quality inhering in a bearer by virtue of the bearer's containing excess lipid.
A disposition inhering in a tumour by virtue of the bearer's disposition to invade surrounding tissues.
A disposition inhering in a tumour by virtue of the bearer's disposition not to invade surrounding tissues.
A physical quality inhering in a bearer by virtue of the bearer's rate of change of the position.
A structural quality of the collection or massing of one physical object within another physical object.
An increased number of physical objects that are accumulated within another physical object usually as a result of a failure to break down or remove objects in a timely manner.
A temporal distribution pattern of process occurrences within a regulation/reference process.
A quality that inheres in a bearer in virtue of its realizing one of its functions.
A quality of an physical object that is currently realizing one of its functions.
A quality of a physical object that is currently realizing none of its functions.
Having both hydrophilic and hydrophobic (or lipophilic) groups.
A disposition inhering in a tumour by virtue of the bearer's disposition to spontaneously arise.
The ability of a process to produce its output.
A decrease in the ability of a process to produce its output.
A increase in the ability of a process to produce its output.
A protein that is a translation product of the human LPL gene or a 1:1 ortholog thereof. Category=gene.
This gene encodes a nuclear-localized E3 ubiquitin ligase. The encoded protein can promote tumor formation by targeting tumor suppressor proteins, such as p53, for proteasomal degradation. This gene is itself transcriptionally-regulated by p53. Overexpression or amplification of this locus is detected in a variety of different cancers. There is a pseudogene for this gene on chromosome 2. Alternative splicing results in a multitude of transcript variants, many of which may be expressed only in tumor cells. [provided by RefSeq, Jun 2013]
P53 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the PERK. PERK generally plays a endoplasmic reticulum membrane stress sensor role.
Phospholipase transport to lysosome is a subtype of molecule transport: A process of the directed movement of phospholipase to the lysosome.
Moving solid is a subtype of moving. A process that change the location of the solid. .
Generating periodic motion is a subtype of generating motion: A process that generates the directed movement in which the object decreases in volume.
Any biological process that results in permanent cessation of all vital functions of a cell. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
Toxic course is a subtype of process sequence: A series of process in an organism from latent to the manifestation of toxicity, which is not part of the life of the organism.
Changing membrane fluidity is a subtype of changing fluidity: A process that changes the fluidity of the membrane. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
changing membrane fluidity [Phospholipidosis]
Cationic amphiphilic drugs and phospholipid storage disorder.
Generating signal is a subtype of generating: A process that produces a signal as an output.
PPARalpha activation is a subtype of activating nuclear receptor: A process that changes the activity of the activating PPAR alpha ( (Peroxisome Proliferator Activated Receptor Alpha)) with a nuclear receptor role to be higher.
activating peroxisome proliferator-activated receptor alpha
Changing sensitivity is a subtype of changing quality: A process that changes the sensitivity of the object.
Hypofunction of detoxification is a subtype of hypofunctioning: A process that performs a decreased or insufficient detoxification. This entity is a specific course-dependent process. This process can constitute the course of Hepatic encephalopathy.
hypofunction of detoxification [hepatic encephalopathy]
Increasing ammonia concentration in blood is a subtype of increasing concentration: A process that changes the ammonia concentration in the blood to be higher. This entity is a specific course-dependent process. This process can constitute the course of Hepatic encephalopathy.
increasing ammonia concentration in blood [Hepatic encephalopathy]
Arole played by the entity that isoenergetic transfer of ubiquitin from one protein to another via the reaction X-ubiquitin + Y -> Y-ubiquitin + X, where both the X-ubiquitin and Y-ubiquitin linkages are thioester bonds between the C-terminal glycine of ubiquitin and a sulfhydryl side group of a cysteine residue.
Generating substance is a subtype of generating: A process that produces a substance as an output.
Changing activity is a subtype of changing quality: A process that changes the activity of the object.
Inactivation is a subtype of changing activity: A process that changes the activity of the object to be lower.
Changing direction is a subtype of changing quality: A process that changes the direction of the object.
Molecular activation is a subtype of activating: A process that changes the activity of the moleule to be higher.
Changing bond is a subtype of changing between operands: A process that changes a bond between objects.
Changing disulfide bond is a subtype of changing bond: A process that changes a disulfide bond which is a covalent bond mediated by 2 sulfur atoms.
Integrated signaling pathway is a subtype of pathway: Sequence of linked reactions, which has signaling pathway and gene regulated pathway.
1. signal detection (acceptance), 2. signal transduction, 3. gene regulation (genetic information conversion process), 4. celllular process execution This entity covers from 1, 2, and 3.
The totality of all processes through which eosinogranular degeneration is realized.
eosinophilic granular degeneration [toxic course]
Excess peroxisomes are degraded by autophagic machinery in mammals. Atg7, an essential gene for autophagy, plays a pivotal role in the degradation of excess peroxisomes in mammals. The autophagic machinery is essential for the selective clearance of excess peroxisomes in mammals.
Hepatic fibrosis dependent gene is a subtype of toxic course dependent chemical entity. This gene can participate in the course of hepatic fibrosis as a gene product. Gene profile:Human/in vitro/Hepatocyte/
hepatic fibrosis dependent molecule (human in vitro)
Dysfunction of calcium transport is a subtype of dysfunctioning: A process that performs an abnormal and incomplete calcium transport. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
dysfunction of calcium transport [Cell death]
CREBPH activation is a subtype of molecular activation: A process that changes the activity of the CRBPH to be higher.
Rifampicin, bosentan, and troglitazone directly inhibit bile salt export pump (BSEP).
The endothelin antagonist bosentan inhibits the canalicular bile salt export pump BSEP, which causes intracellular accumulation of cytotoxic bile salts and bile salt induced liver cell damage
Cholestasis dependent process is a subtype of toxic course dependent process: A process that can constitute the course of cholestasis.
Hypofunction of extracellular matrix disassembly is a subtype of hypofunction of decomposing: A process that performs a decreased or insufficient extracellular matrix disassembly.
hypofunction of extracellular matrix disassembly
A role played by the entity which regulates tranport process.
Changing disulfide bond is a subtype of changing bond: A process that changes a disulfide bond which is a covalent bond mediated by 2 sulfur atoms. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
A role played by the entity that has a toxic effect.
Increasing weight is a subtype of changing weight: A process that changes the weight of the object to be higher.
Inreasing blood ALP concentration is a subtype of increasing concentration: A process that changes the bilirubin concentration in the blood to be higher. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
inreasing blood ALP concentration [cholestasis]
Mitochondrial dysfunction is a subtype of dysfunctioning: A process that performs an abnormal and incomplete mitochondrial function. This entity is a specific course-dependent process. This process can constitute the course of Oxidative stress.
mitochondrial dysfunction [Oxidative stress]
ATF6 (golgi apparatus) (canonical)[ER stress]
Hypofunction of bile acid and bile salt transport is a subtype of hypofunction of transport: A process that performs a decreased or insufficient bile acid and bile salt transport.
hypofunction of bile acid and bile salt transport
Cleavage of ATF6-alpha by S2P is a subtype of proteolysis: A process n which ATF6-alpha is cleaved by endopeptidase S2P( MBTPS2). Site-2 cleavage comes after site-1 cleavage.
De-differentiation confers multidrug resistance via noncanonical PERK-Nrf2 signaling.
Cleavage of ATF6-alpha by S1P is a subtype of proteolysis: A process in which ATF6-alpha is cleaved by endopeptidase S1P( MBTPS1).
Cleavage of ATF6-alpha by S1P is a subtype of proteolysis: A process in which ATF6-alpha is cleaved by endopeptidase S1P( MBTPS1). This entity is a specific course-dependent process. This process can constitute the course of ER stress.
cleavage of ATF6-alpha by S1P [ER stress]
Inflammatory cytokine gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature inflammatory cytokine gene product or products (proteins or RNA). This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
inflammatory cytokine gene expression [Lipidosis]
ChREBP activation is a subtype of activating nuclear receptor: A process that changes the activity of the activating ChREBP to be higher.
A monoatomic or polyatomic species having one or more elementary charges of the proton.
Translocation of ATF6 from the cytosol to the nucleus is a subtype of nuclear transport: A process that of the directed movement of ATF6 from the cytoplasm to the nucleus.
Translocation of ATF6 from the cytosol to the nucleus
Increasing liver weight is a subtype of increasing weight: A process that changes the weight of the liver to be higher.
Translocation of ATF6 from the cytosol to the nucleus is a subtype of nuclear transport: A process that of the directed movement of ATF6 from the cytoplasm to the nucleus. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Translocation of ATF6 from the cytosol to the nucleus [ER stress]
A role played by the entity which regulatess bile acid transport process.
Combining role with an extracellular or intracellular signal and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity or state as part of signal transduction.
Combining role with an extracellular messenger (called a death ligand), and transmitting the signal from one side of the plasma membrane to the other to initiate apoptotic or necrotic cell death.
lysosome damage is a subtype of organelle damage.
Ground glass appearance [Liver PathologicalFindings] is a type of finding observed in hepatocyte cytoplasm. Based on the pathological morphology, lesions are observed as a frosted-like change in whole or most of the hepatocytes.
Monochromatic eosinophilic change across the whole or most of the hepatocyte. It is often observed as a changing response to the hepatic metabolism enzyme inducer such as phenobarbital. In electron microscopy, it is regarded as prominent proliferation of smooth endoplasmic reticulum, dispersion of rough endoplasmic reticulum, with decrease of stored glycogen.
ground glass appearance [Liver Pathological Findings]
A process in which a signal to eIF2a is transduced by PERK. This process is dependent on the translation attenuation and can constitute the course of ER stress.
PERK signaling to eIF2a [ER stress - translation attenuation]
A process in which a signal to eIF2a is transduced by PERK. This entity is a specific course-dependent process. This process can constitute the course of PERK - eIF2A pathway.
PERK signaling to eIF2a [PERK - eIF2A pathway]
PERK dimerization is a subtype of protein dimerization: The formation of a PERK dimer, a macromolecular structure consists of two noncovalently associated identical or nonidentical subunits. This entity is a specific course-dependent process. This process can constitute the course of ER stress and involves inflammation.
PERK dimerization [ER stress - translation attenuation]
A role played by the protein that has a structure of misfolding
Cellular tissue is a subtype of object aggregate that consists of cells or tissues.
Changing cytoskeleton is a subtype of changing structure: A process that changes the structure of cytoskeleton. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
PERK signaling (integrated pathway) is a subtype of integrated signaling pathway: Sequence of linked reactions, which has ATF6 signaling and gene regulation pathway.
Negative regulation of formation of cytoplasmic translation initiation complex is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of formation of cytoplasmic translation initiation complex.
negative regulation of formation of translation initiation complex
negative regulation of formation of cytoplasmic translation initiation complex
organelle damage is a subtype of damaging.
The chemical reactions and pathways resulting in the breakdown of sphingolipids, any of a class of lipids containing the long-chain amine diol sphingosine or a closely related base (a sphingoid).
Insulin deficiency is a subtype of malfunctioning process: A process that lacks performing the insulin function required.
natural killer cell activation is a subtype of macrophage activation: A change in morphology and behavior of a natural killer (NK) cell resulting from exposure to a cytokine, chemokine, cellular ligand, or soluble factor. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense).
natural killer cell activation [Phospholipidosis (excessive defense)]
Insulin deficiency is a subtype of malfunctioning process: A process that lacks performing the insulin function required. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Increasing GDF15 level is a subtype of increasing quantity: A process that changes the amount of GDF15 level to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
increasing GDF15 level [mitochondrial disorder]
Treatment with alcohol also increased the levels of secreted GDF15 in supernatants of cultured hepatocytes. We next investigated the effect of mitochondrial dysfunction on GDF15 expression in hepatocytes. Inhibition of the mitochondrial OXPHOS complex using oligomycin or rotenone significantly increased Gdf15 expression and GDF15 secretion by cultured hepatocytes. Hepatic Gdf15 expression and serum levels of GDF15 were remarkably increased in alcohol-fed mice. It may drive the protective effect against alcohol- or CCl4-induced liver injury. This evidence suggests that mitochondrial dysfunction may be a double-edged sword, as it may affect disease progression as well as protection.
ITGB3 (predicted)(human)[Phospholipidosis]
The prediction from our hypothetical model is that when αVβ3 integrin is persistently ligated/activated, it will prevent macrophage differentiation into the foam cell phenotype. Conversely, blocking of the αVβ3 receptor may lead to up-regulation of scavenger receptor expression and increased foam cell formation.
Affinity of talin-1 for the β3-integrin cytosolic domain is modulated by its phospholipid bilayer environment
c-Abl is an upstream regulator of acid sphingomyelinase in apoptosis induced by inhibition of integrins αvβ3 and αvβ5.
Calcium oscillation and phosphatidylinositol 3-kinase positively regulate integrin alpha(IIb)beta3-mediated outside-in signaling.
Transcriptional Regulation of Cytosolic Sulfotransferase 1C2 by Intermediates of the Cholesterol Biosynthetic Pathway in Primary Cultured Rat Hepatocytes.
predicted gene by Support Vector Machine (SVM) using human primary hepatocyte
ECM2 - tumor progression marker (predicted)(human) [Glutathione depletion]
Identification of the Consistently Altered Metabolic Targets in Human Hepatocellular Carcinoma: We correlated each of the 634 identified metabolic genes with 4 consistent progression markers, namely ECM2 and MMP9, which are related to invasion or metastasis.
A role played by the entity that shows an expression change according to the degree of tumor progression.
A role played by the entity which inhibits bile acid transport process.
Bile pigment deposition is a subtype of accumulation of pigments: The aggregation of bile pigmentin a particular location in an organism, tissue or cell.
Changing membrane fluidity is a subtype of changing fluidity: A process that changes the fluidity of the membrane. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
changing membrane fluidity [Cholestasis]
Hypofunction of transmembrane transport is a subtype of hypofunction of transport: A process that performs a decreased or insufficient transmembrane transport.
Hypofunction of transmembrane transport is a subtype of hypofunction of transport: A process that performs a decreased or insufficient transmembrane transport. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
hypofunction of transmembrane transport [Cholestasis]
Dnajb9 apoptosis inhibitor (rat)[ER stress]
Increasing acetyl CoA is a subtype of increasing quantity: A process that changes the amount of acetyl CoA to be larger.
A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
meloxicam - apotosis inducing factor [ER stress]
Endoplasmic reticulum proliferation in hepatocyte is a subtype of increasing number of hepatocyte organelle: A process that becomes larger in the number of endoplasmic reticulum in hepatocyte(s).
increasing number of hepatocellular endoplasmic reticulum
endoplasmic reticulum proliferation in hepatocyte
Endoplasmic reticulum proliferation in hepatocyte is a subtype of increasing number of hepatocyte organelle: A process that becomes larger in the number of endoplasmic reticulum in hepatocyte(s). This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
increasing number of hepatocellular endoplasmic reticulum This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
Increasing number of objects is a subtype of changing: A process that becomes larger in the number of physical objects.
Maintaining permeability is a subtype of changing permeability: A process that changes the permeability of the membrane to be lower.
Hyperfunction of fatty acid beta-oxidation is a subtype of hyperfunction of fatty acid oxidation: A process that performs an excessive fatty acid beta-oxidation.
hyperfunction of fatty acid beta-oxidation
Increasing liver weight is a subtype of increasing weight: A process that changes the weight of the liver to be higher. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
increasing liver weight [Eosinophilic granular degeneration]
A fatty acid oxidation process in which the methyl group at the end of the fatty acid molecule (the omega carbon) is first oxidized to a hydroxyl group, then to an oxo group, and finally to a carboxyl group. The long chain dicarboxylates derived from omega-oxidation then enter the beta-oxidation pathway for further degradation.
Hyperfunction of lipid oxidation is a subtype of hyperfunction of lipid catabolic process: A process that performs an excessive lipid degradation.
Hyperfunction of fatty acid oxidation is a subtype of hyperfunction of lipid oxidation: A process that performs an excessive lipid oxidation.
Hyperfunction of lipid degradation is a subtype of hyperfunction of decompoing: A process that performs an excessive lipid degradation.
Removing ceramide by Kupffer cell or macrophage is a subtype of removing: A process that takes a ceramide from a cell by Kupffer cells or macrophages . This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (sphingomyelin disorder).
hyperfunction of cerramide phagocytosis by Kupffer cells or macrophges [Phospholipidosis-sphingomyelin disorder]
Increasing demand for response to oxidative stress is a subtype of increasing the demand for response to stress: A process that changes the functional demand for the response to the oxidative stress to be higher.
increasing demand for response to oxidative stress
Increasing demand for response to oxidative stress is a subtype of increasing the demand for response to stress: A process that changes the functional demand for the response to the oxidative stress to be higher. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
increasing demand for response to oxidative stress [Eosinophilic granular degeneration]
Peroxisomal proliferation in hepatocyte is a subtype of hepatocyte organelle proliferation: A process that becomes larger in the number of peroxisome in hepatocyte(s).
increasing peroxisome number in hepatocytes
Peroxisomal proliferation in hepatocyte is a subtype of hepatocyte organelle proliferation: A process that becomes larger in the number of peroxisome in hepatocyte(s). This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
Humanized mice (ie, PPARalpha-null mice transfected with human PPAR alpha) also fail to respond with hepatocellular and peroxisomal proliferation to fibrates, indicating that the human receptor cannot signal for proliferation.
Humans do not respond with hepatocellular and peroxisomal proliferation to fibrates and express PPARalpha at low levels and often in nonfunctional forms. Casarett & Doull's Toxicology: The Basic Science of Poisons, Eighth Edition
peroxisomal proliferation in hepatocyte [Eosinophilic granular degeneration]
hyperfunction of phenobarbital metabolism is a subtype of hyperfunctioning of drug metabolism: A process that performs an excessive phenobarbital metabolism. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
hyperfunction of phenobarbital metabolism [Ground glass appearance]
Peroxisomal Acox biosynthetic process is a subtype of protein production: A process that makes existent of a Peroxisomal acyl -coenzyme A oxidase (ACOX) due to biosynthesis or secretion resulting in an increase in its levels.
Organelle proliferation is a subtype of increasing number of objects: A process that becomes larger in the number of organelles.
The directed movement of long-chain fatty acids into a peroxisome. A long-chain fatty acid is a fatty acid with a chain length between C13 and C22. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
long-chain fatty acid import into peroxisome [Eosinophilic granular degeneration]
Peroxisomal Acox biosynthetic process is a subtype of protein production: A process that makes existent of a Peroxisomal acyl -coenzyme A oxidase (ACOX) due to biosynthesis or secretion resulting in an increase in its levels. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
peroxisomal Acox biosynthetic process [Eosinophilic granular degeneration]
Molecule transport is a subtype of transport: A process of the directed movement of molecules into, out of or within a cell, or between cells, or within a multicellular organism by means of some agent such as a transporter or pore..
A metabolic process by which 3-methyl branched fatty acids are degraded. These compounds are not degraded by the normal peroxisomal beta-oxidation pathway, because the 3-methyl blocks the dehydrogenation of the hydroxyl group by hydroxyacyl-CoA dehydrogenase. The 3-methyl branched fatty acid is converted in several steps to pristenic acid, which can then feed into the beta-oxidative pathway.
Controlling is a subtype of meta-function of "ToControl". When a function fa regularizes the behavior of ft, its meta-function is said to be 'to control ft'.
Phosphoethanolamine catabolic process is a subtype of catabolic process: A process of the chemical reactions resulting in the breakdown of phosphoethanolamine.
Negative regulation of decomposing is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of decomposing.
Any process that modulates the frequency, rate or extent of the chemical reactions and pathways involving lipids. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
regulation of lipid metabolic process [Eosinophilic granular degeneration]
Drug metabolism phase I by Cytochrome P450 is a subtype of drug metabolism phase I: A process that is biotransformed by cytochrome P450 (CYP) superfamily . This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
xenobiotic metabolism phase I by CyP [Glutathione depletion]
xenobiotic metabolism phase I by P450 [Glutathione depletion]
drug metabolism phase I by Cytochrome P450 [Glutathione depletion]
Regulation of beta oxidation related gene expression is a subtype of regulation of gene expression: A process that modulates the frequency, rate or extent of fatty acid beta oxidation related gene expression. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
regulation of beta oxidation related gene expression [Eosinophilic granular degeneration]
Regulation of beta oxidation related gene expression is a subtype of regulation of gene expression: A process that modulates the frequency, rate or extent of fatty acid beta oxidation related gene expression.
regulation of beta oxidation related gene expression
phosphatidylcholine + H2O = 2-acylglycerophosphocholine + a carboxylate.
fibrate [Eosinophilic granular degeneration]
Pirinixic Acid is a synthetic thiacetic acid derivative used in biomedical research, carcinogenic Pirinixic acid is a peroxisome proliferator that activates specific peroxisome proliferator-activated receptors (PPAR). PPARs play an important role in diverse cellular functions, including lipid metabolism, cell proliferation, differentiation, adipogenesis, and inflammatory signaling. (NCI04). Pirinixic Acid was discovered as WY-14,643 in 1974.
WY14643 [Eosinophilic granular degeneration]
16434500 Wy-14,643 (WY) is a hypolipidemic drug that induces hepatic peroxisome proliferation and tumors in rodents. Treatment with DEN + WY increased both cell proliferation and apoptosis in both the wild-type and p50 -/- mice; DEN treatment alone has no effect. In the DEN/WY-treated mice, cell proliferation and apoptosis were slightly lower in the p50 -/- mice than in the wild-type mice. These data demonstrate that NF-kappaB is involved in the promotion of hepatic tumors by the peroxisome proliferator WY; however, the difference in tumor incidence could not be attributed to alterations in either cell proliferation or apoptosis.
Receiving abnormal protein signal by PERK is a subtype of receiving signal: A process that recognizes another object and changes into an abnormal protein (e.g., misfolded protein, etc.) signal by PERK. This process is dependent on the translation attenuation and can constitute the course of ER stress.
receiving abnormal protein signal by PERK [ER stress - translation attenuation]
Transcription factor activation is a subtype of molecular activation: A process that changes the activity of the molecule with a transcription factor role to be higher.
PPARalpha activation is a subtype of activating nuclear receptor: A process that changes the activity of the activating PPAR alpha (Peroxisome Proliferator Activated Receptor Alpha) with a nuclear receptor role to be higher. The degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
PPARalpha activation (severe) [Eosinophilic granular degeneration]
PPARalpha: energy combustion, hypolipidemia, inflammation and cancer.
Negative regulation of mRNA catabolic process is a subtype of negative regulation of decomposing: Any process that stops, prevents or reduces the frequency, rate or extent of mRNA catabolic process.
down regulation of mRNA catabolic process
negative regulation of mRNA catabolic process
The cellular catabolic process in which cells digest parts of their own cytoplasm; allows for both recycling of macromolecular constituents under conditions of cellular stress and remodeling the intracellular structure for cell differentiation This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
autophagy [Eosinophilic granular degeneration]
Peroxisome proliferator-activated receptor α activation attenuates the inflammatory response to protect the liver from acute failure by promoting the autophagy pathway
Regulation of mitochondrial beta oxidation related gene is a subtype of regulation of beta oxidation related gene expression: A process that modulates the frequency, rate or extent of mitochondrial fatty acid beta oxidation related gene expression. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
regulation of mitochondrial beta oxidation related gene [Eosinophilic granular degeneration]
Regulation of mitochondrial beta oxidation related gene is a subtype of regulation of beta oxidation related gene expression: A process that modulates the frequency, rate or extent of mitochondrial fatty acid beta oxidation related gene expression.
regulation of mitochondrial beta oxidation related gene
Any process that decreases the rate, frequency or extent of lipid storage. Lipid storage is the accumulation and maintenance in cells or tissues of lipids, compounds soluble in organic solvents but insoluble or sparingly soluble in aqueous solvents. Lipid reserves can be accumulated during early developmental stages for mobilization and utilization at later stages of development. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
negative regulation of lipid storage [Eosinophilic granular degeneration]
Lipid transport to mitochondria is a subtype of lipid transport: A process that of the directed movement of lipids into a mitochondrion.
Unfolded protein is a subtype of substance with role. This entity can participate in a unfolded protein response in the course of ER stress.
Maintaining membrane permeability is a subtype of maintaining permeability: A process that keeps the permeability of the membrane.
Biological structure formation is a subtype of having extra parts: A process that changes to form a structure component.
A pathologic process that involves the transformation of normal cells to a neoplastic state and resulting in polyclonal or monoclonal neoplastic cell proliferation. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
tumorigenesis [Eosinophilic granular degeneration]
PPARα mediates the hepatocarcinogenic effect of certain peroxisome proliferators in rodents. However, no carcinogenic effect of peroxisome proliferators has been found in humans, possibly because expression of PPARα is much lower in human liver than in rodent liver or due to other species-specific differences.
Decreased expression of peroxisome proliferator-activated receptor alpha indicates unfavorable outcomes in hepatocellular carcinoma.
GADD45A (canonical)[Glutathione depletion]
Increasing size is a subtype of changing size: A process that changes the size of the object to be larger.
A size change process in which the size is increasing.
Increasing volume is a subtype of increasing size: A process that changes the volume of the object to be higher.
Increasing area is a subtype of changing area: A process that changes the area of the object to be larger.
Increasing length is a subtype of changing length: A process that changes the length of the object to be higher.
Increasing cell volume is a changing process to change the volume of the cell to increase.
Increasing volume of mitochondria is a changing process to change the volume of the mitochondria to increase.
Increasing energy is a subtype of increasing quantity: A process that changes the amount of energy to be larger.
Function-related process is a process that related to the execution of a function, a metafunction, and the malfunction.
FBRL: A Function and Behavior Representation Language. Sasajima, M., Kitamura, Y., Ikeda, M. & Mizoguchi, R., In Proc. of IJCAI-95 (pp. 1830-1836), 1995
This tree is based on a functional concept ontology (Kitamura 2002).
An ontology-based annotation framework for representing the functionality of engineering devices. Kitamura, Y., Washio, N., Koji, Y., Sasajima, M., Takafuji, S., & Mizoguchi, R., In Proc. of ASME 2006 International Design Engineering Technical Conferences & Computers and Information in Engineering Conference (ASME IDETC/CIE 2006), DETC2006-99131, 2006.
A functional concept ontology and its application to automatic identification of functional structures, Kitamura, Y., Sano, T., Namba, K., & Mizoguchi, R., Advanced Engineering Informatics, 16(2),145-163, 2002
Hyperfunction of mitochondrial fatty acid beta-oxidation is a subtype of hyperfunction of fatty acid beta-oxidation: A process that performs an excessive mitochondrial fatty acid beta-oxidation. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
hyperfunction of mitochondrial fatty acid beta-oxidation [Eosinophilic granular degeneration]
Refolding-unfolding imbalance is a subtype of imbalance: A process that lacks a balance between protein refolding and unfolding. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
refolding-unfolding imbalance [ER stress]
Massive hepatic necrosis is a subtype of classification of cell death by distribution: A hepatocyte necrosis localized around multiple lobules.
Any process that modulates the frequency, rate or extent of the chemical reactions and pathways involving carbohydrates. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
regulation of carbohydrate metabolic process [Eosinophilic granular degeneration]
Increasing energy is a subtype of increasing quantity: A process that changes the amount of energy to be larger. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
increasing energy [Eosinophilic granular degeneration]
TIMP1 production is a subtype of protein production: A process that makes existent of a TIMP1 protein due to biosynthesis or secretion resulting in an increase in its levels.
The chemical reactions and pathways resulting in the breakdown of a carbohydrate into pyruvate, with the concomitant production of a small amount of ATP and the reduction of NAD(P) to NAD(P)H. Glycolysis begins with the metabolism of a carbohydrate to generate products that can enter the pathway and ends with the production of pyruvate. Pyruvate may be converted to acetyl-coenzyme A, ethanol, lactate, or other small molecules. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
glycolytic process [Eosinophilic granular degeneration]
A role played by the entity that serves as an electron acceptor and electron donor in an electron transport chain. An electron transport chain is a process in which a series of electron carriers operate together to transfer electrons from donors to any of several different terminal electron acceptors to generate a transmembrane electrochemical gradient.
A role played by the entity that causes blood cells to grow and mature (Haematopoiesis).
Inflammatory cell infiltration is a subtype of moving A to the inside of B: A process that that moves the outside inflammatory cell to the inside in response to an inflammatory reaction. This entity is a specific course dependent process. This process can constitute the course of Phospholipidosis.
inflammatory cell infiltration [Phospholipidosis]
Decreasing sensitivity is a subtype of changing sensitivity: A process that changes the sensitivity to be lower.
Nuclear receptor activation is a subtype of activation of transcription factor: A process that changes the activity of the molecule with a nuclear receptor role to be higher.
Peroxisome Proliferator-Activated Receptor Gamma
Release of phospholipid from lysosome is a subtype of moving A to the outside of B: A process that that moves phospholipids to the outside of the lysosome.
Increasing hepatocellular volume is a subtype of increasing cell volume to change the volume of the hepatocyte to increase.
Increasing hepatocellular volume is a changing process to change the volume of the hepatocyte to increase. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
increasing hepatocellular volume [Eosinophilic granular degeneration]
Peroxisomes tylically occupy less than 2% of the cytoplasmic volume, while tratment with fibrate drugs inceases this volume to as much as 25%. Toxicity of Peroxisome Proliferators Molecular and Cellular Aspects of Toxicology John P. Vanden Heuvel
Addition of foreign substance is a subtype of assembling: A process that foreign substance to make an addition.
Dysfunction of calcium transport is a subtype of dysfunctioning: A process that performs an abnormal and incomplete calcium transport.
Having extra parts is a subtype of changing structure: A process that changes to have additional parts of the structure.
Accumulation of xenobiotics is a subtype of accumulation of substances in a biological object: A process that keeps xenobiotics in an organism, tissue, organelle, or cell.
Accumulation of compound in ER is a subtype of accumulation of xenobiotics: A process that keeps compound in the ER (endoplasmic reticulum). This entity is a specific course-dependent process. This process can constitute the course of ER stress.
accumulation of compound in ER [ER stress]
A role played by the role which catalyse the joining of two molecules with concomitant hydrolysis of the diphosphate bond in ATP or a similar triphosphate.
A role played by a chemical substance that reacts with the endogenous target molecule or critically alters the biological environment, initiating structural/functional alternations that result in toxicity.
Drug metabolism phase I is a subtype of drug metabolic process: A process that of biotransformation reactions involving hydrolysis, reduction, and oxidation or introduces a functional group (such as -OH, -NH2, -SH or -COOH) to increase in the water solubility of a xenobiotic.
Functionalization of exogenous substances to prepare them for conjugation in PHASE II DETOXIFICATION. Phase I enzymes include CYTOCHROME P450 enzymes and some OXIDOREDUCTASES. Excess induction of phase I over phase II detoxification leads to higher levels of FREE RADICALS that can induce CANCER and other cell damage. Induction or antagonism of phase I detoxication is the basis of a number of DRUG INTERACTIONS. MeSH:D050216
Phase 1 of metabolism is concerned with functionalization, that is the introduction or exposure of functional groups on the chemical structure of a compound. This provides a 'handle' for phase 2 conjugating species with which to react with. Many xenobiotics are lipophilic and almost chemically inert (e.g. PAHs) so would not necessarily undergo a phase 2 reaction. Making them more chemically reactive would facilitate their excretion but also increases their chance of reacting with cellular macromolecules (e.g. proteins, DNA). There is a fine balance between producing a more reactive metabolite and conjugation reactions. There are two groups of enzymes in phase 1 - oxidoreductases and hydrolases. Oxidoreductases introduce an oxygen atom into or remove electrons from their substrates. The major oxidoreductase enzyme system is called the P450 monooxygenases. Other systems include flavin-containing monooxygenases (FMO), cyclooxygenases (COX) and monoamine oxidases (MAO). Hydrolases hydrolyse esters, amides, epoxides and glucuronides.
Phase 1 - Functionalization of compounds (Homo sapiens)
Peroxisome fatty acid beta oxidation gene expression is a subtype of gene expression: A process that The process in which a gene sequence is converted into a mature peroxisome fatty acid beta oxidation gene product or products (proteins or RNA) . This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
peroxisome fatty acid beta oxidation gene expression [Eosinophilic granular degeneration]
Peroxisome fatty acid beta oxidation gene expression is a subtype of gene expression: A process that The process in which a gene sequence is converted into a mature peroxisome fatty acid beta oxidation gene product or products (proteins or RNA) .
peroxisome fatty acid beta oxidation gene expression
Hyperfunction of peroxisomal fatty acid beta-oxidation is a subtype of hyperfunction of fatty acid beta-oxidation: A process that performs an excessive peroxisomal fatty acid beta-oxidation. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
hyperfunction of peroxisomal fatty acid beta-oxidation [Eosinophilic granular degeneration]
Hyperfunction of peroxisomal fatty acid beta-oxidation is a subtype of hyperfunction of fatty acid beta-oxidation: A process that performs an excessive peroxisomal fatty acid beta-oxidation.
hyperfunction of peroxisomal fatty acid beta-oxidation
Increasing demand for peroxisomal fatty acid beta oxidation is a subtype of increasing functional demand: A process that changes the functional demand for peroxisomal fatty acid beta oxidation to be higher. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
increasing demand for peroxisomal fatty acid beta oxidation [Eosinophilic granular degeneration]
Increasing demand for peroxisomal fatty acid beta oxidation is a subtype of increasing functional demand: A process that changes the functional demand for peroxisomal fatty acid beta oxidation to be higher.
increasing demand for peroxisomal fatty acid beta oxidation
Accumulation of drug in hepatocyte is a subtype of accumulation of xenobiotics: A process that keeps compound in the hepatocyte. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
accumulation of drug in hepatocyte [Ground glass appearance]
Any process that stops, prevents, or reduces the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of lipids. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
negative regulation of lipid biosynthetic process [Eosinophilic granular degeneration]
Regulation of cell cycle related gene expression is a subtype of regulation of gene expression: A process that modulates the frequency, rate or extent of cel cycle related gene expression.
regulation of cell cycle related gene expression
Regulation of cell cycle related gene expression is a subtype of regulation of gene expression: A process that modulates the frequency, rate or extent of cel cycle related gene expression. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
regulation of cell cycle related gene expression [Eosinophilic granular degeneration]
Role of peroxisome proliferator-activated receptor alpha in altered cell cycle regulation in mouse liver: mRNAs encoding CDK-1, CDK-4, cyclin D1 and c-myc were also increased in wild-type mice fed Wy-14,643 but not in PPARalpha-null mice.
Biochemical degradation is a subtype of decompoing: A process that biochemically decomposes a single chemical entity into multiple element
A role played by the protein related to the microtubules of the cytoskeleton.
The chemical reactions and pathways resulting in the breakdown of lipids, compounds soluble in an organic solvent but not, or sparingly, in an aqueous solvent. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
lipid catabolic process [Eosinophilic granular degeneration]
SPON2(mouse) - obesity inhibitor[Phospholipidosis]
A role played by the entity that ihibits the obesity.
Negative regulation of cytokine gene expression is a subtype of negative regulation of gene expression: A process that stops, prevents, or reduces the frequency, rate or extent of inflammatory cytokine gene expression. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
negative regulation of cytokine gene expression [Eosinophilic granular degeneration]
Inflammatory cytokine gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature inflammatory cytokine gene product or products (proteins or RNA). This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
PPARα inhibits NF-κB to express inflammatory cytokines (TNF-α, IL-1b, etc).
inflammatory cytokine gene expression [Eosinophilic granular degeneration]
Inflammatory response is a subtype of changing material: The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages.
GSH is synthesized by two successive enzymatic reactions (Fig. 1). The first reaction, catalyzed by glutamate cysteine ligase (GCL), couples L-glutamate to L-cysteine to form γ-glutamylcysteine (γ-GC) .
Accumulation of abnormal proteins in ER is a subtype of accumulation of abnormal proteins: A process that keeps abnormal protein(s) in the ER (endoplasmic reticulum). This entity is a specific course-dependent process. This process can constitute the course of ER stress.
accumulation of abnormal proteins in ER [ER stress]
Any process that modulates the frequency, rate or extent of gene expression by miRNA.
Any process that modulates the frequency, rate or extent of gene expression by miRNA. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
regulation of gene expression by miRNA [Eosinophilic granular degeneration]
Oncogene mRNA stabilization is a subtype of keeping structure: A process that maintaing the mRNA structure of ongogenes.
Oncogene mRNA stabilization is a subtype of keeping structure: A process that maintaing the mRNA structure of ongogenes. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
oncogene mRNA stabilization [Eosinophilic granular degeneration]
Liver cacer dependent chemical entity is a subtype of toxic course dependent chemical entity. This entity can participate in the course of liver cancer.
Phospholipid transport from lysosome is a subtype of phospholipid transfer : A process of the transfer of a phospholipid from the lysosome. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
phospholipid transport from lysosome into cytosol [Phospholipidosis]
An inorganic radical in which a free electron resides on one or more oxygen atoms of an oxygen species.
Liver dysfunction is a subtype of dysfunctioning: A process that performs an abnormal and incomplete liver function.
The cellular catabolic process in which cells digest parts of their own cytoplasm; allows for both recycling of macromolecular constituents under conditions of cellular stress and remodeling the intracellular structure for cell differentiation. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Redox-active reactant formation is a subtype of biosynthetic process: A process that that generates a redox-active reactant.
A number of xenobiotics exert a toxic effect theough their metabolites. The increased reactivity may be due to conversion into electrophiles, free radicals, nucleophiles, or redox-active reactants. Casarett and Doull's toxicology 8th ed. Chapter 3 step1 Delibery:From the site to exposure to the target
Liver dysfunction is a subtype of dysfunctioning: A process that performs an abnormal and incomplete liver function. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Dysfunction of sodium transport is a subtype of dysfunctioning: A process that performs an abnormal and incomplete sodium transport
Dysfunction of generating protein is a subtype of dysfunctioning: A process that performs an abnormal and incomplete generating protein.
Free radicals formation is a subtype of biosynthetic process: A process that that generates a free radical, a highly reactive molecule with an unsatisfied electron valence pair.
Nucleophiles formation is a subtype of biosynthetic process: The chemical reaction resulting in the formation of nucleophiles by donating electrons.
Nucleophiles generally are detoxificated by conjugation of a functinal group to the nucleophilic atom. Sulfonation, glucuronidation, methylation, and acetylation are common reactions.
IL-2 gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature IL-2 gene product or products (proteins or RNA).
Electrophiles formation is a subtype of biosynthetic process: A process that that generates electrophiles. Electrophile is a reagent that forms a bond to its reaction partner (the nucleophile) by accepting both bonding electrons from that reaction partner..
A number of xenobiotics exert a toxic effect theough their metabolites. Electrophiles are molecules that contain an electron-deficient atom with a partial or full positive charge that can react by sharing electron pairs with electron rich atoms in nucleophiles. Electrophilic toxicants generally are detoxificated by conjugation of with the nucleophile, glutathione. This reaction can be facilitated by glutathione S-trasferases.
Protein quality control for misfolded or incompletely synthesized proteins is a subtype of keeping quality: A process that maintains the protein quality.
protein quality control for misfolded or incompletely synthesized proteins
GO:0006515 (protein quality control for misfolded or incompletely synthesized proteins) focuses on ERAD process. Our entity includes the process such as protein folding, ERAD and translation attenuation for unfolded protein response.
protein quality control for unfolded proteins
Protein quality control for misfolded or incompletely synthesized proteins is a subtype of keeping quality: A process that maintains the protein quality mediated by the gene expression regulation. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
protein quality control for unfolded via gene expression regulation [ER stress]
Dysfunction of protein quality control is a subtype of dysfunctioning: A process that performs an abnormal and incomplete protein quality control function.
Increasing number of stress responses is a subtype of increasing number of actions: A process that becomes larger in the number of stress responses.
A process that results in an increase in hepatic cell number by cell division, often leading to an increase in the size of an liver. This entity is a specific course-dependent process. This process can constitute the course of Hypertrophy.
Icreasing volume of endoplasmic reticulum is a subtype of increasing organelle volume: A process that changes the volume of the endoplasmic reticulum to be higher.
icreasing volume of endoplasmic reticulum
Fibrosis is a subtype of changing material: A process that replaces tissues to fibrous connective tissues/
Deacreasing size is a subtype of changing size: A process that changes the size of the object to be smaller.
Hepatocellular atrophy is a subtype of decreasing volume: A process that changes the volume of the hepatocyte to be relatively low.
Damaging is a subtype of changing structure: A process that injuries the structure as the direct or indirect result of an external force.
injury http://purl.obolibrary.org/obo/OGMS_0000102
Drug-, radiation-induced, or spontaneous injuries to DNA that introduce deviations from its normal double-helical conformation. These changes include structural distortions that interfere with replication and transcription, as well as point mutations that disrupt base pairs and exert damaging effects on future generations through changes in DNA sequence. If the damage is minor, it can often be repaired (DNA repair); extensive damage can induce apoptosis. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
TIMP1 production is a subtype of protein production: A process that makes existent of a TIMP1 protein due to biosynthesis or secretion resulting in an increase in its levels. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
Cellular damage is a subtype of damaging: A process that injuries the structure of the cell as the direct or indirect result of an external force.
Cell damage (also known as cell injury) is a variety or changes of stress that a cell suffers due to external as well internal environmental changes. Among other causes, this can be due to physical, chemical, infectious, biological, nutritional or immunological factors. Cell damage can be reversible or irreversible. Depending on the extent of injury, the cellular response may be adaptive and where possible, homeostasis is restored. Cell death occurs when the severity of the injury exceeds the cell’s ability to repair itself. Cell death is relative to both the length of exposure to a harmful stimulus and the severity of the damage caused. Cell death may occur by necrosis or apoptosis.
Cellular damage is a subtype of damaging: A process that injuries the structure of the cell as the direct or indirect result of an external force. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
Cytoskeleton damage is a subtype of cellular damage: A process that injuries the structure of the cytoskeleton as the direct or indirect result of an external force.
Six proteins were regulated at both basal and inducible levels exhibiting the largest dynamic range of Nrf2 regulation: cytochrome P4502A5 (CYP2A5; 17.2-fold), glutathione-S-transferase-Mu 3 (GSTM3; 6.4-fold), glutathione-S-transferase Mu 1 (GSTM1; 5.9-fold), ectonucleoside-triphosphate diphosphohydrolase (ENTPD5; 4.6-fold), UDP-glucose-6-dehydrogenase (UDPGDH; 4.1-fold) and epoxide hydrolase (EPHX1; 3.0-fold). These proteins, or their products, thus provide a potential source of biomarkers for Nrf2 activity.
GSTM3 (canonical)[Glutathione depletion]
Coordinated regulation of hepatic phase I and II drug-metabolizing genes and transporters using AhR-, CAR-, PXR-, PPARα-, and Nrf2-null mice.
GSTM3 overexpression sensitized the PLC/PRF/5R cells to radiation mainly though induction of apoptosis. GSTM3 increased the expression of cell cycle- and apoptosis-related genes (Bcl-2, Bax, p21, p27 and p53) in PRF/PLC/5R cells with irradiation
GSTA3 (canonical)[Glutathione depletion]
Gene expression by AP-1 is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) by AP-1.
The assembly of a bleb, a cell extension caused by localized decoupling of the cytoskeleton from the plasma membrane and characterized by rapid formation, rounded shape, and scarcity of organelles within the protrusion. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
Increasing membrane permeabilization is a subtype of changing permeability: A process that changes the permeability of the membrane to be higher.
Any process that increases the frequency, rate or extent of the passage or uptake of molecules by the mitochondrial membrane. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
positive regulation of mitochondrial membrane permeability [Phospholipidosis]
Any process that increases the frequency, rate or extent of the passage or uptake of molecules by the mitochondrial membrane. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
positive regulation of mitochondrial membrane permeability [Cell death]
positive regulation of mitochondrial membrane permeability involved in apoptotic process
Dysregulation of apoptosis is a subtype of malfunctioning of controlling: A process that cannot perform a regulation of apoptotic process appropriately or cannot realize it at all.
A pathologic process that involves the transformation of normal cells to a neoplastic state and resulting in polyclonal or monoclonal neoplastic cell proliferation. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
Gene expression by p53 is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) by XBP1.
Changing cytoskeleton is a subtype of changing structure: A process that changes the structure of cytoskeleton.
Changing cytoskeleton is a subtype of changing structure: A process that changes the structure of cytoskeleton. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
Hypofunction of keeping structure is a subtype of hypofunctioning: A process that performs a decreased or insufficient keeping structure.
Hypofunction of keeping structure is a subtype of hypofunctioning: A process that performs a decreased or insufficient keeping structure. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
hypofunction of keeping structure [Cell death]
Decreasing area is a subtype of changing area: A process that changes the area of the object to be smaller.
Decreasing volume is a subtype of changing volume: A process that changes the volume of the object to be relatively low
Decreasing length is a subtype of changing length: A process that changes the length of the object to be lower.
Decreasing contact area with ECM is a subtype of decreasing area: A process that changes the contact area with extracellular matrix (ECM) to be smaller.
Decreasing contact area with ECM is a subtype of decreasing area: A process that changes the contact area with extracellular matrix (ECM) to be smaller. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
decreasing contact area with ECM [Cell death]
Accumulation of substances in a biological object is a subtype of storing: A process that keeps substances in an organism, tissue, organelle, or cell.
related quality http://purl.obolibrary.org/obo/PATO_0002269
accumulation of substances in a biological object
Protein accumulation is a subtype of accumulation of substances in a biological object: A process that keeps protein(s) in a biological object.
Increasing sensitivity is a subtype of changing sensitivity: A process that changes the sensitivity to be lhigher.
Accumulation of abnormal proteins in ER is a subtype of accumulation of abnormal proteins: A process that keeps abnormal protein(s) in the ER (endoplasmic reticulum). And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of ER stress (severe) .
accumulation of abnormal proteins in ER [ER stress (severe) ]
Accumulation of abnormal proteins is a subtype of protein accumulation: A process that keeps abnormal protein(s) in a biological object.
Mitochondrial dysfunction is a subtype of dysfunctioning: A process that performs an abnormal and incomplete mitochondrial function. This entity is a specific course-dependent process. This process can constitute the course of cell death.
Increasing size of liver is a subtype of increasing size: A process that changes the size of the liver to be larger.
Vitamine accumulation is a subtype of accumulation of substances in a biological object: A process that keeps vitamin in a biological object.
Accumulation of protein aggregates is a subtype of protein accumulation: A process that keeps protein aggregates in a biological object.
Protein aggretates are often insoluble and tend to sequester Fe 2+ ions. Fe 2+ helps to produce ROS.
Fatty acid strorage is a subtype of accumulation of substances in a biological object: A process that keeps fatty acid in a biological object.
Substance with stress sensor role is a subtype of substance with role. This entity is participating in a stress response and playing a stress sensor role.
Melanin deposition is a subtype of accumulation of pigments: The aggregation of melanin in a particular location in an organism, tissue or cell.
Lipofuscin deposition is a subtype of accumulation of pigments: The aggregation of lipofuscin in a particular location in an organism, tissue or cell.
Substance with apoptosis inducer role is a subtype of substance with role. This entity is participating in a positive regulation of apoptosis process and playing an apoptosis inducer role.
Changing relationship between operands is a subtype of changing: A process that changing the relationship between multiple objects.
The totality of all processes through which ATP depltion is realized.
Bile acid strorage is a subtype of accumulation of substances in a biological object: A process that keeps bile acid within the liver (intrahepatic), or outside the liver (extrahepatic) in the bile duct system.
Bile acid accumulation in hepatocyte is a subtype of accumulation of substances in a biological object: A process that keeps bile acid within the hepatocute in the liver (intrahepatic). This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
bile acid accumulation in hepatocyte [Cholestasis]
Increasing hepatocellular volume is a changing process to change the volume of the hepatocyte to increase. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
increasing hepatocellular volume [Cholestasis]
A role played by the entity that catalyses the transfer of ubiquitin to a substrate protein via the reaction X-ubiquitin + S -> X + S-ubiquitin, where X is either an E2 or E3 enzyme, the X-ubiquitin linkage is a thioester bond, and the S-ubiquitin linkage is an amide bond: an isopeptide bond between the C-terminal glycine of ubiquitin and the epsilon-amino group of lysine residues in the substrate or, in the linear extension of ubiquitin chains, a peptide bond the between the C-terminal glycine and N-terminal methionine of ubiquitin residues.
Increasing amount of carbohydrate is a subtype of increasing quantity: A process that changes the amount of carbohydrates to be higher.
Bile acid biosynthetic process is a subtype of biosynthetic process: The chemical reactions resulting in the formation of bile acids, any of a group of steroid carboxylic acids occurring in bile. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
bile acid biosynthetic process [Cholestasis]
Bile acid transport to hepatocyte is a subtype of bile acid and bile salt transport: A process that transports bile acid within a hepatocyte by means of some agent such as a transporter or pore.
Location-independent. State corresponds not to generic quality but to property. It is possessed by continuants and processes.
Primitive process is a unit of process. Process series at a certain granular level can appear as one primitive process at the higher level.
Whether the process is a primitive process or not depends on the setting of the granularity. When one does not consider the details more than a certain level, or a level as the minimum grain size, the process at that level becomes the primitive process.
OATPs have a preference for unconjugated bile acids over conjugated bile salts
organic anion transporting polypeptides [Cholestasis]
glibenclamide is a potential substrate for OATPs.
Cholestasis dependent chemical entity is a subtype of toxic course dependent chemical entity. This entity can participate in the course of cholestasis.
PERK signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the PERK. PERK generally plays a endoplasmic reticulum membrane stress sensor role.
Value of quality. Although this is essentially a role played by quantity, YAMATO doesn't deal with it so for simplicity.
Cholestasis dependent gene is a subtype of toxic course dependent chemical entity. This gene can participate in the course of cholestasis as a gene product. Gene profile:caonical that described in textbooks or articles.
cholestasis dependent molecule (canonical)
This is essentially a value and non-quantitative, therefore, there is no ordering among values, unlike non-categorial values. Categorical quality has typicality which no quantity has. It is generically dependent on entity because it is always referred to with something as a species.
It is just a quantity independent of what quantity it is of. That is, 10cm and 11cm exist just as it is in the quantity space and are just different. On the other hand, when a thing's length is 10cm long at time t1 and 11cm long at t2, we say the length of the thing CHANGED. The 10cm long of a thing has its identity which persists having possibly different values. Note that quantity is not specifically dependent on anything, but generically dependent on physical entity.
Dysfunction of fatty acid degradation is a subtype of hypofunctioning: A process that performs a decreased or insufficient lipid degradation. This entity is a specific course-dependent process. This process can constitute the course of Alcoholic fatty liver.
dysfunction of fatty acid degradation [Alcoholic fatty liver]
Tumor cell survial is a subtype of cell survival: A process that keeps the viability of a tumor cell.
Phospholipid accumulation in lysosome is a subtype of phospholipid accumulation: A process that keeps phospholipid in the lysosome.
Converting to acetyl CoA is a subtype of metabolic process that transforms into acetyl CoA.
Increasing fatty acid synthesis substrate is a subtype of increasing quantity: A process that changes the production amount of the substrate of the fatty acid synthesis.
Increaseing fatty acid synthesis substrate
A series of molecular signals mediated by PERK (PKR-like ER kinase).
A value which is greater than the normal or average.
A qualitative value which is lower than the threshold, normal or average.
Although these are qualitative values, they are essentially quantitative because they are derived from the quantitative values by introducing threshold value, and hence the values are ordinal.
Times quality value is a subtype of meta attribute value.
Acute phase proteins coding gene expression via cytokine is a subtype of gene expression: A process that The process in which a gene sequence is converted into a mature acute phase proteins coding gene product or products (proteins or RNA) by cytokine. Casarett & Doull's Toxicology: The Basic Science of Poisons, Eighth Edition
IL-1, TNF, IL-6 or other cytokines released from macrophages and endtherial cells act on cell surface receptors to change transcriptions of genes involving tissue injury and repair.
acute phase proteins coding gene expression via cytokine
Oxidative stress dependent chemical entity is a subtype of toxic course dependent chemical entity. This entity can participate in the course of ER stress.
別名BSEP。アミノ酸抱合胆汁酸の毛細胆管への排泄を行う。
Bosentan, cyclosporin, glibenclamide, rifampicin, and rifamycin inhibit human and rat BSEP/Bsep.
Cyclosporin A, rifamycin SV, rifampicin, and glibenclamide cis-inhibited Bsep-mediated bile salt transport to similar extents as ATP-dependent taurocholate transport in cLPM vesicles. The cholestatic estrogen metabolite estradiol-17beta-glucuronide inhibited ATP-dependent taurocholate transport only in normal canalicular plasma membrane and in Bsep/Mrp2-coexpressing Sf9 cell vesicles.
In isolated canalicular rat liver plasma membrane preparations, troglitazone competitively inhibited the ATP-dependent taurocholate transport mediated by the canalicular bile salt export pump (Bsep). Troglitazone sulfate, the main troglitazone metabolite eliminated into bile, also showed competitive Bsep inhibition.
This is an abstraction of the kinds at the class level. In the use case, it is sometimes referred to with # operator as a class constraint like "#generic quality". In a common term, it would be called "attribute". Its instance is not equal to its value. The value itself belongs to "quality value". Its instance is still an attribute which refers to a specific quantity. Its instnace plays a quality role like length plays one's height as a quality role. Quality such as one's height, one's weight, etc. are roles, and hence must be defined in the context of respective contexts(entities). Therefore, they are not defined as basic type like length, weight, etc. See "physical" in which a most generic quality is defined. Quality in DOLCE corresponds to quality role type in YAMATO. This is why "quality" is invisible in YAMATO in spite of it knows "quality".
PERK - stress sensor (canonical)[ER stress]
An attribute that counting numbers of objects and how many times an event happens are essential not to individuals in them but to collectives of objects or events.
not clock time but times (how many times). Contrary to the intuition, "times" should not be taken as a generic quality. What should be taken as a generic quality is the pai rof "event" and times. That is, "what event happens many times" corresponds to "color is red". For example, "A month which has many accidents" corresponds to "A rose whose color is red".
not numerals but "number" of somethings(=how many things)
Protein biosynthesis is a subtype of biosynthetic process:The chemical reactions resulting in the formation of proteins.
A role played by the entity which catalyses the cleavage of C-C, C-O, C-N and other bonds by other means than by hydrolysis or oxidation, or conversely adding a group to a double bond. They differ from other enzymes in that two substrates are involved in one reaction direction, but only one in the other direction. When acting on the single substrate, a molecule is eliminated and this generates either a new double bond or a new ring.
A 2-D extent attribute inhering in a bearer by virtue of the bearer's two dimensional extent.
Color as a kind is a generic quality. Red is a subclass of color and/or a value of color as discussed below, and being red is a property of things. The differentiation between red as a value of color and being red as a property is critical. In summary, there are three kinds of red. It is unary rather than binary just like ordinary classes such as animal, car, etc
Moving drug to the inside of liver is a subtype of moving A to the inside of B: A process that of the movement of drug into a liver.
A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died. This entity is a specific course-dependent process. This process can constitute the course of liver tumor via ground glass appearance.
apoptosis [liver tumor via ground glass appearance]
A color brightness which is relatively high.
Drug Chem Toxicol. 2005;28(1):117-33. Induction of apoptosis by cationic amphiphilic drugs amiodarone and imipramine. Treatment of U-937 cells with these compounds for 96 h resulted in concentration-related increases in phospholipids. Disruption of cell lysosomes in U-937 cells following accumulation of phospholipids does not cause a cell cycle arrest but instead induces apoptosis by activation of caspase pathways.
Amiodarone induces phospholipidosis Amiodarone inhibits PLA2. Amiodarone accumulates in the lysosome and insert into the inner membranbe decreasig the anionic binding site for the lipase. Lipase is not able to bind to phopholipid and to be degraded by lysosomal proteases. Biochim Biophys Acta. 2013 Mar; 1831(3): 602–611.
Treating both B-13 and B-13/H cells with the drug amiodarone, which has been reported to induce phospholipidosis in variety of cell types, induced phospholipidosis most markedly in B-13/H cells.
Cationic amphiphilic drug-induced phospholipidosis.
gentamicin_sphingomyelinase inhibitor [Phospholipidosis]
Leupeptin and E-64, inhibitors of cysteine proteinases, prevent gentamicin-induced lysosomal phospholipidosis in cultured rat fibroblasts.
tamoxifen phospholipase inhibitor[Phospholipidosis]
A role played by the entity which receives acute phase response signal and transmits operand(s).
Lamellar body formation in lysosome is a subtype of biological structure formation: A process that costructs lamellar body in lysosome.
The totality of all processes through which cell death is realized.
Classification of cell death recommendations of the Nomenclature Committee on Cell Death 2009
Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012
Apoptosis (course) is a subtype of cell death (course). The totality of all processes through which apoptosis is realized.
Increasing drug metabolite is a subtype of increasing quantity: A process that changes the amount of drug metabolites to be higher. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
increasing drug metabolite [Ground glass appearance]
Pyroptosis (course) is a subtype of cell death (course). The totality of all processes through which pyroptosis is realized.
Pyroptosis is related to a caspase-1-dependent cell death subroutine that is associated with the generation of pyrogenic mediators such as Il-1beta and Il-18.
The term pyroptosis has been introduced in 2000 by Brennan and Cookson to functionally describe the peculiar death of macrophages infected by Salmonella typhimurium. Several other bacterial triggers of this atypical cell death modality have been identified, including Shigella flexneri, Listeria monocytogenes, Pseudomonas aeruginosa, Francisella tularensis and the Bacillus anthracis. However, it has become clear that pyroptosis neither constitutes a macrophage-specific process nor a cell death subroutine that only results from bacterial infection. Of note, pyroptotic cells can exhibit apoptotic and/or necrotic morphological features.
Apoptosis modulator is a role played by any substance that regulates the process of apoptosis (programmed cell death) in multi-celled organisms.
A role played by the entity which enables the facilitated diffusion of an ion (by an energy-independent process) by passage through a transmembrane aqueous pore or channel without evidence for a carrier-mediated mechanism. May be either selective (it enables passage of a specific ion only) or non-selective (it enables passage of two or more ions of same charge but different size).
A role played by the entity that ihibits the activity of tumor cells.
A role that controls the rate, timing and/or magnitude of transcription of genetic information. The function of transcriptional regulators is to modulate gene expression at the transcription step so that they are expressed in the right cell at the right time and in the right amount throughout the life of the cell and the organism.
A role played by the entity which enables the transfer of a drug from one side of a membrane to the other. A drug is any naturally occurring or synthetic substance, other than a nutrient, that, when administered or applied to an organism, affects the structure or functioning of the organism; in particular, any such substance used in the diagnosis, prevention, or treatment of disease.
The totality of genetic information belonging to a cell or an organism; in particular, the DNA that carries this information.
Separating is a subtype of changing between operands: A process that divides the whole object into multiple components.
Hyperfunction of Kupffer cell differentiation is a subtype of hyperfunction of cell differentiation: A process that performs an excesssive kupffer cell differentiation. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense).
hyperfunction of Kupffer cell differentiation [Phospholipidosis (excessive defense)]
ATF6 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the ATF6 (activating transcription factor 6). ATF6 generally plays a endoplasmic reticulum membrane stress sensor role.
Amino acid conjugatied bile acid transport into bile canaliculus is a subtype of canalicular bile acid transport: A process that enables the transfer of amino acid conjugated bile acid from one side of a hepatocyte plasma membrane into a bile canaliculus.
amino acid conjugatied bile acid transport into bile canaliculus
Changing fluidity is a subtype of changing quality: A process that changes the fluidity of the object.
The multiplication or reproduction of cells, resulting in the rapid expansion of a cell population. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
Tumor cell proliferation is a subtype of cell proliferation: A process of the multiplication or reproduction of tumor cells, resulting in the rapid expansion of a tumor cell population.
Tumor cell proliferation is a subtype of cell proliferation: A process of the multiplication or reproduction of tumor cells, resulting in the rapid expansion of a tumor cell population. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
Increasing number of dead cells in liver is a subtype of increasing number of objects: A process that becomes larger in the number of dead cells in the liver.
increasing number of dead cells in liver
Increasing number of dead cells in liver is a subtype of cell proliferation: A process that becomes larger in the number of dead cells in the liver. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
increasing number of dead cells in liver [ER stress]
Decomposing is a subtype of separating: A process that divides a whole object into constituents.
Increasing number of action is a subtype of changing: A process that becomes larger in the number of actions or activities.
Increasing autodigestion of abnormal lysosome is a subtype of increasing autophagy: A process that becomes larger in the number of autodigestion of abnormal lysosome.
increasing autodigestion of abnormal lysosome
Hypofunction of ATP biosynthesis is a subtype of hypofunction of biosynthesis: A process that performs a decreased or insufficient ATP biosynthesis. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
hypofunction of ATP biosynthesis [cell death]
Increasing number of bile duct in liver is a subtype of increasing number of objects: A process that becomes larger in the number of bile duct in the liver.
Decreasing number of objects is a subtype of changing: A process that becomes smaller in number of physical objects.
Cleavage of ATF6-alpha by S2P is a subtype of proteolysis: A process n which ATF6-alpha is cleaved by endopeptidase S2P( MBTPS2). Site-2 cleavage comes after site-1 cleavage. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
cleavage of ATF6-alpha by S2P [ER stress]
Cholestasis (primitive process) is a subtype of stagnating: A process that changes the bile flow to be slower due to obstruction. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
Decreasing number of cells is a subtype of decreasing number of objects: A process that becomes smaller in number of cells.
Increasing concentration is a subtype of changing concentration: A process that changes the concentration of the object to be higher.
Increasing calcium ion concentration in blood is a subtype of increasing concentration: A process that changes the calcium ion concentration in the blood to be higher.
increasing calcium ion concentration in blood
Increase in intracellular calcium level is a subtype of increase in calcium level: A process that changes the calcium ion concentration within a cell to be higher.
Increase in intracellular calcium level is a subtype of increase in calcium level: A process that changes the calcium ion concentration within a cell to be higher. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
increase in intracellular calcium level [Cell death]
Amino acid conjugatied bile acid transport into bile canaliculus is a subtype of canalicular bile acid transport: A process that enables the transfer of amino acid conjugated bile acid from one side of a hepatocyte plasma membrane into a bile canaliculus. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
amino acid conjugatied bile acid transport into bile canaliculus [Cholestasis]
PERK activation is a subtype of Molecular activation: A process that changes the activity of PERK to be higher.
AMPK activation is a subtype of molecular activation: A process that changes the activity of the AMPK (AMP-activated protein kinase) to be higher. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Blocking autophagy by 3-methyladenine (3-MA) or Atg5 siRNA knock-down enhanced meloxicam lethality for HCC by activation of ER stress-related apoptosis. In addition, GRP78 seemed to lead to autophagic activation via the AMPK-mTOR signalling pathway. Blocking AMPK with a chemical inhibitor inhibited autophagy suggesting that meloxicam-regulated autophagy requires activation of AMPK. CONCLUSIONS: Our results revealed that both ER stress and autophagy were involved in cell death evoked by meloxicam in HCC cells. This inhibition of autophagy to enhance meloxicam lethality, suggests a novel therapeutic strategy against HCC.
Decreasing blood flow is a subtype of decreasing flow: A process that changes the blood flow to be smaller.
Oxidative stress dependent chemical compound is a subtype of toxic course dependent chemical entity. This entity (drug) can participate in the course of Oxidative stress.
Increasing demand for response to stress is a subtype of increasing functional demand: A process that changes the functional demand for the response to the stress to be higher.
increasing demand for response to stress
Increasing demand for response to ER stress is a subtype of increasing the demand for response to stress: A process that changes the functional demand for the response to the endoplasmic reticulum (ER) stress to be higher.
increasing demand for response to ER stress
Increasing demand for response to ER stress is a subtype of increasing the demand for response to stress: A process that changes the functional demand for the response to the edoplasmic reticulum (ER) stress to be higher. This entity is a specific course-dependent process. This process can constitute the course of ER stress (severe) .
increasing demand for response to ER stress [ER stress (severe) ]
Increaseing production quantity of ROS is a subtype of increasing quantity: A process that changes the production amount of reactive oxygen species, any molecules or ions formed by the incomplete one-electron reduction of oxygen, to be higher.
Increasing production quantity of RNS is a subtype of increasing quantity: A process that changes the production amount of reactive nitrogen species (RNS) to be higher
Increasing calcium ion is a subtype of increasing quantity: A process that changes the calcium ion becomes larger.
Increasing sodium ion inflow into cell is a subtype of increasing quantity: A process that changes the sodium ion inflow into the cell to be larger.
increasing extracellular potassium outflow is a subtype of increasing quantity: A process that changes the phospholipid inflow into the hepatocyte to be larger.
increasing extracellular potassium outflow
Negative regulation process is a subtype of controlling: A process that that stops, prevents, or reduces the frequency, rate or extent of function.
Controlling to the negative (-) direction.
Negative regulation of cell cycle G2/M phase transition is a subtype of negative regulation of cell cycle: Any process that stops, prevents or reduces the frequency, rate or extent of cell cycle G2/M phase transition.
negative regulation of cell cycle G2/M phase transition
Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process. This entity is a specific course-dependent process. This process can constitute the course of ER stress (mild).
negative regulation of apoptotic process [ER stress (mild)]
Drug metabolism phase I by Cytochrome P450 is a subtype of drug metabolism phase I: A process that is biotransformed by cytochrome P450 (CYP) superfamily . This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
drug metabolism phase I by Cytochrome P450 [Ground glass appearance]
Any process that modulates the rate or extent of progression through the cell cycle. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
The process in which a gene's sequence is converted into a mature gene product or products (proteins or RNA) by transcription factor
Gene expression by transcriptional regulator
Cell survial is a subtype of keeong quantity: A process that keeps the viability of a cell. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Cell survial is a subtype of keeong quantity: A process that keeps the viability of a cell. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
Functioning process is a subtype of function-related process: A process that executes and manifests function.
Receiving is a subtype of functioning process: A process that that gets an object as input.
Making existence is a subtype of functioning process: A process that makes a target object to be present in another object.
Generating is a subtype of funcioning: A process that produces output from nothing.
Protein production is a subtype of generating: A process that synthesizes protein (s) resulting in having output (s).
Abnormal protein-degrading enzyme production is a subtype of protein production: A process that makes existent of an abnormal protein-degrading enzyme protein due to biosynthesis or secretion resulting in an increase in its levels. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
abnormal protein-degrading enzyme production [ER stress]
Chaperon production is a subtype of protein production: A process that makes existent of a protein with a chaperon role due to biosynthesis or secretion resulting in an increase in its levels.
Abnormal protein-degrading enzyme production is a subtype of protein production: A process that makes existent of an abnormal protein-degrading enzyme protein due to biosynthesis or secretion resulting in an increase in its levels.
abnormal protein-degrading enzyme production
Any process that activates or increases the frequency, rate or extent of ERAD pathway. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Changing is a subtype of making existence: A process that makes a target object different.
PERK autophosphorylation is a subtype of protein autophosphorylation: The phosphorylation by PERK of one or more of its own amino acid residues (cis-autophosphorylation), or residues on PERK (trans-autophosphorylation). This process is dependent on the translation attenuation and can constitute the course of ER stress.
PERK autophosphorylation [ER stress - translation attenuation]
Converting signal to information is a subtype of converting to information: A process that changes a signal to information.
Converting signal to information is a subtype of converting to information: A process that changes a signal to information. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
converting signal to information [ER stress]
Converting signal to information is a subtype of converting to information: A process that changes a signal to information. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
converting signal to information [Cell death]
Changing an operand is a subtype of changing: A process that makes one object different.
Membrane phospholipid catabolic process is a subtype of lipid catabolic process: The chemical reactions resulting in the breakdown of membrane phopholipids
Changing quantity is a subtype of changing attribute: A process that changes the amount of the object as an output.
Increasing quantity is a subtype of changing quantity: A process that changes the magnitude of the object to be larger.
Decreasing quantity is a subtype of changing quantity: A process that changes the magnitude of the object to be smaller.
Decreasing production quantity of protein is a subtype of decreasing quantity: A process that changes the production quantity of the protein to be lower. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
decreasing production quantity of protein [ER stress]
Hyperfunction of hypoxia resonsive gene expression is a subtype of hyperfunction of gene expression: A process that performs an excesssive hypoxia resonsive gene expression.
hyperfunction of hypoxia resonsive gene expression
The process in which a gene's sequence is converted into a mature gene product or products (proteins or RNA). This includes the production of an RNA transcript as well as any processing to produce a mature RNA product or an mRNA or circRNA (for protein-coding genes) and the translation of that mRNA or circRNA into protein. Protein maturation is included when required to form an active form of a product from an inactive precursor form. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
Uncoupling dependent chemical entity is a subtype of toxic course dependent chemical entity. This entity can participate in the course of uncoupling of mitochondrial damage.
Activating is a subtype of changing activity: A process that changes the activity of the object to be higher.
PERK activation is a subtype of Molecular activation: A process that changes the activity of PERK to be higher. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
NRF2 activation by PERK is a subtype of NRF2 activation: A process that changes the activity of NRF2 (Nuclear Factor, Erythroid 2 Like 2) to be higher by PERK. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Mild ER stress activates Nrf2 and the antiapoptotic factor BI-1. Activation of Nrf2 through its phosphorylation by PERK,and BI-1 protect the endoplasmic reticulum from further damage by inhibiting the production of ROS by CYP2E1(Lee et al., 2007; Kim et al., 2009).
NRF2 activation by PERK [ER stress (mild)]
AMPK activation is a subtype of molecular activation: A process that changes the activity of the AMPK (AMP-activated protein kinase) to be higher.
Positive regulation of autophagy by AMPK is a subtype of positive regulation of autophagy: A process that that activates or increases the frequency, rate or extent of autophagy by AMPK.
positive regulation of autophagy by AMPK
GRP78 activation by MLX is a subtype of molecular activation: A process that changes the activity of the GRP78/ HSPA5 (Heat Shock Protein Family A (Hsp70) Member 5) to be higher by MLX.
PLA2 activation is a subtype of molecular activation: A process that changes the activity of the member of the phospholipase A2 family (PLA2) to be higher.
Protease activation is a subtype of molecular activation: A process that changes the activity of the molecule with a protease role to be higher.
Changing shape is a subtype of changing structure: A process that changes the form of the operand.
Liver X receptor activation is a subtype of activating nuclear receptor: A process that changes the activity of the activating LXR ( liver X receptor) with a nuclear receptor role to be higher.
Changing membrane fluidity is a subtype of changing fluidity: A process that changes the fluidity of the membrane.
Any process that activates or increases the frequency, rate or extent of protein refolding. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
positive regulation of protein refolding [ER stress]
Keeping quantity is a subtype of changing amount: A process that maintains the magnitude of the object at a constant level .
Changing quality is a subtype of changing an operand: A process that changes the quality of the object.
Negative regulation of formation of cytoplasmic translation initiation complex by eIF2a is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of formation of cytoplasmic translation initiation complex by eIF2a. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
negative regulation of formation of cytoplasmic translation initiation complex by eIF2a [ER stress]
Activated PERK phosphorylates the eIF2α at serine 51, resulting in inactivation of eIF2α, preventing assembly of the preinitiation ribosome complex. This attenuates general mRNA translation. ATF4 which has a subset of mRNAs with small upstream open reading frames or internal ribosome entry sites are translated.
Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase.
Changing volume is a subtype of changing quality: A process that changes the volume of the object.
Homeostatic imbalance of number of smooth endoplasmic reticulum is a subtype of imbalance: A process that becomes lacking a homeostastasis balance of the proliferation and elimination of smooth endoplasmic reticulum.
homeostatic imbalance of number of smooth endoplasmic reticulum
Keeps volume is a subtype of changing volume: A process that keeps the volume of the object.
Changing density is a subtype of changing quality: A process that changes the density of the object.
Changing hardness is a subtype of changing quality: A process that changes the hardness of the object.
Changing phase is a subtype of changing an operand: A process that changes the phase of the operand.
Solidifying is a subtype of changing phase: A process that changes the phase of the operand to a solid phase.
Vaporizing is a subtype of changing phase: A process that changes the phase of the operand to a vapor phase.
Liquefying is a subtype of changing phase: A process that changes the phase of the operand to a liquid phase.
Moving is a subtype of changing an operand: A process that change the location of the operand.
Elevating is a subtype of moving: A process that changes the location of the operand from a lower to a higher place or position.
Lowering is a subtype of moving: A process that changes the location of the operand from a higher to a lower place or position.
Moving fluid is a subtype of moving: A process that changes the location of the liquid.
Keeping position is a subtype of moving: A process that maintains in the fixed position.
Malfunctioning process is a subtype of function-related process: A process that cannot perform a function appropriately or cannot realize it at all.
Hyperfunctioning is a subtype of malfunctioning process: A process that performs an excessive function.
Hypofunctioning is a subtype of malfunctioning process: A process that performs a decreased or insufficient functioning.
Arresting function is a subtype of malfunctioning process: A process that arrests the progress of function execution.
Dysfunctioning is a subtype of malfunctioning process: A process that performs an abnormal and incomplete functioning.
Loss of function (process) is a subtype of malfunctioning process: A process that results in no longer having a function or the process that gradually loses it.
Negative regulation of phospholipase C mediated phosphatidylinositol is a subtype of negative regulation of phospholipase C mediated phospholipid degradation: A process that stops, prevents, or reduces the frequency, rate or extent of phospholipase C mediated phosphatidylinositol degradation.
negative regulation of phospholipase C mediated phosphatidylinositol degradation
Sifting is a subtype of changing between operands: A process to move an operand from one medium to another medium.
Changing medium from medium A to medium B.
Transmitting is a subtype of sifting: A process to send out an operand from a medium A to a medium B.
Hyperfunction of drug metabolism is a subtype of hyperfunctioning of metabolism: A process that performs an excessive drug metabolism. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
hyperfunction of drug metabolism [Ground glass appearance]
Caspase signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the caspase.
Caspase signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the caspase. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
caspase signaling (primitive) [ER stress]
Caspase signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the caspase. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
caspase signaling (primitive) [Cell death]
Death Domain sgnaling (primitive) is a subtype of signaling [biological]: A process in which a signal is transmitted from the cell membrane receptor starting with a ligand. The death domain at the cytoplsmic tail of the receptor binds the other death domain of the docking protein to form a death-inducing signaling complex (DISC).
This signal triggers the assembly of intracellular proteins to form a death including signaling complex (DISC), which includes a specific intiator procaspase (procaspase-8, 10). These initiator procasapases cleave and converts effector procaspases (i.e., caspase-3, 6, 7) to activate. Then, these effector caspases cleave target proteins, which leads to execute apoptosis.
extrinsic (Death Domain) signaling (primitive)
In hepatocytes, extrinsic pathway apoptosis induction requires caspase-9 mediated cleavage of Bid, a BCL-2 family protein and subsequent mitochondrial outer menbrane permeablization for executioner apoptosis activation. DRUG INDUCED LIVER DISEASE CHAPTER 5, 3rd Ed. Editors: Neil Kaplowitz Laurie DeLev
Death Domain signaling (primitive) is a subtype of signaling [biological]: A process in which a signal is transmitted from the cell membrane receptor starting with a ligand. The death domain at the cytoplsmic tail of the receptor binds the other death domain of the docking protein to form a death-inducing signaling complex (DISC). This entity is a specific course-dependent process. This process can constitute the course of Cell death.
extrinsic (Death domain) signaling (primitive) [Cell death]
NRF2 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal transmitted by the NRF2.
NRF2 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal transmitted by the NRF2. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
GRP78 - autophagy inducing factor (canonical)[ER stress - autophagy indution]
P53 signaling (primitive) isis a subtype of signaling [biological]: A process that in which a signal is transmitted by the p53. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
P53 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by p53. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
PERK signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the PERK. PERK generally plays a endoplasmic reticulum membrane stress sensor role. This entity is a specific course-dependent process. This process can constitute the course of PERK pathway.
PERK signaling (primitive) [PERK pathway]
Increasing demand for response to oxidative stress is a subtype of increasing the demand for response to oxidative stress: A process that changes the functional demand for the response to the oxidative stress to be higher. This entity is a specific course-dependent process. This process can constitute the course of Oxidative stress.
increasing demand for response to oxidative stress [Oxidative stress]
The directed movement of unfolded or misfolded proteins from the endoplasmic reticulum to the cytosol through the translocon. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
retrograde protein transport from ER to cytosol [ER stress]
The process that results in the movement of arachidonic acid from the cell membrane.
release of arachidonic acid from cell membrane
Removing (from A) is a subtype of taking: A process that takes an unnecessary operand from a medium.
Giving is a subtype of sifting: A process that provides an object to a medium.
ER to Golgi transport is a subtype of transport: A process of the directed movement of substances from the endoplasmic reticulum (ER) to the Golgi.
Oxidation-antioxidtion inbalance is a subtype of imbalance: A process that lacks a balance between oxidation and anti-oxidation that inhibits oxidation. This entity is a specific course-dependent process. This process can constitute the course of Oxidative stress.
oxidation-antioxidtion inbalance [Oxidative stress]
Detaching is a subtype of separating: A process that disaggregates the whole object into constituent components.
Dissociation of PERK:BIP heterodimer is a subtype of detaching: A process that disaggregates PERK-BIP heterodimers into BIP and PERK. This process is dependent on the translation attenuation and can constitute the course of ER stress.
PERK (EIF2AK3) is a single-pass transmembrane protein located in the Endoplasmic Reticulum (ER) membrane. PERK has an N-terminal luminal domain and a C-terminal cytosolic domain. It is maintained in an inactive state by association of its luminal domain with BiP, a chaperone in the ER. Because BiP also binds unfolded proteins, BiP dissociates from PERK when unfolded proteins exceed chaperone activity in the ER.
Dissociation of PERK:BIP Heterodimer [ER stress translation attenuation]
Changing position is a subtype of changing between operands: A process that that changes the relative position between objects.
Changing distance is a subtype of changing position: A process that changes the relative position between objects.
Increasing distance is a subtype of changing distance: A process that keeps object A away from object B.
Increasing free radical is a subtype of increasing quantity: A process that changes the amount of free radicals to be larger. This entity is a specific course-dependent process. This process can constitute the course of Oxidative stress.
increasing free radical [Oxidative stress]
Assembling is a subtype of changing composition: A process that combines multiple components as one configuration.
Joining is a subtype of combining: A process that makes bonds between the components.
Lysosome homeostasis is a subtype of homeostatic process: A process that that preserves a lysosome in a stable functional or structural state.
All of the lysosomal enzymes are acid hydrolases, which are active at the acidic pH (about 5) that is maintained within lysosomes but not at the neutral pH (about 7.2) characteristic of the rest of the cytoplasm (Figure 9.35). The requirement of these lysosomal hydrolases for acidic pH provides double protection against uncontrolled digestion of the contents of the cytosol; even if the lysosomal membrane were to break down, the released acid hydrolases would be inactive at the neutral pH of the cytosol.
Signaling is a subtype of transmitting: A process that transmits signals from medium A to medium B.
Ground glass appearance dependent molecule is a subtype of toxic course dependent chemical entity. This molecule can participate in the course of ground glass appearance as a gene product. Gene profile:caonical that described in textbooks or articles.
ground glass appearance dependent molecule (canonical)
Hyperfunction of increasing number is a subtype of hyperfunction of increasing: A process that performs an excessive nu,ber of the object.
Keeping quality is a subtype of changing quality: A process that keeps the quality of the object constant.
Changing pressure is a subtype of changing quality: A process that changes the pressure of the object .
Changing temperature is a subtype of changing quality: A process that changes the temperature of the object.
Insulin signaling (primitive) is a subtype of signaing (primitive), in which a signal mediated by insulin.
Hyperfunction of lipid transport to peroxisome is a subtype of hyperfunction of transport: A process that performs an excesssive lipid transport to peroxisome.
hyperfunction of long-chain fatty acid import into peroxisome
Hyperfunction of long-chain fatty acid import into peroxisome is a subtype of hyperfunction of transport: A process that performs an excesssive long-chain fatty acid import into peroxisome. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
hyperfunction of long-chain fatty acid import into peroxisome [Eosinophilic granular degeneration]
Hyperfunction of lipid transport to mitochondria is a subtype of hyperfunction of transport: A process that performs an excesssive lipid transport to mitochondria.
hyperfunction of lipid transport to mitochondria
A mebrane potential which is relatively low.
Insufficient functioning is a subtype of malfunctioning process: A process that lacks performing the function required.
Glutathione depletion is a subtype of depleting: A process that lessens markedly in the amount of glutathione.
Increasing autophagy is a subtype of increasing number of actions: A process that becomes larger in the number of autophagy.
ATP depletion is a subtype of depleting: A process that lessens markedly in the amount of adenosine triphosphate (ATP) .
ATP depletion is a subtype of depleting: A process that lessens markedly in the amount of adenosine triphosphate (ATP) . This entity is a specific course-dependent process. This process can constitute the course of Cell death.
Autophagy inducer is a role played by any compound that promotes the process of autophagy (the self-digestion of one or more components of a cell through the action of enzymes originating within the same cell).
Accumulation of fluids is a subtype of accumulation of substances in a biological object: A process that keeps fluid in an organism, tissue, organelle, or cell.
A laboratory test or analysis of the biological properties or activities of a substance performed by testing its effect on an organism.
Ligand molecule is a subtype of signaling dependent molecule. This entity is dependent on a signal transduction system and can participate in signaling process.
ligand molecule [signal transduction system]
A tube that is part of a excretory system.
Glycogen accumulation is a subtype of accumulation of substances in a biological object: A process that keeps glycogen in a biological object.
In the imbalance model, the basic units are as follows: 1) a functioning process (supply) for biological defense and maintaining homeostasis; 2) a functional demand process (demand) as toxic activity; 3) balance/imbalance between toxic activity and defense processes; and 4) outcome from organelles, cells, or tissues to the organ exhibiting toxicity manifestations. This entity is a compound state that inculdes step 1 to 4. The defense performance level is lower (L) than the medium (M) in the normal condition . Threfore even if the functional demand level is Medium level (M) in the daily life, which leads to the imbalance and leads to toxicity manifestation.
Hypofunction of ion transport is a subtype of hypofunction of transport: A process that performs a decreased or insufficient ion transport. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
hypofunction of ion transport [Phospholipidosis]
ICAD may influence a wide variety of cell functions, including: phosphorylation pathways, ion transport, and other metabolic pathways. In rat lung, amiodarone inhibits Mg2+-ATPase and Na+,K+-ATPase in areas where phospholipid is located . In this location and probably in others, CADs may affect ion transport and oxidative phosphorylation. These effects may be due to the increasing intracytoplasmic Ca2+.
Hypofunction of ion transport is a subtype of hypofunction of transport: A process that performs a decreased or insufficient ion transport.
Hypofunction of phospholipid degradation by PLA1 is a subtype of hypofunction of phospholipid deradation by phospholipase: A process that performs a decreased or insufficient phospholipid degradation by PLA1.
hypofunction of phospholipid degradation by PLA1
Hypofunction of phospholipid deradation by phospholipase A2 is a subtype of hypofunction of phospholipid degradation: A process that performs a decreased or insufficient phospholipid deradation by phospholipase A2. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
hypofunction of phospholipid degradation by phospholipase A2 [Phospholipidosis]
Hypofunction of phospholipid deradation by phospholipase C is a subtype of hypofunction of phospholipid degradation: A process that performs a decreased or insufficient phospholipid deradation by phospholipase C. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
hypofunction of phospholipid degradation by phospholipase C [Phospholipidosis]
Rat liver lysosomal phospholipase A hydrolyzes both acidic and neutral phospholipids. Numerous cationic amphiphilic drugs including imipramine, propranolol, 4,4'-bis(diethylaminoethoxy)-alpha, beta- diethyldiphenylethane and chloropromazine inhibit phospholipase A. Lysosomal storage of both acidic and neutral phospholipids appears to be caused by inhibition of lysosomal phospholipase action in view of the probable high intralysosomal levels of these agents.
Chloroquine also contains two basic amines on the hydrophilic side chain and induces clear cytoplasmic vacuoles and lysosomal lamellar bodies
The totality of all processes through which glutathione depletion is realized.
Mechanisms of liver injury. III. Role of glutathione redox status in liver injury.
Modulation of oxidative stress as an anticancer strategy.
Glutathione defense mechanism in liver injury: insights from animal models.
Hyperfunction of alcohol metabolism is a subtype of hyperfunctioning: A process that performs an excessive alcohol metabolism. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
hyperfunction of alcohol metabolism [Fibrosis]
Malfunctioning of regulation of gene expression is a subtype of malfunctioning of controlling: A process that cannot perform a regulation of gene expression appropriately or cannot realize it at all.
malfunctioning of regulation of gene expression
Dissociation of Bip complex is a subtype of detaching: A process that disaggregates a Bip complex into Bip and other molecule(s). This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Perturbation of protein folding promotes reversible dissociation of BiP from the lumenal domains of PERK and IRE1.
The ER luminal domains of the UPR sensors (PERK, IRE1, and ATF6) and unfolded proteins compete for binding sites on GRP78. When the UPR sensors are bound to GRP78, they are kept in an inactive state. Accumulation of unfolded proteins overwhelms the protein folding chaperones and sequesters them away from the UPR sensors unmasking oligomerization sequences in IRE1 and PERK or Golgi localization sequences in ATF6.
A role played by the entity which transfers directed movement of bile acid and bile salts out of a hepatocyte and into the bile canaliculus. Bile canaliculi are the thin tubes formed by hepatocyte membranes.
Bile acids are any of a group of steroid carboxylic acids occurring in bile, where they are present as the sodium salts of their amides with glycine or taurine.
canalicular bile acid transmembrane transporter
Activation of thioredoxin pathway is a subtype of activating: A process that changes the activity of the thioredoxin pathway to be higher.
Decreasing amount of abnormal protein is a subtype of decreasing quantity: A process that changes the quantity of the abnormal protein to be lower.
Any member of a group of steroid carboxylic acids occuring in bile, where they are present as the sodium salts of their amides with glycine or taurine.
In the small intestine, bile salts are essential for lipid digestion and the absorption of fat and fat soluble vitamin
bile salts have detergent properties and can easily become cytotoxic.
Apoptosis triggered by inadequate or inappropriate adherence to substrate e.g. after disruption of the interactions between normal epithelial cells and the extracellular matrix. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
After an initiall adaptation phase (UPR), continued ER sress may lead to an irresible phase involving commitenent to apoptosis. Perk leads to upregulation of the transcription factor CHOP and mitochondria-mediated cell death.
A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died. This entity is a specific course-dependent process. This process can constitute the course of Oxidative stress.
The chemical reactions and pathways resulting in the breakdown of a protein by the destruction of the native, active configuration, with or without the hydrolysis of peptide bonds. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Increasing demand for response to oxidative stress is a subtype of increasing the demand for response to stress: A process that changes the functional demand for the response to the oxidative stress to be higher. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
increasing demand for response to oxidative stress [ER stress]
This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. The protein is expressed in a broad range of cell types, acts as a pleiotropic cytokine and is involved in the stress response program of cells after cellular injury. Increased protein levels are associated with disease states such as tissue hypoxia, inflammation, acute injury and oxidative stress. [provided by RefSeq, Aug 2016]
Growth differentiation factor 15 deficiency protects against atherosclerosis by attenuating CCR2-mediated macrophage chemotaxis. J. Exp. Med. 208: 217-225, 2011.
Adaptive induction of growth differentiation factor 15 attenuates endothelial cell apoptosis in response to high glucose stimulus.
Growth differentiation factor-15 encodes a novel microRNA 3189 that functions as a potent regulator of cell death.
Catalysis role of an oxidation-reduction (redox) reaction, a reversible chemical reaction in which the oxidation state of an atom or atoms within a molecule is altered. One substrate acts as a hydrogen or electron donor and becomes oxidized, while the other acts as hydrogen or electron acceptor and becomes reduced.
The difference in distribution of cell death depends on the location of the toxic expression.
Zone 3 hepatocytes are rich in P450, which produce drug metabolites to cause cell death.
classification of cell death by distribution
Centrilobular necrosis is a subtype of classification of cell death by distribution: A hepatocyte necrosis localized around centrilobular zone.
Periportal necrosis is a subtype of classification of cell death by distribution: A hepatocyte necrosis localized around the portal vein.
Zonal necrosis is a subtype of classification of cell death by distribution: A hepatocyte necrosis localized around hepatic the lobule such as centrilobular (acinar zone 3) necrosis, midzonal (midlobular) necrosis, and periportal (perilobular) necrosis.
Expanding inflammation is a subtype of increasing quantity: A process that changes the magnitude of the inflammation the object to be larger.
Expanding inflammation is a subtype of increasing quantity: A process that changes the magnitude of the inflammation the object to be larger. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
Leaking content from cell is a subtype of leaking: A process that leaks contents from the cell.
Leaking content from cell is a subtype of leaking: A process that leaks contents from the cell. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
NAPQI production is a subtype of generating a substance : A process that synthesizes NAPQI (N-acetyl-p-benzoquinone imine) as output.
The human acid ceramidase gene (ASAH): structure, chromosomal location, mutation analysis, and expression.
Insertional mutagenesis of the mouse acid ceramidase gene leads to early embryonic lethality in homozygotes and progressive lipid storage disease in heterozygotes.
Acid ceramidase and human disease. Acid ceramidase (N-acylsphingosine deacylase, EC 3.5.1.23; AC) is the lipid hydrolase responsible for the degradation of ceramide into sphingosine and free fatty acids within lysosomes. Recent studies have also shown that AC activity is aberrantly expressed in several human cancers. Overexpression of AC may prevent insulin resistant (Type II) diabetes induced by free fatty acids.
ASAH1 is an estrogen-dependent member of the sphingolipid metabolism, which might provide further prognostic information in ER-positive breast cancers.
Acid ceramidase as a therapeutic target in metastatic prostate cancer.
A Conserved Circular Network of Coregulated Lipids Modulates Innate Immune Responses.
Malfunctioning of controlling is a subtype of malfunctioning process: A process that cannot perform a controlling function appropriately or cannot realize it at all.
Cell repair is a subtype of repairing: A process that restores the cell after damage.
Cell repair is a subtype of repairing: A process that restores the cell after damage. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
Repairing is a subtype of changing an operand: A process that restores the object after damage.
JNK signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the JNK (a stress-activated protein kinase (SAPK) ). This entity is a specific course-dependent process. This process can constitute the course of Oxidative stress.
JNK signaling (primitive) [Oxidative stress]
Extracellular matrix excess deposition is a subtype of accumulation of substances in a biological object: A process that puts extracellular matrix down in an organism, tissue, organelle, or cell.
A type of cell death that is morphologically characterized by an increasingly translucent cytoplasm, swelling of organelles, minor ultrastructural modifications of the nucleus (specifically, dilatation of the nuclear membrane and condensation of chromatin into small, irregular, circumscribed patches) and increased cell volume (oncosis), culminating in the disruption of the plasma membrane and subsequent loss of intracellular contents. Necrotic cells do not fragment into discrete corpses as their apoptotic counterparts do. Moreover, their nuclei remain intact and can aggregate and accumulate in necrotic tissues. This entity is a specific course-dependent process. This process can constitute the course of Phosphoipidosis(severe).
Massive Lysosomal membrane permeabilization (LMP) often results in cell death without caspase activation; this cell death may adopt a subapoptotic or necrotic appearance. The regulation of LMP is perturbed in cancer cells, suggesting that specific strategies for LMP induction might lead to novel therapeutic avenues.
Inflammatory cell infiltration is a subtype of moving A to the inside of B: A process that moves the outside inflammatory cell to the inside in response to an inflammatory reaction.
Inflammatory cell infiltration is a subtype of moving A to the inside of B: A process that that moves the outside inflammatory cell to the inside in response to an inflammatory reaction. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
inflammatory cell infiltration [Cell death]
Abnormality of membrane is a subtype of changing abnormal cellular structure: A process that changes the membrane stucture abnormally. This entity is a specific course-dependent process. This process can constitute the course of Oxidative stress.
abnormality of membrane [Oxidative stress]
Lipoperoxidation is a subtype of lipid oxidation: The degradation of lipids caused by an oxidative attack from free radicals. This entity is a specific course-dependent process. This process can constitute the course of Oxidative stress.
Changing area is a subtype of changing quality: A process that changes the area of the object.
Increasing cell volume is a changing process to change the volume of the cell to increase. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
Toxicant induced cholestasis is associated with cell swelling, cell death, and inflammation
Any process that increases the frequency, rate or extent of the passage or uptake of molecules by the mitochondrial membrane. This entity is a specific course-dependent process. This process can constitute the course of Oxidative stress.
positive regulation of mitochondrial membrane permeability [Oxidative stress]
The sodium dependent uptake of bile salts is mediated by the NTCP (sodium/bile acid cotransporter; SLC10A1), which is expressed in a polar manner at the basolateral plasma membrane of hepatocytes. NTCP has a preference for conjugated bile salts.
Na/taurocholate cotransporting polypeptide [Cholestasis]
Negative regulation of cell cycle is a subtype of negative regulation process: Any process that stops, prevents or reduces the rate or extent of progression through the cell cycle.
Phosphorylation of eIF2-alpha by PERK is a subtype of eIF2a phosphorylation: A process that The process of introducing a phosphate group into eIF2a by PERK.
Changing length is a subtype of changing quality: A process that changes the length of the object.
Leaking content from cell is a subtype of leaking: A process that leaks contents from the cell. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
leaking content from cell [Phospholipidosis]
Negative regulation of phospholipase C mediated phospholipid degradation is a subtype of negative regulation of phospholipid degradation: A process that stops, prevents, or reduces the frequency, rate or extent of phospholipase C mediated phospholipid degradation.
negative regulation of phospholipase C mediated phospholipid degradation
Sorting transport signal of NPC1 / NPC2 is a subtype of extractng: A process that obtains a necessary NPC1/NPC2 transport signal.
Any process that increases the rate, frequency or extent of macrophage derived foam cell differentiation. Macrophage derived foam cell differentiation is the process in which a macrophage acquires the specialized features of a foam cell. The degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
positive regulation of macrophage derived foam cell differentiation [Phospholipidosis (severe)]
A role played by the entity that inhibits the catalysis of the hydrolysis of a phospholipid.
Ground glass appearance dependent chemical compound is a subtype of toxic course dependent chemical entity. This entity (drug) can participate in the course of ground glass appearance.
ground glass appearance dependent chemical compound
HYOU1 - chaperone -vitro (human)[ER stress]
A role played by the entity that inhibits the catalysis of the reaction: a phospholipid + H2O = 1,2-diacylglycerol + a phosphatidate.
A molecular messenger in which the molecule is specifically involved in transmitting information between cells. Such molecules are released from the cell sending the signal, cross over the gap between cells by diffusion, and interact with specific receptors in another cell, triggering a response in that cell by activating a series of enzyme controlled reactions which lead to changes inside the cell.
Catalysis role of the reaction: donor + hydrogen peroxide = oxidized donor + 2 H2O.
Calcium ion homeostasis imbalance is a subtype of chemical homeostasis imbalance: A process that becomes lacking a calcium ion homeostastasis balance. This entity is a specific course-dependent process. This process can constitute the course of Oxidative stress.
calcium ion homeostasis imbalance [Oxidative stress]
Imbalance is a subtype of changing balance: A process that becomes lacking a correct balance between operands.
Homeostasis imbalance is a subtype of imbalance: A process that becomes lacking a homeostastasis balance. Imbalance of homeostasis in the body is a lacking balance between performing amounts of defense (supply) and required amounts of protection (demand) in the maintenance of an internal state.
Endoplasmic reticulum stress response imbalance is a subtype of stress response imbalance: A process that lacks a balance between the stimulation (stress) acting on the endoplasmic reticulum and the biological defence response. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
endoplasmic reticulum stress response imbalance [ER stress]
Stress response imbalance is a subtype of imbalance: A process that lacks a balance between the stimulation (stress) and the response.
Endoplasmic reticulum stress response imbalance is a subtype of stress response imbalance: A process that lacks a balance between the stimulation (stress) acting on the endoplasmic reticulum and the biological defence response.
endoplasmic reticulum stress response imbalance
Protein quality control imbalance is a subtype of imbalance: A process that lacks a balance between abnormal protein (misfolded or attenuated proteins) production and breakdown.
Increasing demand for response to ER stress is a subtype of increasing the demand for response to stress: A process that changes the functional demand for the response to the endoplasmic reticulum (ER) stress to be higher. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
increasing demand for response to ER stress [Cell death]
Increasing demand for response to oxidative stress is a subtype of increasing the demand for response to stress: A process that changes the functional demand for the response to the oxidative stress to be higher. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
increasing demand for response to oxidative stress [cell death]
Metabolic intermediate accumulation is a subtype of accumulation of substances in a biological object: A process that keeps intermediate(s) of metabolism in an organism, tissue, organelle, or cell.
Decreasing pH is a subtype of changing pH: A process that changes the pH to be lower.
Decreasing cellular pH is a subtype of decreasing pH: A process that changes the celular pH to be lower.
Decreasing cellular pH is a subtype of decreasing pH: A process that changes the celular pH to be lower. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
Ischemia is a changing process to lack enough to blood supply.
This gene encodes a glycosylated, secreted protein containing a C-terminal fibrinogen domain. The encoded protein is induced by peroxisome proliferation activators and functions as a serum hormone that regulates glucose homeostasis, lipid metabolism, and insulin sensitivity. This protein can also act as an apoptosis survival factor for vascular endothelial cells and can prevent metastasis by inhibiting vascular growth and tumor cell invasion. The C-terminal domain may be proteolytically-cleaved from the full-length secreted protein. Decreased expression of this gene has been associated with type 2 diabetes. Alternative splicing results in multiple transcript variants. This gene was previously referred to as ANGPTL2 but has been renamed ANGPTL4. [provided by RefSeq, Sep 2013]
Hepatic expression, synthesis and secretion of a novel fibrinogen/angiopoietin-related protein that prevents endothelial-cell apoptosis.
ANGPTL4 deficiency in macrophages results in increase in foam cell formation, inflammation and apoptosis
Ischemia is a changing process to lack enough to blood supply. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
ATF6 (ATF6-alpha) activates chaperone genes is a subtype of molecular activation: A process that changes the activity of the molecule with chaperone role to be higher by ATF6.
ATF6 (ATF6-alpha) activates chaperone genes
Regulation of Cxcl2 expression by TNF-alpha is a subtype of regulation of gene expression by TNF-alpha: A process that Any process that modulates the frequency, rate or extent of Cxcl2 expression by TNFalpha.
TNFalpha->JNK->AP-1->CXCL1 mRNA expression TNFalpha->p38MAPK->PI3K->AKT->CXCL1 release from the cell membrane
CXCL1 is one of the members of chemokines, which are small heparin-binding proteins that generally direct the movement of circulating leukocytes to sites of inflammation or injury. TNF-α stimulates CXCL1 release from human ECs through JNK-mediated CXCL1 mRNA expression and p38 MAPK- and PI-3K-mediated CXCL1 secretory processes.
regulation of Cxcl2 expression by TNF-alpha
Regulation of gene expression by TNF-alpha is a subtype of molecular activation: Any process that modulates the frequency, rate or extent of gene expression by TNFalpha.
regulation of gene expression by TNF-alpha
PERK activation is a subtype of Molecular activation: A process that changes the activity of PERK to be higher. This entity is a specific course-dependent process. This process can constitute the course of PERK pathway.
Change in H+ ion concentrations is a subtype of changing concentration: A process that changes the hydrogen ion (H+) concentration in the blood.
Changing weight is a subtype of changing quality: A process that changes the weight of the object.
Bile reflux is a subtype of back-flow: A process that changes the bile flow to the opposite direction.
Members of the class of phenols that contain 2 or more benzene rings each of which is substituted by at least one hydroxy group
Oxidative stress dependent molecule is a subtype of toxic course dependent chemical entity. This molecule can participate in the course of oxidative stress as a gene product. Gene profile:Human/in vitro/Hepatocyte/
oxidative stress dependent molecule (human in vivo)
Types of hepatobiliary injury: Fatty liver: Amiodarone, CCl4, ethanol, fialuridine, tamoxifen, valproic acid in Table 13-2. Casarett & Doull's Toxicology: The Basic Science of Poisons, Eighth Edition
Oxidative stress dependent molecule is a subtype of toxic course dependent chemical entity. This molecule can participate in the course of oxidative stress as a gene product. Gene profile:caonical that described in textbooks or articles.
oxidative stress dependent molecule (caonical)
Oxidative stress dependent molecule is a subtype of toxic course dependent chemical entity. This molecule can participate in the course of oxidative stress as a gene product. Gene profile:Rat/Liver
oxidative stress dependent molecule (rat)
Hyperfunction of cell survival is a subtype of hyperfunctioning: A process that performs an excesssive cell survival. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (excessive defense).
hyperfunction of cell survival [Ground glass appearance]
A role played by the entity to perform peroxiidation of the target object.
Plc gamma1 (rat)[Ground glass appearance]
Meta-functioning process is a type of function-related process that executes a function for another function.
For example, the 'to vaporize' function of the boiler is to perform a meta-function to enable for the 'to rotate' function of the turbine. The meta-functions are result of teleological interpretation of causal relations among base-functions of different components (i.e., inter-components relations).
Kitamura Y. Advanced Engineering Informatics (former Artificial Intelligence in Engineering), Vol. 16, No. 2, pp. 145-163, 2002.
Storing is a subtype of receiving: A process that keeps target object(s).
Depleting is a subtype of decreasing quantity: A process that that lessens markedly in quantity of the object to nearly zero.
Pathway system is a subtype of object aggregates. This entity has sub-parts and has a goal of transmitting as a systemic context.
CREB3L3 signaling is a subtype of signaling [biological]: A process that in which a signal transmitted by CREB3L3.
Hypofunction of ATP biosynthesis is a subtype of hypofunction of biosynthesis: A process that performs a decreased or insufficient ATP biosynthesis. This entity is a specific course-dependent process. This process can constitute the course of Oxidative stress.
hypofunction of ATP biosynthesis [Oxidative stress]
Catalysis role of the transfer of a group, e.g. a methyl group, glycosyl group, acyl group, phosphorus-containing, or other groups, from one compound (generally regarded as the donor) to another compound (generally regarded as the acceptor). Transferase is the systematic name for any enzyme of EC class 2.
Maintaining mitochondrial membrane permeability is a subtype of maintaining membrane permeability is a changing process to keep the permeability of the membrane: A process that keeps the permeability of the mitochondrial membrane.
maintaining mitochondrial membrane permeability
Process sequence is a subtype of occurrents that is a series of process.
Signaling pathway is a subtype of pathway: Sequence of linked reactions in which a signal is transmitted to other(s).
1. signal detection (acceptance), 2. signal transduction, 3. gene regulation (genetic information conversion process), 4. celllular process execution This entity covers from 1 to 2.
Metabolic pathway is a subtype of pathway: Sequence of enzyme reactions to change metabolism, including anabolism and catabolism.
A series of molecular signals mediated by death-domain superfamily.
The process in which the anatomical structures of the nodule are generated and organized.
GO:0009877 nodule morphogenesis is part of some nodulation. However, nodulation is defined as the formation of nitrogen-fixing root nodules on plant roots. Therefore, TXPO does not reuse GO terms and defines originally.
A data item is an information content entity that is intended to be a truthful statement about something (modulo, e.g., measurement precision or other systematic errors) and is constructed/acquired by a method which reliably tends to produce (approximately) truthful statements.
Increasing volume of liver is a subtype of increasing volume: A process that changes the volume of the liver to be higher.
A peptide containing ten or more amino acid residues.
Increasing ROS/RNS is a process of changing amount to increase the magnitude of the ROS or RNS.
Removing damaged object is a subtype of removing: A process that takes a damaged object from an organism, tissue, organelle, or cell.
Removing damaged organelle is a subtype of removing damaged object: A process that takes a damaged organelle from a cell.
Negative regulation of phospholipase C mediated phosphatidylcholine degradation is a subtype of negative regulation of phosphatidylcholine catabolic process: A process that stops, prevents, or reduces the frequency, rate or extent of phospholipase C mediated phosphatidylcholine degradation.
negative regulation of phospholipase C mediated phosphatidylcholine degradation
A signaling role played by the entity such as protein, polypeptide, or glycoprotein that acts on neighboring cells to alter their behavior.
Extracellular signal protein or peptide that acts as a local mediator in cell-cell communication.
A role of regulating receiving process of receptors such that the proportion of receptors in the active form is changed.
A role played by the entity that Interacts selectively and non-covalently with one or more specific sites on a receptor molecule, a macromolecule that undergoes combination with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function.
Binding to a specific receptor protein and activating intracellular signaling cascades that alter the behavior of the cell.
A role played by the entity to increase number of operand(s)
A role played by the entity to replicate DNA.
Removing damaged cell is a subtype of removing damaged object: A process that takes a damaged cell from an organism or tissue.
Negative regulation of phopholipase C mediated phosphatidyliserine degradation is a subtype of negative regulation of phosphatidylserine degradation: A process that stops, prevents, or reduces the frequency, rate or extent of phopholipase C mediated phosphatidyliserine degradation.
negative regulation of phopholipase C mediated phosphatidyliserine degradation
Negative regulation of phopholipase C mediated phosphatidylinositol degradation is a subtype of negative regulation of phosphatidylinositol degradation: A process that stops, prevents, or reduces the frequency, rate or extent of phopholipase C mediated phosphatidylinositol degradation.
negative regulation of phopholipase C mediated phosphatidylinositol degradation
Negative regulation of phospholipase C mediated phosphatidylinositol is a subtype of negative regulation of phospholipase C mediated phospholipid degradation: A process that stops, prevents, or reduces the frequency, rate or extent of phospholipase C mediated phosphatidylinositol degradation. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
negative regulation of phospholipase C mediated phosphatidylinositol degradation [Phospholipidosis]
Removing xenobiotics is a subtype of taking process: A process that removes xenobiotics from an organ, tissue, cell, organelle, or makes a clearance of it from the body.
Increasinging length of time is a subtype of changing length of time: A process that changes the length of time to be longer.
Increasing functional demand is a subtype of increasing quantity: A process changes the functional demand to be higher.
Signal transduction system is a subtype of pathway system. This entity has sub-parts and has a goal of transmitting signals as a systemic context.
Hyperfunction of Kupffer cell differentiation is a subtype of hyperfunction of cell differentiation: A process that performs an excesssive kupffer cell differentiation. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
hyperfunction of Kupffer cell differentiation [Phospholipidosis]
Negative regulation of phopholipase C mediated phosphatidyliserine degradation is a subtype of negative regulation of phosphatidylserine degradation: A process that stops, prevents, or reduces the frequency, rate or extent of phopholipase C mediated phosphatidyliserine degradation. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
negative regulation of phopholipase C mediated phosphatidyliserine degradation [Phospholipidosis]
Inflammatory cytokine gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature inflammatory cytokine gene product or products (proteins or RNA). This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
inflammatory cytokine gene expression [Cholestasis]
IRE1->JNK->AP-1->inflammatory response IRE1->XBP1s->IL6, IL8, MCP1 IRE1->IKK->NfkB ATF6->NfkB Perk->reducedIkB->NfkB
Increasing AST concentration in blood is a subtype of increasing concentration: A process that changes the aspartate amino transferase (AST) concentration to be higher.
Decreasing lipid is a subtype of decreasing quantity: A process that changes the quantity of the lipid to be lower.
Negative regulation of phospholipase C mediated phosphatidylcholine degradation is a subtype of negative regulation of phosphatidylcholine catabolic process: A process that stops, prevents, or reduces the frequency, rate or extent of phospholipase C mediated phosphatidylcholine degradation. This process is dependent on the phosphatidylcholine disorder and can constitute the course of Phospholipidosis.
negative regulation of phospholipase C mediated phosphatidylcholine degradation [Phospholipidosis - phosphatidylcholine disorder]
Negative regulation of phospholipase C mediated phospholipid degradation is a subtype of negative regulation of phospholipid degradation: A process that stops, prevents, or reduces the frequency, rate or extent of phospholipase C mediated phospholipid degradation. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
negative regulation of phospholipase C mediated phospholipid degradation [Phospholipidosis]
Eosinogranular degeneration dependent molecule is a subtype of toxic course dependent chemical entity. This gene can participate in the course of eosinogranular degeneration as a gene product. Gene profile:Mouse/Liver/
eosinogranular degeneration dependent molecule (mice)
ACOT12 metastasis inhibitor (human)[Eosinophilic granular degeneration]
ACOT12 suppresses HCC metastasis both in vitro and in vivo. Further mechanistic studies reveal that ACOT12 regulates the cellular acetyl-CoA levels and histone acetylation in HCC cells and that down-regulation of ACOT12 promotes HCC metastasis by epigenetically inducing TWIST2 expression and the promotion of epithelial-mesenchymal transition
Pathogen colonization is a subtype of making existence of xenobiotics. A process that makes the existence of the colony of a pathogen (after infection).
The pathways resulting in the formation of glutathione, the tripeptide glutamylcysteinylglycine, which acts as a coenzyme for some enzymes and as an antioxidant in the protection of sulfhydryl groups in enzymes and other proteins.
Aldo-keto reductase-7A protects liver cells and tissues from acetaminophen-induced oxidative stress and hepatotoxicity: In response to APAP or NAPQI exposure, Akr7a3 mRNA and protein were significantly up-regulated in vitro in human HepG2 and LO2 cells. Similarly, strong induction was observed for Akr7a5 in mouse AML12 hepatocytes exposed to APAP. In vivo in wild-type rats, significant up-regulation of hepatic AKR7A1 protein was observed after administration of APAP. On the other hand, depletion of Nrf2 reduced the expression of Akr7a3, suggesting that Nrf2, indeed, contributes significantly to the induction of Akr7a.
Hyperfunction of antioxidant gene expression is a subtype of hyperfunction of gene expression: A process that performs an excesssive antioxidant gene expression. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
hyperfunction of antioxidant gene expression [Glutathione depletion]
antixidant gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) involved in antioxidant process. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
antioxidant gene expression [Gutathione depletion]
A physical quality that inheres in a bearer by calculation under some condition.
hyperfunction of antioxidant gene expression
MMAA (predicted)(human)[Phospholipidosis]
Changing protein structure is a subtype of changing structure: A process that changes the stucture of the protein.
ECM2 (predicted)(human)[Glutathione depletion]
Cytoplasmic alternation [Liver PathologicalFindings] is a type of finding observed in the liver. Lesions are observed as changes in cytoplasm based on pathological morphology.
Changes in cytoplasm in the hepatocytes. Liver is responsible for drug metabolism; therefore these findings are most frequently observed results in drug safety studies. It shows various morphological images depending on the kind of chemical substance.
cytoplasmic change [Liver PathologicalFindings]
cytoplasmic alternation [Liver Pathological Findings]
ALDOB (predicted)(human)[Glutathione depletion]
The downregulation of ALDOB could indicate a poor prognosis for HCC patients, and therefore, ALDOB might be considered a prognostic biomarker for HCC, especially at the early stage.
The down-regulated expression of altered proteins (ALDOB, GAPDH, Pgk1, Eno3, and LDHBB) inhibited the glycolysis pathway, but inversely activated NADPH through pentose phosphate pathway (PPP). Simultaneously, NADPH stimulated ROS production, then activated the antioxidant system and NF-κB pathway by enhancing the expression of GPx1, GSTm, and HSP70, which synergically enhanced the antioxidant mechanism.
Identification of the Consistently Altered Metabolic Targets in Human Hepatocellular Carcinoma: ALDOB, ENO3, and PFKFB1 are down-regulated, as are some glucose transporters. Although it is unclear if HCC actually require the down-regulation of these genes for optimal glycolysis, their suppressed expression seem to be beneficial for cancer cells. For instance, previous study show that low ALDOB expression influence aggressiveness and predict patients survival outcome in HCC. In our analysis, low expression of ALDOB and also PFKFB1 predicted overall survival. We detected ALDOB at protein level and its expression varied with tumor size.
Caspase signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the caspase. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
caspase signaling (primitive) [Phospholipidosis (excessive defense) ]
Induction of apoptosis by cationic amphiphilic drugs amiodarone and imipramine.
Aldolase B inhibits metastasis through Ten-Eleven Translocation 1 and serves as a prognostic biomarker in hepatocellular carcinoma.
Any process that modulates the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product or products (proteins or RNA). This includes the production of an RNA transcript as well as any processing to produce a mature RNA product or an mRNA or circRNA (for protein-coding genes) and the translation of that mRNA or circRNA into protein. Protein maturation is included when required to form an active form of a product from an inactive precursor form. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
regulation of gene expression [Cell death]
A role played by the entity which responses to any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of oxidative stress, a state often resulting from exposure to high levels of reactive oxygen species, e.g. superoxide anions, hydrogen peroxide (H2O2), and hydroxyl radicals.
related process GO:0006979 response to oxidative stress
The cell cycle process by which a cell in G1 phase commits to S phase. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
cell cycle G1/S phase transition [Ground glass appearance]
Exposure to ethanol induces steatosis, which may enhance the subsequent inflammatory insults. Casarett & Doull's Toxicology: The Basic Science of Poisons, Eighth Edition
Decreasing concentration is a subtype of changing concentration: A process that changes the concentration of the object to be lower.
Starvation is a subtype of depleting: A process that lessens markedly in quantity of the nourishment.
PERK autophosphorylation is a subtype of protein autophosphorylation: The phosphorylation by PERK of one or more of its own amino acid residues (cis-autophosphorylation), or residues on PERK (trans-autophosphorylation). This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Any process that stops, prevents, or reduces the frequency, rate or extent of glycolysis. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
negative regulation of glycolytic process [Glutathione depletion]
Catalysis of the reaction: D-fructose-1-phosphate = dihydroxyacetone phosphate + D-glyceraldehyde.
The totality of all processes through which oxidative stress is realized.
Generation of free radicals or depletion of free radical scavengers and other antioxidant defences such as glutathione -> generation of reactive oxyen metabolites ->damaging effects on cell
Necrosis (course) is a subtype of cell death (course). The totality of all processes through which necrosis is realized.
Necrosis is a type of cell death that is morphologically characterized by an increasingly translucent cytoplasm, swelling of organelles, minor ultrastructural modifications of the nucleus (specifically, dilatation of the nuclear membrane and condensation of chromatin into small, irregular, circumscribed patches) and increased cell volume (oncosis), culminating in the disruption of the plasma membrane and subsequent loss of intracellular contents. necrotic cells do not fragment into discrete corpses as their apoptotic counterparts do. moreover, their nuclei remain intact and can aggregate and accumulate in necrotic tissues.
In the imbalance model, the basic units are as follows: 1) a functioning process (supply) for biological defense and maintaining homeostasis; 2) a functional demand process (demand) as toxic activity; 3) balance/imbalance between toxic activity and defense processes; and 4) outcome from organelles, cells, or tissues to the organ exhibiting toxicity manifestations. This entity is a compound state that includes step 1 to 4, and the defense performance level is very higher (VH) than usual which leads to imbalance and toxicity manifestations.
toxicological imbalance VH< (excess biodefense function)
In the imbalance model, the basic units are as follows: 1) a functioning process (supply) for biological defense and maintaining homeostasis; 2) a functional demand process (demand) as toxic activity; 3) balance/imbalance between toxic activity and defense processes; and 4) outcome from organelles, cells, or tissues to the organ exhibiting toxicity manifestations. This entity is a compound state that inculdes step 1 to 4. The defense performance level is Moderate (M) in the normal coindition; however, the functional demand level is High (H), which leads to the imbalance.
Scarring is a subtype of changing material: A process of keeping area replaced into fibrous tissue by injury.
Maintaining balance is a subtype of changing balance: A process that keeps the steady state between operands.
Maintaining stress response balance is a subtype of maintaining balance: A process that keeps a balance between the stimulation (stress) and the response.
Maintaining endoplasmic reticulum stress response balance is a subtype of maintaining stress response balance: A process that keeps a balance between the stimulation (stress) acting on the endoplasmic reticulum and the biological defence response.
maintaining endoplasmic reticulum stress response balance
Maintaining endoplasmic reticulum stress response balance is a subtype of maintaining stress response balance: A process that keeps a balance between the stimulation (stress) acting on the endoplasmic reticulum and the biological defence response. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
maintaining endoplasmic reticulum stress response balance [ER stress]
Increasing demand for response to ER stress (moderate) is a subtype of increasing the demand for response to ER stress: A process that changes the functional demand for the response to the edoplasmic reticulum (ER) stress to be moderately higher.
increasing demand for response to ER stress (moderate)
Increasing demand for response to ER stress (mild) is a subtype of increasing the demand for response to ER stress: A process that changes the functional demand for the response to the edoplasmic reticulum (ER) stress to be mildly higher.
increasing demand for response to ER stress (mild)
Increasing demand for response to ER stress is a subtype of increasing the demand for response to stress: A process that changes the functional demand for the response to the edoplasmic reticulum (ER) stress to be higher. This entity is a specific course-dependent process. This process can constitute the course of ER stress (mild).
increasing demand for response to ER stress [ER stress (mild) ]
Increasing demand for response to ER stress is a subtype of increasing the demand for response to stress: A process that changes the functional demand for the response to the edoplasmic reticulum (ER) stress to be higher. This entity is a specific course-dependent process. This process can constitute the course of ER stress (moderate).
increasing the demand for response to ER stress [ER stress] [ER stress (moderate) ]
reduced oxygenation of body tissues resulting in the decreased pressure of this component of body gases; commonly due to hypoxemia This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Lysosomal proliferation in hepatocyte is a subtype of increasing number of organelle: A process that becomes larger in the number of lysosome in hepatocyte(s).
The chemical reactions and pathways resulting in the formation of glycolipid, a class of 1,2-di-O-acylglycerols joined at oxygen 3 by a glycosidic linkage to a carbohydrate part (usually a mono-, di- or tri-saccharide). This entity is a specific course-dependent process. This process can constitute the course of ER stress.
glycolipid biosynthetic process [ER stress]
Lysosomal cholesterol storage is a subtype of cholesterol storage: A process that keeps cholesterol in the lysosome. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
lysosomal cholesterol storage [Phospholipidosis]
ER stress response gene expression via PERK is a subtype of gene expression: The process in which a gene sequence is converted into a mature ER stress response gene product or products (proteins or RNA) by PERK. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
ER stress response gene expression via PERK [ER stress]
A process that changes the activity of the eIF2a by PERK. This entity is a specific course-dependent process. This process can constitute the course of PERK - eIF2A pathway.
changing activity of eIF2a by PERK [PERK - eIF2A pathway]
EIF2a phosphorylation is a subtype of phosphorylation: The process of introducing a phosphate group into eIF2a. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Gene expression by ATF4 is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) by ATF4. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
ATF4 is a transcription factor and activates expression of IL-8, MCP1, IGFBP-1, CHOP, HERP1 and ATF3.
ATF4 is a bZIP transcription factor that controls the regulation of expression of pro-survival UPR-target genes (e.g., the chaperones glucose regulated protein [GRP]78 and GRP94) as well as genes involved in other functions such as redox homeostasis, amino acid metabolism, apoptosis, and autophagy.
Changing velocity is a subtype of changing quality: A process that chnges the velocity of the object.
Phosphorylation of eIF2-alpha by PERK is a subtype of eIF2a phosphorylation: A process that The process of introducing a phosphate group into eIF2a by PERK. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
The C-terminal domain of PERK (EIF2AK3) has kinase activity when PERK homodimerizes. PERK kinase specifically phosphorylates Ser52 of eIF2-alpha, causing an arrest in translation. The result is that translation of ER-targeted proteins is halted on ribosomes in the vicinity of activated PERK. The general arrest of translation results in the loss of short-lived proteins such as Cyclin D1, causing an arrest of the cell cycle in G1.
Phosphorylation of eIF2-alpha by PERK [ER stress]
Nature. 1999 Jan 21;397(6716):271-4. Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Erratum in Nature 1999 Mar 4;398(6722):90. Protein synthesis and the folding of the newly synthesized proteins into the correct three-dimensional structure are coupled in cellular compartments of the exocytosis pathway by a process that modulates the phosphorylation level of eukaryotic initiation factor-2alpha (eIF2alpha) in response to a stress signal from the endoplasmic reticulum (ER). Activation of this process leads to reduced rates of initiation of protein translation during ER stress. ER stress increases PERK's protein-kinase activity and PERK phosphorylates eIF2alpha on serine residue 51, inhibiting translation of messenger RNA into protein. These properties implicate PERK in a signalling pathway that attenuates protein translation in response to ER stress. Comment in Translational control perks up. [Nature. 1999]
PERK-eIF2a signaling (integrated pathway) is a subtype of PERK signaling (integrated pathway): Sequence of linked reactions, which has PERK-eIF2a signaling and gene regulation pathway.
PERK-eIF2a signaling (integrated pathway)
Expression of CHOP (DDIT3, GADD153) is a subtype of gene expression: The process in which a gene sequence is converted into a mature CHOP (DDIT3, GADD153) gene product or products (proteins or RNA).
Expression of CCL2 is a subtype of inflammatory cytokine gene expression: A process that convert a CCL2 (C-C Motif Chemokine Ligand 2) gene's sequenes into a mature gene prduct(s), i.e., (m)RNA, or protein.
The CCL2 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
IGFBP1 activation is a subtype of molecular activation: A process that changes the activity of the IGFBP1 (Insulin Like Growth Factor Binding Protein 1) to be higher.
ATF4 gene expression by eIF2a is a subtype of gene expression: The process in which a gene sequence is converted into a mature ATF4 gene product or products (proteins or RNA) by eIF2a.
Phosphorylation of eIF2-alpha causes increased translation of ATF4 mRNA. In mouse the mRNA of ATF4 contains 2 upstream ORFs (uORFs) (Vattem and Wek 2004). The second uORF overlaps the ORF encoding ATF4 and thus prevents translation of ATF4. When eIF2-alpha is phosphorylated, translation of the uORFs is suppressed and translation of the ORF encoding ATF4 is increased.
ATF4 gene expression by eIF2a is a subtype of gene expression: The process in which a gene sequence is converted into a mature ATF4 gene product or products (proteins or RNA) by eIF2a. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
ATF4 gene expression by eIF2a [ER stress]
Under conditions of eIF2α phosphorylation, a subset of mRNAs with small upstream open reading frames (such as activating transcription factor 4 [ATF4]) or internal ribosome entry sites are preferentially translated. ATF4 is a bZIP transcription factor that controls the regulation of expression of pro-survival UPR-target genes (e.g., the chaperones glucose regulated protein [GRP]78 and GRP94) as well as genes involved in other functions such as redox homeostasis, amino acid metabolism, apoptosis, and autophagy.
IGFBP1 activation is a subtype of molecular activation: A process that changes the activity of the IGFBP1 (Insulin Like Growth Factor Binding Protein 1) to be higher. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Endoplasmic reticulum stress induction of insulin-like growth factor-binding protein-1 involves ATF4. Mutation of the ATF4 led to the loss of IGFBP-1 regulation. Increased secretion of IGFBP-1 during hepatic ER stress may thus constitute a signal to modulate cell growth and metabolism and induce a systemic adaptive response.
Expression of CCL2 is a subtype of inflammatory cytokine gene expression: A process that convert a CCL2 (C-C Motif Chemokine Ligand 2) gene's sequenes into a mature gene prduct(s), i.e., (m)RNA, or protein. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
ATF6 activation is a subtype of molecular activation: A process that changes the activity of the ATF6 (Activating Transcription Factor 6) to be higher. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Deacreasing velocity is a subtype of changing velocity: A process that changes the velocity of the object to be slower.
PERK dimerization is a subtype of protein dimerization: The formation of a PERK dimer, a macromolecular structure consists of two noncovalently associated identical or nonidentical subunits.
PERK dimerization is a subtype of protein dimerization: The formation of a PERK dimer, a macromolecular structure consists of two noncovalently associated identical or nonidentical subunits. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Hypofunction of cholesterol transport is a subtype of hypofunction of transport: A process that performs a decreased or insufficient cholesterol transport.
Bile acids repress the transcription of cytochrome P450 7A1 (CYP7A1), which catalyzes the rate-limiting step in bile acid biosynthesis. FXR induces expression of SHP-1, a member of the nuclear receptor family that lacks a DNA-binding domain. SHP-1 represses expression of CYP7A1 by inhibiting the activity of liver receptor homolog 1 (LRH-1).
RXR heterodimers regulates absorption and ABC1-mediated efflux of cholesterol. Oxysterol receptors (LXRs) and the bile acid receptor (FXR) are the RXR heterodimer by regulating expression of the reverse cholesterol transporter, ABC1, and the enzyme of bile acid synthesis, CYP7A1, respectively.
Hypofunction of cholesterol transport from lysosome is a subtype of hypofunction of transport: A process that performs a decreased or insufficient cholestsrol transport from lysosomes. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
hypofunction of cholesterol transport from lysosome [Phospholipidosis (severe) ]
ATF6 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the ATF6 (activating transcription factor 6). ATF6 generally plays a endoplasmic reticulum membrane stress sensor role. This entity is a specific course-dependent process. This process can constitute the course of ATF6 pathway.
ATF6 signaling (primitive) [ATF6 pathway]
ATF6 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the ATF6 (activating transcription factor 6). ATF6 generally plays a endoplasmic reticulum membrane stress sensor role. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
IRE1 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the IRE1 (Inositol-requiring transmembrane kinase/endonuclease). IRE1 generally plays a endoplasmic reticulum membrane stress sensor role.
IRE1 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the IRE1 (Inositol-requiring transmembrane kinase/endonuclease). IRE1 generally plays a endoplasmic reticulum membrane stress sensor role. This process is dependent on the refolding and can constitute the course of ER stress.
IRE1 signaling (primitive) [ER stress - refolding]
Translational attenuation is a regulatory mechanism analogous to ribosome-mediated transcriptional attenuation. the system requires the presence of a short orf, called a leader peptide, encoded in the mrna upstream of the ribosome-binding site and start codon of the gene whose translation is to be regulated. certain conditions, such as presence of the antibiotic tetracycline in bacteria or amino acid starvation, may cause slowing or stalling of the ribosome translating the leader peptide. the stalled ribosome masks a region of the mrna and affects which of two alternative mrna folded structures will form, therefore controlling whether or not a ribosome will bind and initiate translation of the downstream gene. translational attenuation is analogous to ribosome-mediated transcriptional attenuation, in which mrna remodeling caused by ribosome stalling regulates transcriptional termination rather than translational initiation. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
General protein translation is inhibited via the PERK pathway to reduce increased protein burden in the ER.
ER stress increases PERK's protein-kinase activity and PERK phosphorylates eIF2alpha on serine residue 51, inhibiting translation of messenger RNA into protein. These properties implicate PERK in a signalling pathway that attenuates protein translation in response to ER stress.
Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature: 1999, 397(6716);271-4
XBP1 activation is a subtype of activation of transcription factor: A process that changes the activity of XBP1 (X-Box Binding Protein 1) to be higher.
The sodium-independent portion of bile salt uptake is mediated by OATPs (organic anion transporting polypeptides). OATP1B1 (SLCO1B1), OATP1B3 (SLCO1B3), and OATP2B1 (SLCO2B1) are expressed at the basolateral plasma membrane of hepatocytes, although OATP2B1 appears not to be a bile Salt transporter.
XBP1 splicing is a subtype of removing: The process of removing sections of the XBP1 RNA transcript to remove sequences.
XBP1 splicing is a subtype of removing: The process of removing sections of the XBP1 RNA transcript to remove sequences. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
ERAD related gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature ER-associated degradation (ERAD) gene product or products (proteins or RNA).
ERAD related gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature ER-associated degradation (ERAD) gene product or products (proteins or RNA). This entity is a specific course-dependent process. This process can constitute the course of ER stress.
ERAD related gene expression [ER stress]
IRE1 activation is a subtype of molecular activation: A process that changes the activity of the IRE1 to be higher.
IRE1 activation is a subtype of molecular activation: A process that changes the activity of the IRE1 to be higher. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Hypofunction of endosome to lysosome transport of low-density lipoprotein particle is a subtype of hypofunction of cholesterol transport: A process that performs a decreased or insufficient endosome to lysosome transport of low-density lipoprotein particle.
decreasing endosome to lysosome transport of LDL
hypofunction of endosome to lysosome transport of low-density lipoprotein particle
Ischemia is a changing process to lack enough to blood supply. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Starvation is a subtype of depleting: A process that lessens markedly in quantity of the nourishment. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Increasing demand for response to ER stress is a subtype of increasing the demand for response to stress: A process that changes the functional demand for the response to the edoplasmic reticulum (ER) stress to be higher. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
increasing demand for response to ER stress [ER stress]
Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stress acting at the endoplasmic reticulum. ER stress usually results from the accumulation of unfolded or misfolded proteins in the ER lumen. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
response to endoplasmic reticulum stress [ER stress]
Hepatocyte cell division is a subtype of cell division: The process resulting in division and partitioning of components of a heoatocyte cell to form more cells. This entity is a specific course-dependent process. This process can constitute the course of Hypertrophy.
Supplying from stored substance(s) is a subtype of making existence: A process that supplies (the stored) objects to the output.
A process of supplying the operand from the stored substances
PERK autophosphorylation is a subtype of protein autophosphorylation: The phosphorylation by PERK of one or more of its own amino acid residues (cis-autophosphorylation), or residues on PERK (trans-autophosphorylation).
Removing phospholipid by Kupffer cell or macrophage is a subtype of removing: A process that takes dead cells from a cell by Kupffer cells or macrophages .
Removing dead cell by Kupffer cell or macrophage
Increasing number of stress responses is a subtype of increasing number of actions: A process that becomes larger in the number of stress responses. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
increasing number of stress responses [ER stress]
Moving drug to the inside of liver is a subtype of moving A to the inside of B: A process that of the movement of drug into hepatocytes. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
moving drug to hepatocyte [Eosinophilic granular degeneration]
Increasing demand for protein quality control is a subtype of increasing functional demand: A process that changes the functional demand for the protein quality control to be higher.
increasing demand for protein quality control
Increasing demand for protein quality control is a subtype of increasing functional demand: A process that changes the functional demand for the protein quality control to be higher. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
increasing demand for protein quality control [ER stress]
Cholestasis dependent chemical compound is a subtype of toxic course dependent chemical entity. This entity (drug) can participate in the course of cholestasis.
Endoplasmic reticulum dysfunction is a subtype of dysfunctioning: A process that performs an abnormal and incomplete endoplasmic reticulum function.
Endoplasmic reticulum dysfunction is a subtype of dysfunctioning: A process that performs an abnormal and incomplete endoplasmic reticulum function. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
endoplasmic reticulum dysfunction [ER stress]
ER stress dependent molecule is a subtype of toxic course dependent chemical entity. This gene can participate in the course of ER stress as a gene product. Gene profile:Rat/Liver/
CHOP->NfKB->CXCL10->inflammation in beta cells PMID:22653339
CHOP Knock down resulted in reduced cytokine-induced NF-κB activity and expression of key NF-κB target genes involved in apoptosis and inflammation, including iNOS, FAS, IRF-7, IL-15, CCL5 and CXCL10.
Any process that modulates the frequency, rate or extent of lysophagy.
Any process that activates, maintains or increases the rate of lysophagy.
A pathologic process that involves the transformation of normal cells to a neoplastic state and resulting in polyclonal or monoclonal neoplastic cell proliferation. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
ER stress-induced inflammation: does it aid or impede disease progression?
Critical role of XBP1 in cancer signalling is regulated by PIN1.
A role played by the entity that activates the activity of tumor cells.
Inflammatory response is a subtype of changing material: The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Endoplasmic reticulum stress and related signaling networks, (adipo)cytokines, and innate immunity are emerging as central pathways that regulate key features of NASH.
Inflammation Preceding Steatosis. Simple hepatic steatosis, which is benign and nonprogressive in the majority of patients, and NASH may reflect different disease entities. Inflammation results in a stress response of hepatocytes, may lead to lipid accumulation, and therefore could precede steatosis in NASH.
Hepatic inflammation improves glucose homeostasis through IKKβ-XBP1s Interaction.
NfkB signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transduced with the regulation of transcription of target genes by NF-kappaB.
NfkB signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transduced with the regulation of transcription of target genes by NF-kappaB. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Bone-marrow-derived inhibitory cell migration is a moving process of bone-marrow-derived inhibitory cell to inflammatory site.
bone-marrow-derived inhibitory cell migration
The orderly movement of a macrophage from one site to another. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Generating motion is a subtype of generating: A process that generates the directed movement.
Tumor growth is a subtype of cell growth: The process in which a tumor cell increases in size.
Tumor growth is a subtype of cell growth: The process in which a tumor cell increases in size. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
A J-Protein Co-chaperone Recruits BiP to Monomerize IRE1 and Repress the Unfolded Protein Response.
oxidative stress ->oxidized lipids production ->ER stress induction (PERK(->eIF2a), JNK)->activation of autophagy->HO-1activation->cell survival Oxidized lipids activate autophagy in a JNK-dependent manner by stimulating the endoplasmic reticulum stress response. HNE modification of ER proteins results in the activation of the adaptive arm of the unfolded protein response. This HNE-mediated response is characterized by the phosphorylation of PERK, eIF2α, and JNK, activation of autophagy, and the induction of HO-1. HNE-stimulated conversion of LC3 (an essential step in autophagosome formation and marker of autophagy) and HO-1 induction is shown to be mediated by ER stress via JNK activation. PMID:24024137
The basal level of heme oxygenase expression in the skin may serve as a first protective environment against acute oxidative and inflammatory insults.
JNK signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the JNK (a stress-activated protein kinase (SAPK) ).
JNK signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the JNK (a stress-activated protein kinase (SAPK) ). This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Cell Metab. 2006 Oct;4(4):263-73. Transcriptional control of adipocyte formation.
Tumor necrosis factor-alpha causes insulin receptor substrate-2-mediated insulin resistance and inhibits insulin-induced adipogenesis in fetal brown adipocytes. The antiadipogenic effect of TNF-alpha was accompanied by a down-regulation of CCAAT/enhancer-binding protein-alpha and beta mRNAs and up-regulation of CCAAT/enhancer-binding protein-delta, with the expression of peroxisome proliferator-activated receptor-gamma remaining essentially unmodified.
Drug-, radiation-induced, or spontaneous injuries to DNA that introduce deviations from its normal double-helical conformation. These changes include structural distortions that interfere with replication and transcription, as well as point mutations that disrupt base pairs and exert damaging effects on future generations through changes in DNA sequence. If the damage is minor, it can often be repaired (DNA repair); extensive damage can induce apoptosis. The degree is severe. This entity is a specific course-dependent process. This process can constitute the course of necrosis.
Phospholipase A2 Group XV [Phospholipidosis]
Group XV phospholipase A2, a lysosomal phospholipase A2. Lysosomal phospholipase A2 (LPLA2) , group XV phospholipase A2. LPLA2 is highly expressed in alveolar macrophages. A marked accumulation of glycerophospholipids and extensive lamellar inclusion bodies, a hallmark of cellular phospholipidosis, is observed in alveolar macrophages in LPLA2(-/-) mice. This defect can also be reproduced in macrophages that are exposed to cationic amphiphilic drugs such as amiodarone. In addition, older LPLA2(-/-) mice develop a phenotype similar to human autoimmune disease.
This gene is a member of the insulin-like growth factor binding protein (IGFBP) family and encodes a protein with an IGFBP domain and a thyroglobulin type-I domain. The protein binds both insulin-like growth factors (IGFs) I and II and circulates in the plasma. Binding of this protein prolongs the half-life of the IGFs and alters their interaction with cell surface receptors. [provided by RefSeq, Jul 2008]
Endoplasmic reticulum stress induction of insulin-like growth factor-binding protein-1 involves ATF4.
LY2090314, a glycogen synthase kinase-3 (GSK-3) inhibitor, specifically suppressed constitutive expression of the CYP2B6 gene, which is at least partially explained by direct CAR inhibition.
β-Arrestin 2 Promotes Hepatocyte Apoptosis by Inhibiting Akt Protein: The protective effect of deficiency of Arrb2 is due to loss of negative regulation of Akt due to BDL and decreased downstream GSK3β and p38 MAPK signaling pathways.
β-Arrestin 2 Promotes Hepatocyte Apoptosis by Inhibiting Akt Pathway in Alcoholic Liver Disease.
TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin by liver. Science 300: 1574-1577, 2003.
TRB3 is a novel target of CHOP/ATF4 and downregulates its own induction by repression of CHOP/ATF4 functions, and that it is involved in CHOP-dependent cell death during ER stress.
TRB3 inhibits the transcriptional activation of stress-regulated genes by a negative feedback on the ATF4 pathway.
Any process that stops, prevents, or reduces the frequency, rate or extent of protein kinase B signaling, a series of reactions mediated by the intracellular serine/threonine kinase protein kinase B. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
negative regulation of AKT signaling [Ground glass appearance]
Malfunction of mitochondria is a subtype of malfunctioning process: A process that cannot perform a mitochondrial function appropriately or cannot realize it at all.
Arrb2 -inactivation (mouse)[Ground glass appearance]
G protein-coupled receptor class C group 5 member B
BOSS was expressed in the fat body, a nutrient-sensing tissue equivalent to mammalian liver and adipose tissues, and in photoreceptor cells. Boss null mutants had small bodies, exhibited abnormal sugar and lipid metabolism (elevated circulating sugar and lipid levels, impaired lipid mobilization to oenocytes), and were sensitive to nutrient deprivation stress. Because human G protein-coupled receptor 5B and the seven-transmembrane domain of BOSS share the same sequence, our results also have important implications for glucose metabolism in humans.
GPRC5B activates obesity-associated inflammatory signaling in adipocytes: GPRC5B-deficient mice were protected from diet-induced obesity and insulin resistance because of reduced inflammation in their white adipose tissue.
Intercellular transfer of GPRC5B via exosomes drives HGF-mediated outward growth.
Drug-induced steatosis is mainly caused by compounds such as 4,4′- diethylaminoethoxyhexestrol, amiodarone, tamoxifen, perhexiline, etc., which accumulate in mitochondria and inhibit β-oxidation and mitochondrial respiration. Casarett & Doull's Toxicology: The Basic Science of Poisons, Eighth Edition
Types of hepatobiliary injury: Fatty liver: Amiodarone, CCl4, ethanol, fialuridine, tamoxifen, valproic acid. Casarett & Doull's Toxicology: The Basic Science of Poisons, Eighth Edition
Increasing demand for drug metabolism is a subtype of increasing functional demand: A process changes the functional demand for the for drug metabolism to be higher.
Elucidation of a novel phenformin derivative on glucose-deprived stress responses in HT-29 cells. 2-(2-chlorophenyl)ethylbiguanide (2-Cl-Phen) down-regulated expression of several ER stress-related genes, with the exception of GADD153. The expression levels of ATF6α, GRP78, MANF, and CRELD2 mRNA were almost completely decreased by 2-Cl-Phen.
Armet/Manf and Creld2 are components of a specialized ER stress response provoked by inappropriate formation of disulphide bonds: implications for genetic skeletal diseases.
Endoplasmic reticulum (ER) stress inducible factor cysteine-rich with EGF-like domains 2 (Creld2) is an important mediator of BMP9-regulated osteogenic differentiation of mesenchymal stem cells. (
TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death.
ER stress dependent molecule is a subtype of toxic course dependent chemical entity. This gene can participate in the course of ER stress as a gene product. Gene profile:Human/in vitro/Hepatocyte/
ER stress dependent molecule (human in vitro)
ER stress dependent chemical entity is a subtype of toxic course dependent chemical entity. This entity can participate in the course of ER stress.
A laboratory test or analysis of the biological activity of a substance performed by studying its effect in an experimental situation outside the human, e.g. in the test tube rather than in living systems.
ER stress and PPARα activation contribute to carcinogenesis in a fatty liver. PMID:22009939 Hepatosteatosis in peroxisome deficient liver despite increased beta-oxidation capacity and impaired lipogenesis. Biochimie (2011) 93:1828–38. FGF21-FGFR1 coordinates phospholipid homeostasis, lipid droplet function and ER stress in obesity.Endocrinology. 2016 PMID:27690692 Fibroblast growth factor 21 (FGF21) is an endocrine growth factor, a regulator of fatty acids and glucose metabolism. Recently, it has been reported that FGF21 expression is regulated by activating transcription factor 4 (ATF4), a transcription factor activated by various stimuli such as endoplasmic reticulum (ER) stress. PMID:27010621 Endoplasmic reticulum stress induces up-regulation of hepatic beta-Klotho expression through ATF4 signaling pathway. PMID:25727012
Endocrine regulation of the fasting response by PPARα-mediated induction of fibroblast growth factor 21: FGF21 is induced directly by PPARalpha in liver in response to fasting and PPARalpha agonists. FGF21 in turn stimulates lipolysis in white adipose tissue and ketogenesis in liver. PPARalpha-FGF21 endocrine signaling pathway in regulating diverse metabolic and behavioral aspects of the adaptive response to starvation.
ER stress and PPARα activation contribute to carcinogenesis in a fatty liver.
FGF21 expression is regulated by activating transcription factor 4 (ATF4), a transcription factor activated by various stimuli such as endoplasmic reticulum (ER) stress.
FGF21 is regulated by PPARa: Hepatic fibroblast growth factor 21 is regulated by PPARα and is a key mediator of hepatic lipid metabolism in ketotic states.
Any process that activates, maintains or increases the rate of lysophagy. This entity is a specific course-dependent process. This process can constitute the course of phospholipidosis.
positive regulation of lysophagy [Phospholipidosis]
MANF is upregulated in ER stress in vitro and protect cells from ER stress-induced cell death in vivo.
mesencephalic astrocyte-derived neurotrophic factor [ER stress]
Armet, a UPR-upregulated protein, inhibits cell proliferation and ER stress-induced cell death. Armet/MANF protein was upregulated by various forms of ER stress in several cell lines as well as by cerebral ischemia of rat. Armet/MANF was localized in the ER and Golgi and was also a secreted protein. Silencing Armet/MANF by siRNA oligos in HeLa cells rendered cells more susceptible to ER stress-induced death, but surprisingly increased cell proliferation and reduced cell size.
Mesencephalic astrocyte-derived neurotrophic factor (MANF) has a unique mechanism to rescue apoptotic neurons.
MANF deficiency results in pancreatic beta cell depletion and diabetes in mice. MANF is highly expressed in mouse and human islet beta cells and exocrine acinar cells. MANF deficiency leads to ER stress and chronic unfolded protein response in beta cells. MANF protein enhances proliferation of beta cells in vitro and in vivo in diabetic mice.
Permeating mitochondrial membrane is a subtype of moving. A process that change the location of the operand thorough mitochondrial membrane.
DNAJB9 - chaperone -vitro (human)[ER stress]
Toxicol Pathol. 2013 Feb;41(2):235-62. doi: 10.1177/0192623312470764. Epub 2013 Jan 18. Xenobiotic perturbation of ER stress and the unfolded protein response.
Increasing demand for drug metabolism is a subtype of increasing functional demand: A process changes the functional demand for the for drug metabolism to be higher. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
increasing demand for drug metabolism [Ground glass appearance]
A role played by molecules that catalysis of the cleavage of a C-C bond in a molecule containing a hydroxyl group and a carbonyl group to form two smaller molecules, each being an aldehyde or a ketone.
The endoplasmic reticulum sulfhydryl oxidase Ero1-beta drives efficient oxidative protein folding with loose regulation.
Xenobiotic perturbation of ER stress and the unfolded protein response.
Deregulation of Pancreas-Specific Oxidoreductin ERO1β in the Pathogenesis of Diabetes Mellitus
This gene encodes a member of the gamma-glutamylcyclotransferase family of proteins. The encoded protein has been shown to promote neuronal differentiation by deglycination of the Notch receptor, which prevents receptor maturation and inhibits Notch signaling. This protein may also play a role in the unfolded protein response, and in regulation of glutathione levels and oxidative balance in the cell. Elevated expression of this gene may indicate increased risk of cancer recurrence among breast and ovarian cancer patients. [provided by RefSeq, Sep 2016]
CHAC1/MGC4504 is a novel proapoptotic component of the unfolded protein response, downstream of the ATF4-ATF3-CHOP cascade. Acts as a pro-apoptotic component of the unfolded protein response pathway by mediating the pro-apoptotic effects of the ATF4-ATF3-DDIT3/CHOP cascade.
Mammalian proapoptotic factor ChaC1 and its homologues function as γ-glutamyl cyclotransferases acting specifically on glutathione. Glutathione depletion is an important factor for apoptosis initiation and execution (
Human CHAC1 Protein Degrades Glutathione, and mRNA Induction Is Regulated by the Transcription Factors ATF4 and ATF3 and a Bipartite ATF/CRE Regulatory Element.
Toxic course dependent process is a subtype of primitive process: A process that can constitute the disease course.
Insulin resistance (process) is a subtype of decreasing sensitivity: A process that changes the sensitivity to the circulating insulin to be lower. This entity is a specific course-dependent process. This process can constitute the course of NASH.
Insulin resistance alters hepatic ethanol metabolism: studies in mice and children with non-alcoholic fatty liver disease.
ER stress dependent molecule is a subtype of toxic course dependent chemical entity. This gene can participate in the course of ER stress as a gene product. Gene profile:Mouse//Liver/
Tumor cell survial is a subtype of keeong quantity: A process that keeps the viability of a tumor cell. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
tumor cell survial [Glutathione depletion]
Any biological process that results in permanent cessation of all vital functions of a cell. This entity is a specific course-dependent process. This process can constitute the course of Oxidative stress.
Inflammatory response is a subtype of changing material: The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages. This entity is a specific course-dependent process. This process can constitute the course of Oxidative stress.
Inflammatory response [Oxidative stress]
Hepatic fibrosis is a subtype of fibrosis: A process that replaces liver tissues to fibrous connective tissues, usually as a consequence of inflammation or other injury.
Hepatic fibrosis is a subtype of fibrosis: A process that replaces liver tissues to fibrous connective tissues, usually as a consequence of inflammation or other injury. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Protein production is a subtype of making existence: Aprocess that makes existent of a protein due to biosynthesis or secretion resulting in an increase in its levels. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Membrane protein production is a subtype of protein production: A process that makes existent of a membrane protein due to biosynthesis, secretion, or membrane trafficking, resulting in an increase in its levels.
Lysosome homeostasis is a subtype of homeostatic process: A process that that preserves a lysosome in a stable functional or structural state. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
Decreasing amount of xenobiotics is a subtype of decreasing quantity: A process that changes the quantity of xenobiotics to be lower.
A role of combining with a signal and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity by catalysis of the reaction: ATP + a protein-L-tyrosine = ADP + a protein-L-tyrosine phosphate.
transmembrane receptor protein tyrosine kinase
IRE - stress sensor (canonical)[ER stress -Refolding]
A physical attribute inhering in a bearer by virtue of the bearer's function.
Negative regulation of phospholipase A2 mediated phospholipid degradation is a subtype of negative regulation of phospholipid degradation: A process that stops, prevents, or reduces the frequency, rate or extent of phospholipase A2 mediated phospholipid degradation.
negative regulation of phospholipase A2 mediated phospholipid degradation
HSP90B1 - chaperone -vitro (human)[ER stress]
IL-2 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the cytokine IL-2.
The multiplication or reproduction of cells, resulting in the rapid expansion of a cell population. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
A role played by the entity which inhibits the process of cell death.
IL-2 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the cytokine IL-2. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense) .
IL-2 signaling (primitive) [Phospholipidosis (excessive defense) ]
Blimp-1 is also crucial for inducing cytokine production by inflammatory T helper cells and effector Treg cells. The gene encoding IL-2 is one of the most important genes targeted by Blimp-1 in T cells, because IL-2 production is indispensable for T cell proliferation and differentiation
Eosinogranular degeneration dependent chemical entity is a subtype of toxic course dependent chemical entity. This entity can participate in the course of eosinogranular degeneration.
eosinogranular degeneration dependent chemical entity
Tumor cell survial is a subtype of cell survival: A process that keeps the viability of a tumor cell. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense).
tumor cell survial [Phospholipidosis (excessive defense)]
Liver cacer dependent gene is a subtype of toxic course dependent chemical entity. This gene can participate in the course of liver cancer as a gene product.
Cell death dependent chemical entity is a subtype of toxic course dependent chemical entity. This entity can participate in the course of cell death.
Cell death dependent molecule is a subtype of toxic course dependent chemical entity. This gene can participate in the course of cell death as a gene product. Gene profile:Rat/Liver/
Cell death dependent molecule is a subtype of toxic course dependent chemical entity. This gene can participate in the course of cell death as a gene product. Gene profile:Human/in vitro/Hepatocyte/
cell death dependent molecule (human in vitro)
Increasing liver weight is a subtype of increasing weight: A process that changes the weight of the liver to be higher. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense).
increasing liver weight [Phospholipidosis (excessive defense)]
Mol Cell Biol. 1998 Oct;18(10):6063-74. FGF-18, a novel member of the fibroblast growth factor family, stimulates hepatic and intestinal proliferation. FGF-18 is highly conserved between humans and mice and is most homologous to FGF-8 among the FGF family members. The two tissues which appeared to be the primary targets of FGF-18 were the liver and small intestine, both of which exhibited histologic evidence of proliferation and showed significant gains in organ weight following 7 (sometimes 3) days of FGF-18 treatment. Transgenic mice that overexpressed FGF-18 in the liver also exhibited an increase in liver weight and hepatocellular proliferation. These results suggest that FGF-18 is a pleiotropic growth factor that stimulates proliferation in a number of tissues, most notably the liver and small intestine.
Inflammatory cytokine gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature inflammatory cytokine gene product or products (proteins or RNA). This entity is a specific course-dependent process. This process can constitute the course of Oxidative stress.
inflammatory cytokine gene expression [Oxidative stress].
Inflammasome activation is a subtype of activating: A process that changes the activity of the inflammasome, to be higher. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
inflammasome activation [Glutathione depletion]
HMGB1 promotes ductular reaction and tumorigenesis in autophagy-deficient livers:HMGB1 was released from autophagy-deficient hepatocytes independently of cellular injury but depended on NRF2 and the inflammasome, which was activated by NRF2.
Acot5 (mouse)[Eosinophilic granular degeneration]
Mouse ACOTs 3–6 and human ACOT4 contain functional type 1 peroxisome targeting sequences at their C-termini. ACOT3 and ACOT5 are not present in human, however, human ACOT4 is active towards both short-chain dicarboxylyl-CoAs (e.g. succinyl-CoA) and medium- to long-chain acyl-CoAs and thereby combining activities of ACOTs 3–5.
Increasing demand for glutathione conjugation is a subtype of increasing functional demand: A process changes the functional demand for the for glutathione conjugation to be higher.
increasing demand for glutathione conjugation
NRF2 -inflammasone activator (canonical)[Glutathione depletion]
A role played by the entity which positive regulates the inflammasone activity.
Increasing ALT concentration in blood is a subtype of increasing concentration: A process that changes the alanine aminotransferase (ALT) concentration to be higher.
This entity is a role in which a process plays an essential role in the course of toxicity manifestation.
NRF2 -antioxidant (canonical)[Glutathione depletion]
Catalysis of the reaction: (5-L-glutamyl)-peptide + an amino acid = peptide + 5-L-glutamyl-amino acid.
The mammlian enzyme is part of the cell antioxidant defense mechanism. It initiates extracellular glutathione (GSH) breakdown, provides cells with a local cysteine supply and contributes to maintain intracelular GSH levels. The protein also has EC 3.4.19.13 (glutathione hydrolase) activity [3-4]. The enzyme consists of two chains that are created by the proteolytic cleavage of a single precursor polypeptide. The N-terminal L-threonine of the C-terminal subunit functions as the active site for both the cleavage and the hydrolysis reactions
Increasing γ-glutamyltransferase concentration in blood is a subtype of increasing concentration: A process that changes the γ-glutamyltransferase (GGT) concentration to be higher. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
increasing γ-glutamyltransferase concentration in blood [Lipidosis]
Increasing ALT concentration in blood is a subtype of increasing concentration: A process that changes the alanine aminotransferase (ALT) concentration to be higher. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
increasing blood GPT concentration [lipidosis]
increasing blood ALT concentration [lipidosis]
Increasing AST concentration in blood is a subtype of increasing concentration: A process that changes the aspartate amino transferase (AST) concentration to be higher. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
inreasing blood GOT concentration [lipidosis]
increasing blood AST concentration [lipidosis]
Leaking content from cell is a subtype of leaking: A process that leaks contents from the cell. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
A concentration attribute inhering in a bearer by virtue of the bearer's exhibiting concentration.
Malfunctioning of mitochondrial ATP synthesis coupled electron transferr is a subtype of malfunctioning process: A process that cannot perform a respiratory electron transport chain appropriately or cannot realize it at all. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
mitochondrial respiratory chain abnormality [Mitochondrial disorder]
Experimental investigations also pointed to a progressive reduction of MRC activity during NAFLD, which could impair energy output and aggravate ROS overproduction by the damaged MRC. It is likely that this event triggers a vicious cycle since mitochondrial ROS are able to oxidatively damage nearby MRC enzymes and mtDNA. Other mechanisms leading to impaired MRC activity could include higher levels of different lipid intermediates including free FAs, increased generation of lipid peroxidation products such as 4‐HNE, and reduced adiponectin action. Several MRC complexes including COX are sensitive to ROS and RNS. In addition, COX can be inhibited by low levels of NO and inactivated by 4‐hydroxynonenal (4‐HNE), a reactive aldehyde generated during lipid peroxidation. Some lipid derivatives such as FAs can directly inhibit several enzymes involved in MRC and OXPHOS.
iNOS induction is linked to alterations in the NO-dependent control of mitochondrial respiration (at the level of cytochrome c oxidase), which potentially contributes to the development of alcoholic steatohepatitis. Thus, the CL-dependent alterations of the ETC organization in supercomplexes could be another factor contributing to ROS generation and to mitochondrial bioenergetic decay in NAFLD. Another consequence of cytochrome c release from mitochondria is that it interferes with electron transport through ETC, resulting in ROS formation and triggering a new vicious cycle, which will worsen the disturbance.
Bellanti et al. showed through targeted lipidomic analysis that rats fed diets rich in cholesterol exhibited increased toxic hepatic triol, which induces apoptosis and impaired mitochondrial respiration in vitro.
Recent study has found that hepatic fatty acid accumulation can cause damaged mitochondria accumulation, which can impair mitochondrial respiratory chain function and fatty acid oxidative degradation.
Acot8 (mouse)[Eosinophilic granular degeneration]
human ACOT8 in human and murine cell lines as well as in transgenic mice was associated with peroxisome proliferation and increased lipid accumulation (determined as number of lipid droplets)
Fatty acid metabolic enzyme acyl-CoA thioesterase 8 promotes the development of hepatocellular carcinoma.
ACOT8 is a peroxisomal protein with broad substrate specificity, including medium-to long-chain and methyl branched acyl-CoAs, intermediates of beta-oxidation and bile acid-CoA. The activity is inhibited by CoA and expression is upregulated by fasting and PPARα activation and ACOT8 overexpression leads to peroxisomal proliferation in murine and human cell lines.
ER stress dependent molecule is a subtype of toxic course dependent chemical entity. This gene can participate in the course of ER stress as a gene product. Gene profile:caonical that described in textbooks or articles.
ER stress dependent molecule (canonical)
Dissociation of Bip complex is a subtype of detaching: A process that disaggregates a Bip complex into Bip and other molecule(s).
Negative regulation of endoplasmic reticulum-associated degradation is a subtype of negative regulation of protein catabolic process: A process that stops, prevents, or reduces the frequency, rate or extent of endoplasmic reticulum-associated degradation.
negative regulation of endoplasmic reticulum-associated degradation
IRE - stress sensor (canonical)[ER stress -ERAD]
A role played by the entity which interferes with the activity of PERK.
Drug-induced steatosis is mainly caused by compounds such as amiodarone, tamoxifen, which accumulate in mitochondria and inhibit β-oxidation and mitochondrial respiration. Casarett & Doull's Toxicology: The Basic Science of Poisons, Eighth Edition
A role played by the entity which receives some stress and transmits operand(s).
A role played by the entity which receives a stimulus and transmits operand(s).
negative regulation of immune response is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of the immune response.
Hyperfunction of dead cell phagocytosis by Kupffer cells is a subtype of hyperfunctioning: A process that performs phagocytosis of dead cells by Kupffer cells or macrophages execessively.
hyperfunction of dead cell phagocytosis by Kupffer cells (macrophages)
A role of the entity which carries substances between the nucleus and the cytoplasm of a cell by moving along with the target protein.
Gene expression regulation system is a subtype of pathway system. This entity has sub-parts and has a goal of regulating gene expressions as a systemic context.
Lipidosis (toxic course) is a subtype of process sequences: The courses of processes through which lipidosis is realized via lipid homeostasis imbalance.
Fatty liver (steatosis) is defined biochemically as an appreciable increase in the hepatic lipid (mainly triglyceride) content, which is <5 wt% in the normal human liver.
Glutathione depletion dependent process is a subtype of toxic course dependent process: A process that can constitute the course of glutathione depletion .
Hyperfunction of fatty acid biosynthesis is a subtype of hyperfunction of biosynthesis: A process that performs an excessive fatty acid biosynthesis. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
hyperfunction of fatty acid biosynthesis [Lipidosis]
Hypofunction of lipid degradation is a subtype of hypofunction of decomposing: A process that performs a decreased or insufficient lipid degradation. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
hypofunction of lipid degradation [Lipidosis]
Increaing in fatty acid inflow into hepatocyte is a subtype of increasing quantity: A process that changes the fatty acid inflow into the hepatocyte to be larger. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
increaing in fatty acid inflow into hepatocyte [Lipidosis]
Lipid metabolism imbalance is a subtype of imbalance: A process that becomes lacking a homeostastasis balance of lipid metabolism. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
CASP1 (predicted)(human)[Glutathone depletion]
GSH regulates protein secretion, driving tumor necrosis factor α release, hypoxia-inducible factor-1α stability, STAT3 phosphorylation, and caspase-1 activation in macrophages.
The findings in Atg7ΔHep/Casp1-/- mice were consistent with those from studies of Atg7ΔHep/Nrf2-/- mice and Atg7ΔHep/Hmgb1-/- mice, suggesting that the inflammasome was activated by NRF2, which in turn caused HMGB1 release and DR but not other pathologies. Indeed, we found that the expression of Caspase-1 but not that of IL-1β and IL-18 were elevated in autophagy-deficient livers in a NRF2-dependent manner, supporting the above hypothesis and implying the more specific role of CASPASE-1 in HMGB1 release but not in IL-1β nor IL-18 release in the autophagy deficient setting.
The involvement of caspase-1 in the apoptosis cascade suggests that TNF-α and FasL may be exerting a direct injurious effect on hepatocytes, as well as activating and recruiting inflammatory cells.
A sheet or layer to separate or connect between biological structures.
Deacreasing flow velocity is a subtype of changing flow: A process that changes the velocity of the object to be slower.
Lipid storage in liver is a subtype of lipid storage: The accumulation and maintenance in cells or tissues of lipids in the liver. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
Hyperfunction of lipid biosynthesis is a subtype of hyperfunction of biosynthesis: A process that performs an excessive lipid biosynthesis. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
hyperfunction of lipid biosynthesis [Lipidosis]
Hyperfunction of lipid synthetic gene expression is a subtype of hyperfunction of gene expression: A process that performs an excesssive lipid biosynthetic gene expression. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
hyperfunction of lipid synthetic gene expression [Lipidosis]
The chemical reactions and pathways involving alcohols, any of a class of compounds containing one or more hydroxyl groups attached to a saturated carbon atom. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
Hypofunction of mitochondrial fatty acid beta-oxidation is a subtype of hypofunction of fatty acid beta-oxidation: A process that performs a decreased or insufficient fatty acid beta-oxidation. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
hypofunction of mitochondrial fatty acid beta-oxidation [Lipidosis]
Changing abnormal cellular structure is a subtype of changing structure: A process that changes the structure of the cell abnormally. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
changing abnormal cellular structure [Phospholipidosis]
Increasing phospholipid inflow (severe) is a subtype of increase in phospholipid inflow: A process that changes the phospholipid inflow into the hepatocyte to be larger. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
increasing phospholipid inflow (severe) [Phospholipidosis (severe) ]
NRF2 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal transmitted by the NRF2. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
NRF2 signaling (primitive) [Glutathione depletion]
Negative regulation of phospholipid degradation is a subtype of negative regulation of decomposing: A process that stops, prevents, or reduces the frequency, rate or extent of phospholipid degradation. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
negative regulation of phospholipid degradation [Phospholipidosis]
IRE - stress sensor (canonical)[ER stress - apotosis]
Phospholipid homeostasis imbalance is a subtype of lipid homeostasis imbalance: A process that becomes lacking a phospholipid homeostastasis balance. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
phospholipid homeostasis imbalance [Phospholipidosis]
Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of phospholipids. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
hyperfunction of phospholipid biosynthesis [Phospholipidosis]
Increasing demand for phospholipid degradation is a subtype of increasing functional demand: A process that changes the functional demand for the phospholipid degradation to be higher. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
increasing demand for phospholipid degradation [Phospholipidosis]
Phospholipid accumulation in lysosome is a subtype of phospholipid accumulation: A process that keeps phospholipid in the lysosome. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
phospholipid accumulation in lysosome [Phospholipidosis]
Hypofunction of phospholipase transport to lysosome is a subtype of hypofunction of phospholipase transport to lysosome : A process that performs a decreased or insufficient phospholipase transport to lysosome severely. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
hypofunction of phospholipase transport to lysosome [Phospholipidosis (severe) ]
Increasing lysosomal pH is a subtype of changing pH: A process that changes the pH in lysosome to be higher. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis(severe).
increasing lysosomal pH [Phospholipidosis(severe)]
Lysosomal Re-acidification Prevents Lysosphingolipid-Induced Lysosomal Impairment and Cellular Toxicity. PMID:27977664
Forming a complex of drugs and biological substance is a subtype of protein complex assembly: The aggregation, arrangement and bonding together between drugs and biological molecules to form a complex. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (mild).
forming a complex of drugs and biological substance [Phospholipidosis (mild)]
Hypofunction of phospholipid deradation by phospholipase is a subtype of hypofunction of phospholipid degradation: A process that performs a decreased or insufficient phospholipid deradation by phospholipase. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
hypofunction of phospholipid deradation by phospholipase [Phospholipidosis]
Hyperfunction of phospholipid synthesis gene expression is a subtype of hyperfunction of gene expression: A process that performs an excesssive phospholipid synthetic gene expression. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
hyperfunction of phospholipid synthesis gene expression [Phospholipidosis]
Hyperfunction of accumulation is a subtype of hyperfunctioning: A process that performs accumulating excessively.
Undigested membrane material accumulation is a subtype of accumulation of substances in a biological object: A process that keeps undigested membrane material. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
undigested membrane material accumulation [Phospholipidosis]
Increasing number of macrophage derived foam cell is a subtype of increasing number of objects: A process that becomes larger in the number of foam cell, a type of macrophage containing lipids in small vacuoles, in the liver. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
increasing number of macrophage derived foam cell [Phospholipidosis]
Lipid homeostasis imbalance is a subtype of chemical homeostasis imbalance: A process that becomes lacking a lipid homeostastasis balance. The degree is mild. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
lipid homeostasis imbalance (mild) [Lipidosis]
Phospholipid accumulation in lysosome is a subtype of phospholipid accumulation: A process that keeps phospholipid in the lysosome. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
phospholipid accumulation in lysosome [Phospholipidosis (severe) ]
Increasing hepatocellular volume is a changing process to change the volume of the hepatocyte to increase. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense).
increasing hepatocellular volume [Phospholipidosis (excessive defense)]
Mild accumulation of abnormal proteins in ER is a subtype of accumulation of abnormal proteins in ER: A process that keeps abnormal protein(s) in the ER (endoplasmic reticulum) mildly.
mild accumulation of abnormal proteins in ER
Increasing phospholipid is a subtype of increasing quantity: A process that changes the amount of phospholipid to be larger. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
increasing phospholipid [Phospholipidosis]
PLA2G2E (human) positively regulator of immune response[Phospholipidosis]
The adipocyte-inducible secreted phospholipases PLA2G5 and PLA2G2E play distinct roles in obesity.
Hypofunction of phospholipid degradation is a subtype of hypofunction of decomposing: A process that performs a decreased or insufficient phospholipid degradation. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
hypofunction of phospholipid degradation [Phospholipidosis]
A vesicle-mediated transport process that results in the engulfment of external particulate material by phagocytes and their delivery to the lysosome. The particles are initially contained within phagocytic vacuoles (phagosomes), which then fuse with primary lysosomes to effect digestion of the particles. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
Any biological process that results in permanent cessation of all vital functions of a cell. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
Any process that activates or increases the frequency, rate or extent of cell death by apoptotic process. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense) .
positive regulation of apoptotic process [Phospholipidosis (excessive defense) ]
Sphingosine-1-phosphate lyase potentiates apoptosis via p53- and p38-dependent pathways and is down-regulated in colon cancer.
A process that becomes lacking a homeostastasis balance of the sphingomyelin metabolism in the nervous system. This entity is a specific course-dependent process. This process can constitute the course of Niemann Pick Disease Type A.
sphingomyelin metabolism imbalance in nervous system [Niemann Pick Disease Type A]
Compound accumulation in lysosome is a subtype of accumulation of xenobiotics: A process that keeps compound in the lysosome. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
compound accumulation in lysosome [Phospholipidosis]
Direct competition of troglitazone metabolites with conjugated bilirubin at the level of MRP2 could result in conjugated hyperbilirubinemia.
The directed movement of carbohydrate into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. Carbohydrates are any of a group of organic compounds based of the general formula Cx(H2O)y. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
carbohydrate transport [Ground glass appearance]
Mitochondrial dysfunction is a subtype of dysfunctioning: A process that performs an abnormal and incomplete mitochondrial function. This entity is a specific course-dependent process. This process can constitute the Mitochondrial disorder.
mitochondrial dysfunction [Mitochondrial disorder]
Furthermore, high glucose levels promote ROS overproduction within hepatocytes, thus favoring oxidative stress and mitochondrial dysfunction. NAFLD has been associated with higher hepatic expression of the inducible nitric oxide (NO) synthase (iNOS), mainly as a consequence of tumor necrosis factor‐α (TNF‐α) overproduction by the Kupffer cells. NO can readily react with the superoxide anion, thus generating the RNS peroxynitrite, which has deleterious effects on mitochondrial function and genome.
In liver cells, mitochondrial dysfunction plays a critical role by amplifying the apoptotic signal and integrating both pathways into a final common pathway. Mitochondrial dysfunction results in the release of several proapoptotic proteins into the cytosol, including cytochrome c.
Hepatocytes display an eosinophilic cytoplasm upon hematoxylin-eosin staining, reflecting abundant mitochondria. Thus, it is not surprising that mitochondrial dysfunction promotes cellular damage and is linked to liver diseases.
Strikingly, NEAT1-depleted single cell clones showed a consistent reduction in mitochondrial DNA (mtDNA) (Fig. 7a), reduced mitochondrial respiration (by detection of the oxygen consumption rate (OCR); Fig. 7b) and adenosine triphosphate (ATP) production (Fig. 7c), reduced OCR and extracellular acidification rate (ECAR) rate (Fig. 7d), suggesting that the aberrant NEAT1 expression could cause mitochondrial dysfunction.
Emerging evidence suggests that mitochondrial dysfunction or maladaptation contributes to detrimental effects on hepatocyte bioenergetics, reactive oxygen species (ROS) homeostasis, endoplasmic reticulum (ER) stress, inflammation, and cell death leading to NASH and HCC. Just like in NASH, oxidative stress, mitochondrial dysfunction, and oxidized mtDNA also contribute to the progression of HCC through influences on inflammation, cell death, and ER stress. Moreover, in vitro treatment of liver cells with saturated fatty acids (palmitic and stearic acids) reproduces mitochondrial dysfunction found in NASH, including decreasing cellular ATP content and mtDNA-encoded oxidative phosphorylation (OXPHOS) subunit expression, coupled with increased oxidative stress. Among these, mitochondrial dysfunction is linked to cancer progression through increased ROS production, impaired mitochondrial respiration, ER stress, and alteration of nutrient metabolism.
Phenobarbital accumulation in liver is a subtype of compound accumulation in liver: A process that keeps phenobarbital in the liver. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
phenobarbital accumulation in liver [Ground glass appearance]
Constitutive androstane receptor activation is a subtype of activating nuclear receptor: A process that changes the activity of the activating CAR ( constitutive androstane receptor) with a nuclear receptor role to be higher. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
activating constitutive androstane receptor [Ground glass appearance]
By activating CAR, CAR migrates from the cytoplasm to the nucleus and transcribes the drug metabolizing enzyme Cyp.
constitutive androstane receptor activation [Ground glass appearance]
CAR can induce CYP2B6 and CYP3A4 by activation of the CYP3A4 ER6 (in human).
Phosphorylated Nuclear Receptor CAR Forms a Homodimer To Repress Its Constitutive Activity for Ligand Activation.
Retinoid X receptor activation is a subtype of activating nuclear receptor: A process that changes the activity of the RXR (retinoid X receptor) with a nuclear receptor role to be higher. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
activating retinoid X receptor [Ground glass degeneration]
retinoid X receptor activation [Ground glass appearance]
Hyperfunction of cytochrome p450 gene expression is a subtype of hyperfunction of drug metabolizing enzyme gene expression: A process that performs an excesssive gene expression of cytochrome p450. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
hyperfunction of cytochrome p450 gene expression [Ground glass appearance]
Hyperfunction of drug metabolism phase I is a subtype of hyperfunctioning of drug metabolism: A process that performs an excessive drug metabolism phase I. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
hyperfunction of drug metabolism phase I [Ground glass appearance]
Hyperfunction of iron supply is a subtype of hyperfunctioning: A process that performs an excesssive iorn supply. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
hyperfunction of iron supply [Ground glass appearance]
Hypofunction of decomposing is a subtype of hypofunctioning: A process that performs a decreased or insufficient decomposing.
Hyperfunction of electron transport from NADH to cytochrome P450 is a subtype of hyperfunction of transport: A process that performs an excesssive electron transport from NADH to cytochrome P450. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
hyperfunction of electron transport from NADH to cytochrome P450 [Ground glass appearance]
Forming a complex with Cytochrome P450 is a subtype of protein complex assembly: The aggregation, arrangement and bonding together with Cyp (cytochrome P450) to form a complex. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
forming a complex with Cytochrome P450 [Ground glass appearance]
Hyperfunction of drug metabolism phase II is a subtype of hyperfunction of drug metabolism: A process that performs an excessive drug metabolism phase II. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
hyperfunction of drug metabolism phase II [Ground glass appearance]
The protein encoded by this gene belongs to the ser/thr protein kinase family. It is the catalytic subunit of the 5'-prime-AMP-activated protein kinase (AMPK). AMPK is a cellular energy sensor conserved in all eukaryotic cells. The kinase activity of AMPK is activated by the stimuli that increase the cellular AMP/ATP ratio. AMPK regulates the activities of a number of key metabolic enzymes through phosphorylation. It protects cells from stresses that cause ATP depletion by switching off ATP-consuming biosynthetic pathways. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]
AMPK (canonical)[Ground glass appearance]
Negative regulation of ATP consuming is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of ATP consuming. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
negative regulation of ATP consuming [Ground glass appearance]
Changing balance of phospholipid metabolism is a subtype of changing balance: A process that changes the balance between phospholipid anabolism and catabolism. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
changing balance of phospholipid metabolism [Phospholipidosis]
Increasing demand for response to oxidative stress is a subtype of increasing the demand for response to stress: A process that changes the functional demand for the response to the oxidative stress to be higher. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
increasing demand for response to oxidative stress [Ground glass appearance]
The chemical reaction resulting in the formation of reactive oxygen species, any molecules or ions formed by the incomplete one-electron reduction of oxygen. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
reactive oxygen species biosynthetic process [Ground glass appearance]
This process is totality of all processes through which the phospholipidosis is realized caused by obesity. The severity is moderate.
Overeating is a subtype of increasing quantity: A process that changes the ingestion amount of food to be larger. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
Changing phospholipid homeostasis is a subtype of changing balance: A process that changes the steady state of phospholipid within an organism or cell. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
changing phospholipid homeostasis [Phospholipidosis]
Drug-, radiation-induced, or spontaneous injuries to DNA that introduce deviations from its normal double-helical conformation. These changes include structural distortions that interfere with replication and transcription, as well as point mutations that disrupt base pairs and exert damaging effects on future generations through changes in DNA sequence. If the damage is minor, it can often be repaired (DNA repair); extensive damage can induce apoptosis. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
UGT1A1 (canonical)[Ground glass appearance]
UGT1A1 is inducible by CAR activators such as Phenobarbital.
Any process that modulates the rate or extent of progression through the cell cycle. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
regulation of cell cycle [Ground glass appearance]
Negative regulation of cell junction assembly is a subtype of negative regulation process: Any process that stops, prevents or reduces the frequency, rate or extent of cell junction assembly. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
negative regulation of cell junction assembly [Ground glass appearance]
Expcretion of drug metabolite from hepatocyte to bile tube is a subtype of excretion of compound: A process that excretes the drug metabolite from the hepatocyte to to the bile tube. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
expcretion of drug metabolite from hepatocyte to bile tube [Ground glass appearance]
Changing phospholipid homeostasis is a subtype of changing balance: A process that changes the steady state of phospholipid within an organism or cell.
The chemical reactions and pathways resulting in the breakdown of glycogen, a polydisperse, highly branched glucan composed of chains of D-glucose residues. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
glycogen catabolic process [Ground glass appearance]
Activation of the constitutive androstane receptor inhibits gluconeogenesis without affecting lipogenesis or fatty acid synthesis in human hepatocytes. Activation of mouse constitutive androstane receptor (mCAR) alleviates type 2 diabetes and obesity by inhibiting hepatic gluconeogenesis, lipogenesis, and fatty acid synthesis. However, the role of human (h) CAR in energy metabolism is largely unknown. In this study, activation of hCAR by UM104 and UM145 significantly repressed the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, two pivotal gluconeogenic enzymes, while exerting negligible effects on the expression of genes associated with lipogenesis and fatty acid synthesis. Functional experiments show that UM104 and UM145 markedly inhibit hepatic synthesis of glucose but not triglycerides in human primary hepatocytes (HPH). In contrast, activation of mCAR repressed the expression of genes associated with gluconeogenesis, lipogenesis, and fatty acid synthesis in mouse primary hepatocytes. Therefore, human CAR selectively inhibits gluconeogenesis without suppressing fatty acid synthesis.
Decreasing negative regulator of G1/S transition is a subtype of decreasing quantity: A process that chanes the quantity of the object with a negative regulator of G1/S role to be lower. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
decreasing negative regulator of G1/S transition [Ground glass appearance]
Carbohydrate storage is a subtype of accumulation of substances in a biological object: The accumulation and maintenance in cells or tissues of carbohydrates, any of a group of organic compounds based of the general formula Cx(H2O)y.
The multiplication or reproduction of cells, resulting in the rapid expansion of a cell population. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
cell proliferation [Ground glass appearance]
In transgenic mice, it has been shown that activation of beta-catenin in more than 70% of all hepatocytes causes immediate proliferation leading to hepatomegaly PMID:21822615
Any DNA replication initiation that is involved in cell cycle DNA replication. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
cell cycle DNA replication initiation [Ground glass appearance]
Long-term treatment with CAR activators such as TCPOBOP and Phenobarbital results in a strain- and species-specific induction of liver tumors in rats and micce, which is due to the stimulation of S-phase DNA synthesis leading to hepatocyte proliferation and a decrease in apoptosis.
Smooth endoplasmic reticulum proliferation in hepatocyte is a subtype of endoplasmic reticulum proliferation in hepatocyte: A process that becomes larger in the number of smooth endoplasmic reticulum in hepatocyte(s). This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
increasing number of sER [Ground glass appearance]
smooth endoplasmic reticulum proliferation in hepatocyte [Ground glass appearance]
Any process that stops, prevents or reduces the frequency, rate or extent of signal transduction by p53 class mediator. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
negative regulation of signal transduction by p53 class mediator [Ground glass appearance]
Mechanistically, GADD45B (Yamamoto et al., 2010), an antiapoptotic factor, as well as Mdm2 (Huang et al., 2005), a negative regulator of the p53 tumor suppressor, have been implicated as pathways activated by CAR and contributory to the enhanced tumorigenic response in CAR wild-type animals.
Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
negative regulation of apoptotic process [Ground glass appearance]
Phenobarbital promotes clonal expansion of preneoplastic cells and inhibits apoptosis in rodents. Casarett & Doull's Toxicology: The Basic Science of Poisons, Eighth Edition
PB produced the following changes: (a) accelerated appearance of neoplastic nodules and hepatocellular carcinoma (from 28 weeks onwards); (b) phenotypic changes in altered foci such as a shift from clear to eosinophilic appearance, enhanced expression of gamma-glutamyltranspeptidase and other markers, and more distinct borders from surrounding liver; (c) an increase in foci number; and (d) accelerated foci enlargement.
CAR forms a complex with a growth arrest and DNA damage-inducible beta GADD45B to repress c-Jun N-terminal kinase JNK1 signaling in mouse primary hepatocytes, attenuating apoptosis.
Phenobarbital accumulation in liver is a subtype of compound accumulation in liver: A process that keeps phenobarbital in the liver. This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (sustained) .
phenobarbital accumulation in liver (sustained) [Ground glass appearance]
Constitutive androstane receptor activation by phenobarbital is a subtype of activating nuclear receptor: A process that changes the activity of the activating CAR ( constitutive androstane receptor) with a nuclear receptor role to be higher by phenobarbital. This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (sustained) .
CAR activating [sustained] [Ground glass appearance ]
continued CAR activation [Ground glass appearance]
constitutive androstane receptor activation by phenobarbital (sustained) [Ground glass appearance]
Making existence of foreign substance is a subtype of making existence: A process that puts froreign substances with an object.
Increasing hepatocellular volume is a changing process to change the volume of the hepatocyte to increase. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
increasing hepatocellular volume [Ground glass appearance]
A process that results in an increase in hepatic cell number by cell division, often leading to an increase in the size of an liver. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
hepatocyte proliferation [Ground glass appearance]
Phenotype of single hepatocytes expressing an activated version of β-catenin in liver of transgenic mice.
Increasing hepatic vascular lumen area is a subtype of increasing area: A process that changes the area of the hepatic vascular lumen area to be larger. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
increasing hepatic vascular lumen area [Ground glass appearance]
Increasing liver weight is a subtype of increasing weight: A process that changes the weight of the liver to be higher. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
increasing liver weight [Ground glass appearance]
Increasing volume of liver is a subtype of increasing volume: A process that changes the volume of the liver to be higher. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
increasing volume of liver [Ground glass appearance]
N-(4-oxocyclohexa-2,5-dien-1-ylidene)acetamide [Glutathione depletion]
N-acetyl-1,4-benzoquinone imine [Glutathione depletion]
GADD45B (canonical)[Ground glass appearance]
phenobarbital - apotosis inhibitor [Ground glass appearance]
Glucose homeostasis imbalance is a subtype of chemical homeostasis imbalance: A process that becomes lacking a glucose homeostastasis balance. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
glucose homeostasis imbalance [Ground glass appearance]
reduced oxygenation of body tissues resulting in the decreased pressure of this component of body gases; commonly due to hypoxemia This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
PXR can maximally induce both CYP2B6 and CYP3a4, whereas CAR can maximally induce CYP2B6 and induce CYP3A4 submaximaly due to its weaker binding and functional activation of CYP3A4ER6.
CAR binding is a subtype of binding: Interacting with CAR (constitutive androstane receptor) . This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
Any process that increases the frequency, rate or extent of the passage or uptake of molecules by the mitochondrial membrane. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
positive regulation of mitochondrial membrane permeability [Ground glass appearance]
Decreasing mitochondrial membrane potential is a subtype of decreasing membrane potential: A process that changes the electrical potential of a mitochondrial membrane to be lower. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
decreasing mitochondrial membrane potential [Ground glass appearance]
Negative regulation of cell proliferation inhibitor expression is a subtype of negative regulation of gene expression: A process that stops, prevents, or reduces the frequency, rate or extent of cell proliferation inhibitor expression. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
negative regulation of cell proliferation inhibitor expression [Ground glass appearance]
Ground glass appearance dependent chemical entity is a subtype of toxic course dependent chemical entity. This entity can participate in the course of ground glass appearance.
ground glass appearance dependent chemical entity
Ground glass appearance dependent molecule is a subtype of toxic course dependent chemical entity. This molecule can participate in the course of ground glass appearance as a gene product. Gene profile:Rat/Liver/
ground glass appearance dependent molecule (rat invivo)
Catenin Beta 1 [Ground glass appearance]
Activating CAR and beta-catenin induces uncontrolled liver growth and tumorigenesis.
Dioxins and dioxin-like compounds accumulation in liver is a subtype of compound accumulation in liver: A process that keeps dioxins and dioxin-like compoundsin the liver. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
dioxins and dioxin-like compounds accumulation in liver [Ground glass appearance]
Aryl hydrocarbon receptor activation is a subtype of activating nuclear receptor: A process that changes the activity of the activating AhR (aryl hydrocarbon receptor) with a nuclear receptor role to be higher. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
AhR activity is combining with an aryl hydrocarbon and transmitting the signal to initiate a change in cell activity. The aryl hydrocarbon receptor is a ligand-activated transcription factor which translocates to the nucleus to activate transcription upon ligand-binding.Combining with an aryl hydrocarbon and transmitting the signal to initiate a change in cell activity. The aryl hydrocarbon receptor is a ligand-activated transcription factor which translocates to the nucleus to activate transcription upon ligand-binding.
activating aryl hydrocarbon receptor [Ground glass appearance]
aryl hydrocarbon receptor activation [Ground glass appearance]
AhR with ARNT to induce CYP1A1, 1B1, and 2S1. ≈
AHR (canonical)[Ground glass appearance]
Transcription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress. Binds to the insulin response element (IRE) with consensus sequence 5-TT[G/A]TTTTG-3 and the related Daf-16 family binding element (DBE) with consensus sequence 5-TT[G/A]TTTAC-3. Activity suppressed by insulin. Main regulator of redox balance and osteoblast numbers and controls bone mass. Orchestrates the endocrine function of the skeleton in regulating glucose metabolism. Acts synergistically with ATF4 to suppress osteocalcin/BGLAP activity, increasing glucose levels and triggering glucose intolerance and insulin insensitivity. Also suppresses the transcriptional activity of RUNX2, an upstream activator of osteocalcin/BGLAP. In hepatocytes, promotes gluconeogenesis by acting together with PPARGC1A and CEBPA to activate the expression of genes such as IGFBP1, G6PC and PCK1. Important regulator of cell death acting downstream of CDK1, PKB/AKT1 and STK4/MST1. Promotes neural cell death. Mediates insulin action on adipose tissue. Regulates the expression of adipogenic genes such as PPARG during preadipocyte differentiation and, adipocyte size and adipose tissue-specific gene expression in response to excessive calorie intake. Regulates the transcriptional activity of GADD45A and repair of nitric oxide-damaged DNA in beta-cells. Required for the autophagic cell death induction in response to starvation or oxidative stress in a transcription-independent manner. Mediates the function of MLIP in cardiomyocytes hypertrophy and cardiac remodeling (By similarity).
insulin receptor signaling pathway is a subtype of integrated signaling pathway: The series of molecular signals generated as a consequence of the insulin receptor binding to insulin. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
insulin receptor signaling pathway [ER stress]
TGF (canonical)[Ground glass appearance]
Swelling-induced Src regulates cytoskeletal dynamics, through Vav, and fluid efflux, through PLCgamma, and thus can coordinate structural reorganization with fluid balance to maintain cellular integrity. Vav mediates cytoskeletal reorganization as a consequence of its activation of Rho GTPases at different times and places within the cell, whereas PLCγ mediates the activation of volume-sensitive K+ and Cl– channels and osmotically driven fluid efflux. Together, these effectors regulate cell volume recovery.
MDM2 (canonical)[Ground glass appearance]
PPARalpha activation is a subtype of activating nuclear receptor: A process that changes the activity of the activating PPAR alpha (Peroxisome Proliferator Activated Receptor Alpha) with a nuclear receptor role to be higher. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
PPARalpha activation [Eosinophilic granular degeneration]
A cell aging process stimulated in response to cellular stress, whereby normal cells lose the ability to divide through irreversible cell cycle arrest. This process can constitute the course of Ground glass appearance.
cellular senescence [Ground glass appearance]
Ground glass appearance dependent molecule is a subtype of toxic course dependent chemical entity. This molecule can participate in the course of ground glass appearance as a gene product. Gene profile:Human/in vitro/Hepatocyte/
ground glass appearance dependent gene (human in vitro)
PPARalpha activation is a subtype of activating nuclear receptor: A process that changes the activity of the activating PPAR alpha (Peroxisome Proliferator Activated Receptor Alpha) with a nuclear receptor role to be higher. The degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
PPARalpha activation (moderate) [Eosinophilic granular degeneration]
Hypofunction of carbohydrate transport is a subtype of hypofunction of transport: A process that performs a decreased or insufficient carbohydrate transport. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
hypofunction of carbohydrate transport [Ground glass appearance]
PPARalpha activation is a subtype of activating nuclear receptor: A process that changes the activity of the activating PPAR alpha (Peroxisome Proliferator Activated Receptor Alpha) with a nuclear receptor role to be higher. The degree is mild. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
PPARalpha activation (mild) [Eosinophilic granular degeneration]
A pathologic process that involves the transformation of normal cells to a neoplastic state and resulting in polyclonal or monoclonal neoplastic cell proliferation. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
Phenobarbital does not increase the liver tumors in humans.
CAR is the molecular target of promotion by PB and that activation of this receptor is an essential requirement for liver tumor development in mice.
RNA splicing is a subtype of removing: The process of removing sections of the primary RNA transcript to remove sequences not present in the mature form of the RNA and joining the remaining sections to form the mature form of the RNA. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
Peroxisomal proliferation in hepatocyte is a subtype of hepatocyte organelle proliferation: A process that becomes larger in the number of peroxisome in hepatocyte(s). The degree is mild. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
peroxisomal proliferation in hepatocyte (mild) [Eosinophilic granular degeneration]
Any process that stops, prevents, or reduces the frequency, rate or extent of autophagy. Autophagy is the process in which cells digest parts of their own cytoplasm. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
negative regulation of autophagy [Ground glass appearance]
DDB2 (canonical)[Ground glass appearance]
Influence of aryl hydrocarbon- (Ah) receptor and genotoxins on DNA repair gene expression and cell survival of mouse hepatoma cells: As two NER genes, XP-C and DNA damage binding protein ddb2, are up-regulated by p53 and ultraviolet radiation in human cells these findings suggest cell type, species or lesion specific actions of p53 on DNA repair gene expression.
In this study, generation of hepatocyte-specific Ddx3x-knockout mice revealed that loss of Ddx3x facilitates liver tumorigenesis. Loss of Ddx3x led to profound ductular reactions, cell apoptosis, and compensatory proliferation in female mutants at 6 weeks of age.
Modulator recognition factor 1, an AT-rich interaction domain family member, is a novel corepressor for estrogen receptor alpha.
Regulation of inflammatory responses by dynamic subcellular localization of RNA-binding protein Arid5a.
An enzyme that catalyzes L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate
Peroxisomal proliferation in hepatocyte is a subtype of hepatocyte organelle proliferation: A process that becomes larger in the number of peroxisome in hepatocyte(s). The degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
peroxisomal proliferation in hepatocyte (moderate) [Eosinophilic granular degeneration]
Peroxisomal proliferation in hepatocyte is a subtype of hepatocyte organelle proliferation: A process that becomes larger in the number of peroxisome in hepatocyte(s). The degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
peroxisomal proliferation in hepatocyte (severe) [Eosinophilic granular degeneration]
A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
apoptotic process [Ground glass appearance]
An enzyme that catalyzes L-alanine + 2-oxoglutarate = pyruvate + L-glutamate
Tumor growth is a subtype of cell growth: The process in which a tumor cell increases in size. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
MYC promotes cell growth and proliferation, and alters cellular metabolism to enhance the provision of precursors for phospholipids and cellular macromolecules. Here we show in human and murine cell lines that oncogenic levels of MYC establish a dependence on AMPK-related kinase 5 (ARK5; also known as NUAK1) for maintaining metabolic homeostasis and for cell survival. ARK5 is an upstream regulator of AMPK and limits protein synthesis via inhibition of the mammalian target of rapamycin 1 (mTORC1) signalling pathway. ARK5 also maintains expression of mitochondrial respiratory chain complexes and respiratory capacity, which is required for efficient glutamine metabolism. Inhibition of ARK5 leads to a collapse of cellular ATP levels in cells expressing deregulated MYC, inducing multiple pro-apoptotic responses as a secondary consequence. Depletion of ARK5 prolongs survival in MYC-driven mouse models of hepatocellular carcinoma, demonstrating that targeting cellular energy homeostasis is a valid therapeutic strategy to eliminate tumour cells that express deregulated MYC.
Myc has been shown to establish a dependence on AMPK-related ARK5 to maintain metabolic homeostasis and cell survical. Depletion of ARK5 prolongs cell survival in MYC-driven mouse model of hepatocellular carcinoma, suggensting that targeting cellular energy homeostasis is a valid therapeutic strategy to eliminate tumor cells that express deregulate myc.
Increasing demand for response to mitochondrial oxidative stress is a subtype of increasing the demand for response to oxidative stress: A process that changes the functional demand for the response to the mitochondrial oxidative stress to be higher. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
increasing demand for response to mitochondrial oxidative stress [Mitochondrial disorder]
Furthermore, enhanced mtFAO without concomitant up‐regulation of the mitochondrial respiratory chain (MRC) activity induces reactive oxygen species (ROS) overproduction within different MRC components upstream of cytochrome c oxidase. This event seems to play a significant role in the initiation of oxidative stress and subsequent development of nonalcoholic steatohepatitis (NASH) in some individuals. Furthermore, high glucose levels promote ROS overproduction within hepatocytes, thus favoring oxidative stress and mitochondrial dysfunction.
Metabolic reprogramming by PCK1 promotes TCA cataplerosis, oxidative stress and apoptosis in liver cancer cells and suppresses hepatocellular carcinoma.
Tumor cell proliferation is a subtype of cell proliferation: A process of the multiplication or reproduction of tumor cells, resulting in the rapid expansion of a tumor cell population. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
tumor cell proliferation [Ground glass appearance]
PB produced the following changes: (a) accelerated appearance of neoplastic nodules and hepatocellular carcinoma (from 28 weeks onwards)
Increasing number of dead cells in liver is a subtype of cell proliferation: A process that becomes larger in the number of dead cells in the liver. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
increasing number of dead cells in liver [Ground glass appearance]
The spread or migration of cancer cells from one part of the body (the organ in which it first appeared) to another. The secondary tumor contains cells that are like those in the original (primary) tumor. [def-source: NCI] This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
Lack of adherens juctions contributes to the invasiveness of tumor cells.
Eosinogranular degeneration dependent molecule is a subtype of toxic course dependent chemical entity. This gene can participate in the course of eosinogranular degeneration as a gene product. Gene profile:Human/in vitro/Hepatocyte/
eosinogranular degeneration dependent molecule (human in vitro)
Modulator recognition factor 1, an AT-rich interaction domain family member, is a novel corepressor for estrogen receptor alpha: As with full-length ERα, MRF1 interacted in a ligand-dependent manner with thyroid receptor α (TRα) and the retinoid X receptor α (RXRα). MRF1 bound to ERβ, the androgen receptor (AR), and the retinoic acid receptor (RAR) in a ligand-independent manner in these assays. MRF1 was able to repress several other members of the nuclear hormone receptor family.
Differentially regulated gene expression in quiescence versus senescence and identification of ARID5A as a quiescence associated marker:The endogenous expression of ARID5A increased during serum starved condition of quiescence. Overexpression of ARID5A resulted in more number of cells in G0/G1 phase of cell cycle.
Hypofunction of fatty acid degradation is a subtype of hypofunctioning: A process that performs a decreased or insufficient lipid degradation. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
hypofunction of fatty acid degradation [Lipidosis]
PTPN4 (human)[Eosinophilic granular degeneration]
PTPH1 was expressed in HCCs and hepatocytes.
Lipid homeostasis imbalance is a subtype of chemical homeostasis imbalance: A process that becomes lacking a lipid homeostastasis balance. This entity is a specific course-dependent process. The degree is severe. This process can constitute the course of Lipidosis.
lipid homeostasis imbalance (severe) [Lipidosis]
Lipid metabolism imbalance is a subtype of imbalance: A process that becomes lacking a homeostastasis balance of lipid metabolism. The degree is mild. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
lipid metabolism imbalance (mild) [Lipidosis]
Lipid metabolism imbalance is a subtype of imbalance: A process that becomes lacking a homeostastasis balance of lipid metabolism. The degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
lipid metabolism imbalance (moderate) [Lipidosis]
The totality of all processes through which alcoholic fatty liver is realized.
Lipid accumulation in hepatocyte (severe) is a subtype of lipid strorage in hepatocyte: A process that keeps lipids in hepatocytes. And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
lipid storage in hepatocyte (moderate) [Lipidosis]
lipid accumulation in hepatocyte (moderate) [Lipidosis]
Lipid homeostasis imbalance is a subtype of chemical homeostasis imbalance: A process that becomes lacking a lipid homeostastasis balance. The degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
lipid homeostasis imbalance (moderate) [Lipidosis]
Lipid metabolism imbalance is a subtype of imbalance: A process that becomes lacking a homeostastasis balance of lipid metabolism. The degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
lipid metabolism imbalance (severe) [Lipidosis]
Pex11a (mouse)[Eosinophilic granular degeneration]
PEX11alpha is required for peroxisome proliferation in response to 4-phenylbutyrate but is dispensable for peroxisome proliferator-activated receptor alpha-mediated peroxisome proliferation.
PEX11alpha gene is activated by PPARalpha in the liver
PEX11 family members are membrane elongation factors that coordinate peroxisome proliferation and maintenance.
ACOT4 (human)[Eosinophilic granular degeneration]
Repeated restraint stress up-regulated Pparα and its target genes in the liver, including Acox, Acot1, Acot4, Cyp4a10, Cyp4a14 and Lipin2, an effect that was highly correlated with Hnf4α
The birth rate of Elovl6 knockout mice was lower, and the surviving mice were smaller in size and had reduced body weight. Crucial role of a long-chain fatty acid elongase, Elovl6, in obesity-induced insulin resistance. Secondary regulation of PPARa activity could be a part of SREBP-1c/Elovl6 regulation of lipogenesis.
Elovl6 (rat)[Eosinophilic granular degeneration]
Hsdl2 (rat)[Eosinophilic granular degeneration]
Moving free fatty acid to the hepatocyte is a subtype of moving A to the inside of B: A process of the movement of free fatty acid into a hepatocyte. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
moving fatty acid to the hepatocyte [lipidosis]
CPT1 (canonical)[Eosinophilic granular degeneration]
Mgll (rat)[Eosinophilic granular degeneration]
Any process that stops, prevents or reduces the frequency, rate or extent of cellular senescence. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
negative regulation of cellular senescence [Ground glass appearance]
Cyp4a3 (rat)[Eosinophilic granular degeneration]
Catalysis role of the reaction: ATP + protein L-tyrosine = ADP + protein L-tyrosine phosphate by a non-membrane spanning protein.
non-membrane spanning protein tyrosine kinase
Plin2 (mouse)[Eosinophilic granular degeneration]
Lipid droplets (LDs) undergo hydrolysis (lipolysis) to generate free fatty acids for energetic purposes. LD-associated proteins perilipin 2 (PLIN2) and perilipin 3 (PLIN3) are CMA substrates and their degradation through CMA precedes lipolysis. In vivo studies revealed that Chaperone-mediated autophagy (CMA) degradation of PLIN2 and PLIN3 was enhanced during starvation, concurrent with elevated levels of cytosolic adipose triglyceride lipase (ATGL) and macroautophagy proteins on LDs.
Decreasing lipid is a subtype of decreasing quantity: A process that changes the quantity of the lipid to be lower. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis (normal condition).
ACOT3 is involved in the transport of DCAdicarboxylic acids into the peroxisomes by hydrolysis of long-medium chain fatty acyl-CoA esters to FFA, which can be further transported out of peroxisomes to mitochondria for beta-oxidation or excreted in the urinPMID:23359794 At the gene level, this was reflected by the up-regulation of cytochrome P450 (Cyp) 4a10, Cyp4a14, Cyp4a31 and Acyl-CoA thioesterase 3 (Acot3). Two relevant regulators, cytochrome P450 oxidoreductase (Por, rate limiting for cytochrome P450s) and the transcription factor constitutive androstane receptor (Car; official symbol Nr1i3) were also up-regulated in the quercetin-fed mice.
Acot3 (mouse)[Eosinophilic granular degeneration]
Acot2 (mouse)[Eosinophilic granular degeneration]
cytosolic ACOT1 becomes downregulated as the cellular use of acyl-CoA increases, while mitochondrial ACOT2 is upregulated as the beta-oxidation capacity increases. ACOT isoform expression may be regulated during brown adipocyte differentiation to support the fat storage and combustion characteristics of this cell type.
Acyl-CoA thioesterase-2 facilitates mitochondrial fatty acid oxidation in the liver.
Increasing lipid is a subtype of increasing quantity: A process that changes the amount of lipid to be larger. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
Acox1 (rat)[Eosinophilic granular degeneration]
PPAR agonists induced the peroxisomal enzymes, acyl-coenzyme A (CoA) oxidase (Acox), enoyl-CoA hydratase/L-3-hydroxyacyl-CoA dehydrogenase (Ehhadh), and 3-ketoacyl-CoA thiolase (Acaa1) at the transcriptional level in rat hepatocytes, but not dog hepatocytes
Ehhadh (rat)[Eosinophilic granular degeneration]
Increasing lipid is a subtype of increasing quantity: A process that changes the amount of lipid to be larger.
IL-1beta processing is a subtype of protein processing: A process that IL-1beta maturation process achieved by the cleavage of pro IL-1beta.
Cpt2 (rat)[Eosinophilic granular degeneration]
IL-1beta processing is a subtype of protein processing: A process that IL-1beta maturation process achieved by the cleavage of pro IL-1beta. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
Slc25a20 (rat)[Eosinophilic granular degeneration]
Acot12 (rat)[Eosinophilic granular degeneration]
Acot7 (rat)[Eosinophilic granular degeneration]
Acot7 mRNA levels are increased in human islets in type 2 diabetes,
ACOT8 (human)[Eosinophilic granular degeneration]
Hadhb (rat)[Eosinophilic granular degeneration]
Ground glass appearance dependent molecule is a subtype of toxic course dependent chemical entity. This molecule can participate in the course of ground glass appearance as a gene product. Gene profile:Mouse/Liver/
ground glass appearance dependent molecule (mouse)
Ctnnb1 -tumor positive regulator (mouse)[Ground glass appearance]
Ctnnb1 -apoptosis inhibitor (mouse)[Ground glass appearance]
Acaa1a (rat)[Eosinophilic granular degeneration]
Increasing lipid material is a subtype of increasing quantity: A process that changes the amount of lipid material to be larger.
Ctnnb1 -cell senescence inhibitor (mouse)[Ground glass appearance]
Eosinogranular degeneration dependent molecule is a subtype of toxic course dependent chemical entity. This gene can participate in the course of eosinogranular degeneration as a gene product. Gene profile:Rat/Liver/
eosinogranular degeneration dependent molecule (rat)
Increasing lipid material is a subtype of increasing quantity: A process that changes the amount of lipid material to be larger. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis (normal condition).
CASP1 -IL1beta activator (canonical)[lipidosis]
A role played by the entity that activates the activity of the cytokine IL-1b.
Cyp4a1 (rat)[Eosinophilic granular degeneration]
A role played by the entity which regulates the cellular senescence.
Any process that increases the frequency, rate or extent of the passage or uptake of molecules by the mitochondrial membrane. This entity is a specific course-dependent process. This process can constitute the course of lipidosis.
positive regulation of mitochondrial membrane permeability [lipidosis]
PLIN2 (human)[Eosinophilic granular degeneration]
PPARalpha activators and fasting induce the expression of adipose differentiation-related protein in liver. ADFP is transcriptionally regulated by peroxisome proliferator-activated receptor alpha (PPARalpha) in mouse liver and rat and human hepatoma cells through a highly conserved direct repeat-1(DR-1) element
An intimate collaboration between peroxisomes and lipid bodies. The extensive physical contact between peroxisomes and lipid bodies promotes the coupling of lipolysis within lipid bodies with peroxisomal fatty acid oxidation.
Decreasing mitochondrial membrane potential is a subtype of decreasing membrane potential: A process that changes the electrical potential of a mitochondrial membrane to be lower. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
decreasing mitochondrial membrane potential [lipidosis]
The chemical reaction resulting in the formation of reactive oxygen species, any molecules or ions formed by the incomplete one-electron reduction of oxygen. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
reactive oxygen species biosynthetic process [lipidosis]
A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
Lipidosis dependent molecule is a subtype of toxic course dependent chemical entity. This molecule can participate in the course of lipidosis as a gene product. Gene profile:Rat/Liver/
Lipidosis dependent chemical entity is a subtype of toxic course dependent chemical entity. This entity can participate in the course of lipidosis.
Lipidosis dependent molecule is a subtype of toxic course dependent chemical entity. This molecule can participate in the course of lipidosis as a gene product. Gene profile:Human/in vitro/Hepatocyte/
lipidosis dependent molecule (human in vitro)
This gene encodes the mitochondrial enzyme which is catalyzes the rate-limiting step in heme (iron-protoporphyrin) biosynthesis.
The protein levels of ADH1A, ADH1B, and ADH4 were each decreased in the NASH groups, which was consistent with a decreased overall ADH activity. The protein level of ALDH2 was significantly increased in both NASH groups, while ALDH1A1 and ALDH1B1 were only decreased in NASH (fatty) samples. ALDH activity represented by oxidation of acetaldehyde was decreased in the NASH (fatty) group.
Hypofunction of alcohol metabolism is a subtype of hyperfunctioning: A process that performs a decreased or insufficient alcohol metabolism. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
hyporfunction of alcohol metabolism [Lipidosis]
The protein levels of ADH1A, ADH1B, and ADH4 were each decreased in the NASH groups, which was consistent with a decreased overall ADH activity.
Hypofunction of alcohol metabolism is a subtype of hyperfunctioning: A process that performs a decreased or insufficient alcohol metabolism.
Mechanisms of the Anti-Obesity Effects of Oxytocin in Diet-Induced Obese Rats With regard to its mechanism of action in adipose tissue, oxytocin increased the expression of stearoyl-coenzyme A desaturase 1, as well as the tissue content of the phospholipid precursor, N-oleoyl-phosphatidylethanolamine, the biosynthetic precursor of the oleic acid-derived PPAR-alpha activator, oleoylethanolamide.
Hypooxytocinaemia in obese Zucker rats relates to oxytocin degradation in liver and adipose tissue. OXTR mRNA and protein levels were upregulated in the adipose tissue of obese animals in contrast to the reduced OXTR protein levels in skeletal muscle. Our results show that obesity is associated with reduced plasma oxytocin due to increased peptide degradation by liver and adipose tissue rather than changes in hormone synthesis.
A fatty acid oxidation process that results in the complete oxidation of a long-chain fatty acid. Fatty acid beta-oxidation begins with the addition of coenzyme A to a fatty acid, and occurs by successive cycles of reactions during each of which the fatty acid is shortened by a two-carbon fragment removed as acetyl coenzyme A; the cycle continues until only two or three carbons remain (as acetyl-CoA or propionyl-CoA respectively). This entity is a specific course-dependent process. This process can constitute the course of lipidosis in the adipose tissuees.
fatty acid beta-oxidation in adipose tissue [lipidosis]
With regard to its mechanism of action in adipose tissue, oxytocin increased the expression of stearoyl-coenzyme A desaturase 1, as well as the tissue content of the phospholipid precursor, N-oleoyl-phosphatidylethanolamine, the biosynthetic precursor of the oleic acid-derived PPAR-alpha activator, oleoylethanolamide. Because PPAR-alpha regulates fatty acid β-oxidation, we hypothesized that this transcription factor might mediate the oxytocin effects.
Increasing free fatty acid is a subtype of increasing quantity: A process that changes the amount of free fatty acid to be larger.
NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice
New mitochondrial DNA synthesis enables NLRP3 inflammasome activation: Toll-like receptors signal via the MyD88 and TRIF adaptors to trigger IRF1-dependent transcription of CMPK2, a rate-limiting enzyme that supplies deoxyribonucleotides for mtDNA synthesis. CMPK2-dependent mtDNA synthesis is necessary for the production of oxidized mtDNA fragments after exposure to NLRP3 activators. Cytosolic oxidized mtDNA associates with the NLRP3 inflammasome complex and is required for its activation.
Lipidosis dependent molecule is a subtype of toxic course dependent chemical entity. This molecule can participate in the course of lipidosis as a gene product. Gene profile:Mouse/Liver/
Inflammasome activation is a subtype of activating: A process that changes the activity of the inflammasome to be higher.
Upstream stimulatory factors bind to insulin response sequence of the fatty acid synthase promoter. USF1 is regulated.
Upstream stimulatory factor binding to the E-box at -65 is required for insulin regulation of the fatty acid synthase promoter.
Essential role in vivo of upstream stimulatory factors for a normal dietary response of the fatty acid synthase gene in the liver.
USF1 activation is a subtype of molecular activation: A process that changes the activity of the USF1 to be higher.
USF1 activation is a subtype of molecular activation: A process that changes the activity of the USF1 to be higher. This entity is a specific course-dependent process. This process can constitute the course of lipidosis.
SREBP activation is a subtype of molecular activation: A process that changes the activity of the SREBP to be higher.
SREBP activation is a subtype of molecular activation: A process that changes the activity of the SREBP to be higher. This entity is a specific course-dependent process. This process can constitute the course of lipidosis.
The decreased expression of hepatic FXR is associated with an increased expression of LXR, SREBP-1C, and hepatic triglyceride synthesis; furthermore, increased SREBP-1C is associated with the degree of hepatic steatosis in the NAFLD patients.
Malfunctioning of insulin signaling is a subtype of malfunctioning process: A process that cannot perform insulin signaling [biological] appropriately or cannot realize it at all. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
malfunctioning of insulin signaling [lipidosis]
Liver X receptor activation is a subtype of activating nuclear receptor: A process that changes the activity of the activating LXR ( liver X receptor) with a nuclear receptor role to be higher. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
Upregulation of SREBP-1c and ChREBP has been speculated to be the principal regulators of NAFLD formation, which is induced by insulin resistance and transcriptionally controlled by LXRa
Increasing NAD/NAD+ ratio is a subtype of increasing ratio: A process that changes the ratio of NAD to NAD+ to be higher. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
ChREBP activation is a subtype of activating nuclear receptor: A process that changes the activity of the activating ChREBP to be higher. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
Carbohydrate-Responsive Element-Binding Protein [lipidosis]
Malfunctioning of insulin signaling is a subtype of malfunctioning process: A process that cannot perform insulin signaling [biological] appropriately or cannot realize it at all.
Dysfunction of peroxisomal fatty acid beta-oxidation is a subtype of hypofunction of fatty acid beta-oxidation: A process that performs a decreased or insufficient fatty acid degradation severely. This entity is a specific course-dependent process. This process can constitute the course of NASH.
dysfunction of peroxisomal fatty acid beta-oxidation [NASH]
The totality of all processes through which non-alcoholic steatohepatitis (NASH) is realized.
non-alcoholic steatohepatitis (toxic course)
The totality of all processes through which simple steatosis is realized.
Lipid accumulation in hepatocyte is a subtype of lipid strorage in hepatocyte: A process that keeps lipids in hepatocytes mildly. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
lipid accumulation in hepatocyte [lipidosis]
lipid strorage in hepatocyte [Lipidosis]
Malfunctioning of TCA cycle is a subtype of malfunctioning of metabolism: A process that cannot perform a tricarboxylic acid cycle appropriately or cannot realize it at all. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
Increasing acetyl CoA is a subtype of increasing quantity: A process that changes the amount of acetyl CoA to be larger. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
Increasing production amount of acetaldehyde is a subtype of increasing quantity: A process that changes the production amount of acetaldehyde to be higher. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
Increasing production amount of acetaldehyde [lipidosis]
Ethanol administration to rodents or ethanol exposure to ethanol-metabolizing cultured cells causes a general down-regulation of PPAR-α. Further, RXR-PPAR-α extracted from hepatoma cells previously exposed to ethanol or acetaldehyde binds poorly to an oligonucleotide containing peroxisome proliferator response elements, indicating that acetaldehyde is responsible for the action of ethanol. It is possible that acetaldehyde, because of its ability to covalently bind proteins]can form adducts with the PPAR-α transcription complex, thereby preventing its ability to bind the promoter element(s).
Phospholipidosis dependent chemical entity is a subtype of toxic course dependent chemical entity. This entity can participate in the course of phospholipidosis.
phospholipidosis dependent chemical entity
Phospholipidosis dependent molecule is a subtype of toxic course dependent chemical entity. This gene can participate in the course of phospholipidosis as a gene product. Gene profile:Rat/Liver/
phospholipidosis dependent molecule (rat)
Phospholipidosis dependent molecule is a subtype of toxic course dependent chemical entity. This gene can participate in the course of Phospholipidosis as a gene product. Gene profile:Human/in vitro/Hepatocyte/
phospholipidosis dependent molecule (human in vitro)
Involvement of choline transporter-like proteins, CTL1 and CTL2, in glucocorticoid-induced acceleration of phosphatidylcholine synthesis via increased choline uptake. Phosphatidylcholine (PC) production is accelerated by glucocorticoid, such as dexamethasone (DEX), which enhances fetal lung maturation, promotes differentiation of alveolar type II (ATII) cells, and increases production of both lipid and protein components of lung surfactant. Choline uptake may play a critical role in PC production and lung surfactant homeostasis for normal breathing. Choline transport in A549 cells is increased by treatment with DEX, and the increase is mediated by induction of functional choline transporters CTL1 and CTL2.
Cho transports from the extracellular space to the cytosol (Homo sapiens)
A conserved inositol phospholipid binding site within the pleckstrin homology domain of the Gab1 docking protein is required for epithelial morphogenesis. (PMID:10531383)
GRB2-associated binding protein 1 [Phospholipidosis]
Phosphoinositide 3-kinases in lysophosphatidic acid signaling: regulation and cross-talk with the Ras/mitogen-activated protein kinase pathway.
Lysophosphatidic acid-induced squamous cell carcinoma cell proliferation and motility involves epidermal growth factor receptor signal transactivation.
Sphingosine 1-phosphate and cancer Nature Reviews Cancer 10, 489-503 (2010)
Recently, whole-exome sequencing analysis on a pedigree with a dominantly inherited immunodeficiency and autoimmunity identified a causal mutation in a gene related to PLB1, the phospholipase Cγ2 (PLCG2) gene.
A role played by the entity which negative regulates the cellular senescence.
Up-regulation of the fibroblast growth factor 8 subfamily in human hepatocellular carcinoma for cell survival and neoangiogenesis. FGF8, FGF17, and FGF18 are involved in autocrine and paracrine signaling in HCC and enhance the survival of tumor cells under stress conditions, malignant behavior, and neoangiogenesis. Thus, the FGF8 subfamily supports the development and progression of hepatocellular malignancy.
FGF18 as a prognostic and therapeutic biomarker in ovarian cancer. (
The chemical reactions and pathways resulting in the formation of lipids, compounds soluble in an organic solvent but not, or sparingly, in an aqueous solvent. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
X-box binding protein 1 (XBP1), known as a key regulator of the unfolded protein response (UPR) secondary to ER stress, is a only recently characterized regulator of hepatic lipogenesis. Regulation of hepatic lipogenesis by the transcription factor XBP1. Science 2008; 320: 1492-1496. XBP1 protein expression in mice was elevated after feeding carbohydrates and corresponded with the induction of critical genes involved in fatty acid synthesis. Inducible, selective deletion of XBP1 in the liver resulted in marked hypocholesterolemia and hypotriglyceridemia, secondary to a decreased production of lipids from the liver. This phenotype was not accompanied by hepatic steatosis or compromise in protein secretory function. The identification of XBP1 as a regulator of lipogenesis has important implications for human dyslipidemias.
Biosynthesis of anandamide and N-palmitoylethanolamine by sequential actions of phospholipase A2 and lysophospholipase D.
Sphingomyelin Regulates the Activity of Secretory Phospholipase A2 in the Plasma Membrane.
IL2->IL2R->PI3K->Akt->Bcl2/c-myc->Cell cycle progression IL2->IL2R->PI3K->Akt->Bcl2->anti-apoptosis
interleukin 2 receptor, beta [Phospholipidosis]
Genes Dev. 1999 Nov 15;13(22):2905-27. Cellular survival: a play in three Akts.
Mol Cell Biol. 2000 Oct;20(19):7109-20. New role for Shc in activation of the phosphatidylinositol 3-kinase/Akt pathway. Experiments with the chimeric receptors indicate that Shc also signals to the PI-3K/Akt pathway in response to IL-2. Our results suggest that cytokine receptors lacking direct PI-3K binding sites activate Akt via a Shc/Grb2/Gab2/PI-3K pathway, thereby regulating cell survival and/or proliferation.
IL-2 receptor signaling through the Shb adapter protein in T and NK cells.
Transduction of interleukin-2 antiapoptotic and proliferative signals via Akt protein kinase.
Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
negative regulation of apoptotic process [Glutathione depletion]
Hyperfunction of alcohol metabolism is a subtype of hyperfunctioning: A process that performs an excessive alcohol metabolism. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
hyperfunction of alcohol metabolism [lipidosis]
Sphingosine-1-phosphate lyase potentiates apoptosis via p53- and p38-dependent pathways and is down-regulated in colon cancer. Proc Natl Acad Sci U S A. 2006;103: 17384–17389.
Subcellular localization and membrane topology of sphingosine-1-phosphate lyase in rat liver.
Increased mRNA Levels of Sphingosine Kinases and S1P Lyase and Reduced Levels of S1P Were Observed in Hepatocellular Carcinoma in Association with Poorer Differentiation and Earlier Recurrence: Inhibition of SPL expression by siRNA led to reduced proliferation and invasion, while overexpression of SPL caused enhanced proliferation of HCC cell lines.
Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of lipids. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
positive regulation of lipid biosynthetic process [lipidosis]
Lipidosis (normal course) is a subtype of process sequences: The courses of processes through which lipid homeostasis balance is keeping.
Lipidosis is a subtype of process sequences: The courses of processes through which lipidosis is realized.
keeping lipid metabolism balance is a subtype of maintaining balance: A process that keeps a balance of lipid metabolism.
maintaining lipid metabolism balance is a subtype of maintaining balance: A process that keeps a balance of lipid metabolism. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
maintaining lipid metabolism balance [Lipidosis]
Gadd45 stress sensors in malignancy and leukemia.
Gadd45 in stress signaling, cell cycle control, and apoptosis. In vivo, Gadd45 proteins can contribute to p38 activation either by activation of upstream kinase(s) or by direct interaction. In addition to being p53-regulated, Gadd45a has been found to contribute to p53 activation via p38.
A family of stress-inducible GADD45-like proteins mediate activation of the stress-responsive MTK1/MEKK4 MAPKKK. Cell 95: 521-530, 1998.
Orthologs of the human CYP2B6 genes can be found in other species including rats, mice, and dogs, which are termed Cyp2b1, Cyp2b10, and CYP2B11, respectively
FEBS Lett. 2002 Feb 13;512(1-3):319-22. Hydroxylation of fatty acids by microsomal and reconstituted cytochrome P450 2B1.
The phenobarbital (PB)-induced up-regulation of CYP2B, CYP2E1 and CYP1A1 isozymes was markedly higher in choline deprivation (CD) than in NF rats. In addition, PB increased glutathione-S-transferase activity only in CD rats. Hepatic glutathione content (GSH) was suppressed by paracetamol (ACET) in normaly fed rats, whereas the drug increased GSH in CD rats. These data suggest that CD has a significant impact on the hepatic metabolic functions, and in particular on those related to drug metabolism.
Effects of Nonalcoholic Fatty Liver Disease on Hepatic CYP2B1 and in Vivo Bupropion Disposition in Rats Fed a High-Fat or Methionine/Choline-Deficient Diet.
Changing balance of lipid metabolism is a subtype of changing balance: A process that changes the balance between lipid anabolism and catabolism. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
changing balance of lipid metabolism [Lipidosis]
Changing balance of lipid metabolism is a subtype of changing balance: A process that changes the balance between lipid anabolism and catabolism.
Changing lipid homeostasis is a subtype of changing balance: A process that changes the steady state of lipid within an organism or cell.
Changing lipid homeostasis is a subtype of changing balance: A process that changes the steady state of lipid within an organism or cell. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
Any process involved in the maintenance of an internal steady state of lipid within an organism or cell.
ATP degradation is a subtype of catabolic process: A process of the chemical reactions resulting in the breakdown of ATP: ATP + H2O = ADP + phosphate + 2 H+.
Cholesteroltransport gene mutation is a subtype of gene mutation: A process thatchanges the sequence of a cholesterol transport gene.
Any process involved in the maintenance of an internal steady state of lipid within an organism or cell. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
maintaining lipid homeostasis [Lipidosis]
Keeping amount of lipid in liver is a subtype of keeping amount: A process that maintaining the amount of lipid in the liver.
Keeping amount of lipid in liver is a subtype of keeping amount: A process that maintaining the amount of lipid in the liver. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis (normal condition).
keeping amount of lipid in liver [Lipidosis]
Overexpression of a mammalian ethanolamine-specific kinase accelerates the CDP-ethanolamine pathway.
Hepatic cytochrome P450 enzyme alterations in humans with progressive stages of nonalcoholic fatty liver disease.
The action of cytochrome b(5) on CYP2E1 and CYP2C19 activities requires anionic residues D58 and D65. b(5) residues D58 and D65 are essential for the stimulation of CYP2E1 and CYP2C19 activities and that the phospholipid composition significantly influences the b(5)-P450 interaction. At least two surfaces of b(5) differentially influence P450 activities, and the critical residues for individual P450 reactions cannot be predicted from sensitivity to apo-b(5) alone.
Development of HepG2-derived cells expressing cytochrome P450s for assessing metabolism-associated drug-induced liver toxicity.
Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the breakdown of lipids. This process can constitute the course of Lipidosis (normal condition).
positive regulation of lipid catabolic process [lipidosis - normal]
FAAH inhibition enhances anandamide mediated anti-tumorigenic effects in non-small cell lung cancer by downregulating the EGF/EGFR pathway.
Identification and characterization of a gene encoding human LPGAT1, an endoplasmic reticulum-associated lysophosphatidylglycerol acyltransferase.
Cholesterol homeostasis imbalance is a subtype of chemical homeostasis imbalance: A process that becomes lacking a cholesterol homeostastasis balance. This entity is a specific course-dependent process. This process can constitute the course of Niemann-Pick C.
Cholesterol homeostasis imbalance [Niemann-Pick C]
Increasing drug metabolite is a subtype of increasing quantity: A process that changes the amount of drug metabolites to be higher. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
increasing drug metabolite [Glutathione depletion]
Compound accumulation in liver is a subtype of accumulation of xenobiotics: A process that keeps compound in the liver. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
compound accumulation in liver [Glutathione depletion]
Hyperfunction of drug metabolizing enzyme gene expression is a subtype of hyperfunction of gene expression: A process that performs an excesssive drug metabolizing enzyme gene expression. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
hyperfunction of drug metabolizing enzyme gene expression [Glutathione depletion]
Hyperfunction of cutochrome P450 gene expression is a subtype of hyperfunction of drug metabolizing enzyme gene expression: A process that performs an excesssive gene expression of cytochrome p450. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
hyperfunction of Cytochrome P450 gene expression [Glutathione depletion]
hyperfunction of P450 gene expression [Glutathione depletion]
Hyperfunction of drug metabolism phase I is a subtype of hyperfunctioning of drug metabolism: A process that performs an excessive drug metabolism phase I. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
hyperfunction of drug metabolism by P450 [Glutathione depletion]
hyperfunction of drug metabolism phase I by Cytochrome P450 [Glutathione depletion]
Cytochrome P450 activation is a subtype of molecular activation: A process that changes the activity of the cytochrome P450 to be higher. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
Cytochrome P450 activation [Glutathione depletion]
NAPQI production is a subtype of generating a substance : A process that synthesizes NAPQI (N-acetyl-p-benzoquinone imine) as output. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
NAPQI production [Glutathione depletion]
cytochrome P450 (CYP) enzymes, including CYP2E1, CYP1A2, and CYP3A4, convert 5–9% of acetaminophen to a highly reactive metabolite, N-acetyl-p-benzoquinonimine (NAPQI) (Corcoran et al., 1980; Dahlin et al., 1984)
Increasing demand for glutathione conjugation is a subtype of increasing functional demand: A process changes the functional demand for the for glutathione conjugation to be higher. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
increasing demand for glutathione conjugation [Glutathione depletion]
Increasing demand for response to mitochondrial oxidative stress is a subtype of increasing the demand for response to oxidative stress: A process that changes the functional demand for the response to the mitochondrial oxidative stress to be higher. This entity is a specific course-dependent process. This process can constitute the course of Oxidative stress.
increasing demand for response to mitochondrial oxidative stres [Oxidative stress]
JNK translocation from cytoplasm to mitochondria is a subtype of transmitting: A process that of the directed movement of JNK from the cytoplasm to the mitochondria. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
chronic ethanol-induced activation of KCs is attributed to gut-sourced LPS, which is a major component of outer membrane of Gram-negative bacteria and passes through the intestinal epithelial barrier. Chronic ethanol exposure can increase translocation of LPS from gut to liver by enhancing the intestinal permeability and altering the gut microflora.
JNK translocation from cytoplasm to mitochondria [Glutathione depletion]
Any process that stops, prevents, or reduces the frequency, rate or extent of glutathione conjugation process. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
negative regulation glutathione conjugation [Glutathione depletion]
Michael acceptors such as diethyl maleate (DEA) and phorone are commonly used in vivo to deplete GSH levels in experimental animals. Casarett & Doull's Toxicology: The Basic Science of Poisons, Eighth Edition
Hypofunction of drug metabolism phase II is a subtype of hypofunction of drug metabolism: A process that performs a decreased or insufficient drug metabolism phase II. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
hypofunction of drug metabolism phase II [Glutathione depletion]
Decreasing excretion quantity of bile acid is a subtype of decreasing quantity: A process that changes the excretion quantity of of bile acids to be lower. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
decreasing excretion quantity of the conjugates [Glutathione depletion]
Glutathione conjugation (supply) - function demand imbalance is a subtype of imbalance: A process that becomes lacking a homeostastasis balance between glutathione conjugation supply and demand. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
Glutathione conjugation (supply) - function demand imbalance [Glutathione depletion]
NAPQI accumulation is a subtype of accumulation of substances in a biological object: A process that keeps NAPQI (N-acetyl-p-benzoquinone imine) within a biological object(s). NAPQI is an intermediate metabolite of the paracetamol and plays a role as a toxic substance in the body. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
NAPQI accumulation [Glutathione depletion]
Glutathione depletion is a subtype of depleting: A process that lessens markedly in the amount of glutathione. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
glutathione depletion [Glutathione depletion]
The chemical reactions and pathways resulting in the formation of glutathione, the tripeptide glutamylcysteinylglycine, which acts as a coenzyme for some enzymes and as an antioxidant in the protection of sulfhydryl groups in enzymes and other proteins. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
The formation of glutathione, the tripeptide glutamylcysteinylglycine, which acts as a coenzyme for some enzymes and as an antioxidant in the protection of sulfhydryl groups in enzymes and other protein.
glutathione biosynthetic process [Glutathione depletion]
JNK translocation from cytoplasm to mitochondria is a subtype of molecule transport: A process that of the directed movement of JNK from the cytoplasm to the mitochondria.
JNK translocation from cytoplasm to mitochondria
Protein binding by NAPQI is a subtype of protein binding: Interacting between a protein and NAPQI. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
protein binding by NAPQI [Glutathione depletion]
Malfunctioning of mitochondrial ATP synthesis coupled electron transpor is a subtype of malfunctioning process: A process that cannot perform a respiratory electron transport chain appropriately or cannot realize it at all. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
malfunctioning of mitochondrial ATP synthesis coupled electron transpor [Glutathione depletion]
Drug-, radiation-induced, or spontaneous injuries to DNA that introduce deviations from its normal double-helical conformation. These changes include structural distortions that interfere with replication and transcription, as well as point mutations that disrupt base pairs and exert damaging effects on future generations through changes in DNA sequence. If the damage is minor, it can often be repaired (DNA repair); extensive damage can induce apoptosis. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
Increasing free radical is a subtype of increasing quantity: A process that changes the amount of free radicals to be larger. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
increasing free radical [Glutathione depletion]
Lipoperoxidation is a subtype of lipid oxidation: The degradation of lipids caused by an oxidative attack from free radicals. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
lipoperoxidation [Glutathione depletion]
Increasing demand for response to mitochondrial oxidative stress is a subtype of increasing the demand for response to oxidative stress: A process that changes the functional demand for the response to the mitochondrial oxidative stress to be higher. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
increasing demand for response to mitochondrial oxidative stress [Glutathione depletion]
Mitochondrial dysfunction is a subtype of dysfunctioning: A process that performs an abnormal and incomplete mitochondrial function. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
mitochondrial dysfunction [Glutathione depletion]
Hypofunction of ATP biosynthesis is a subtype of hypofunction of biosynthesis: A process that performs a decreased or insufficient ATP biosynthesis. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
hypofunction of ATP biosynthesis [Glutathione depletion]
Any biological process that results in permanent cessation of all vital functions of a cell. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
Abnormality of membrane is a subtype of changing abnormal cellular structure: A process that changes the membrane stucture abnormally. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
abnormality of membrane [Glutathione depletion]
Calcium ion homeostasis imbalance is a subtype of chemical homeostasis imbalance: A process that becomes lacking a calcium ion homeostastasis balance. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
calcium ion homeostasis imbalance [Glutathione depletion]
Any process that increases the frequency, rate or extent of the passage or uptake of molecules by the mitochondrial membrane. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
positive regulation of mitochondrial membrane permeability [Glutathione depletion]
In the imbalance model, the basic units are as follows: 1) a functioning process (supply) for biological defense and maintaining homeostasis; 2) a functional demand process (demand) as toxic activity; 3) balance/imbalance between toxic activity and defense processes; and 4) outcome from organelles, cells, or tissues to the organ exhibiting toxicity manifestations. This entity is a compound state that inculdes step 1 to 4. This entity is a compound state that inculdes step 1 to 4. The defense performance level is Moderate (M) in daily life; however, the functional demand level is Very high (VH), which leads to the imbalance and leads to toxicity manifestation.
Aryl hydrocarbon receptor activation is a subtype of activating nuclear receptor: A process that changes the activity of the activating AhR (aryl hydrocarbon receptor) with a nuclear receptor role to be higher.
Constitutive androstane receptor activation is a subtype of activating nuclear receptor: A process that changes the activity of the activating CAR ( constitutive androstane receptor) with a nuclear receptor role to be higher.
constitutive androstane receptor activation
ATF4 gene expression regulation system is a subtype of pathway system. This entity has sub-parts and has a goal of regulating gene expressions by ATF4 as a systemic context.
Forming a complex with Cyp is a subtype of protein complex assembly: The aggregation, arrangement and bonding together with Cyp (cytochrome P450) to form a complex.
P53 activation is a subtype of activation of transcription factor: A process that changes the activity of one of the p53 family of proteins to be higher.
Retinoid X receptor activation is a subtype of activating nuclear receptor: A process that changes the activity of the RXR (retinoid X receptor) with a nuclear receptor role to be higher.
Hyperfunction of lipase gene expression is a subtype of hyperfunction of gene expression: A process that performs an excesssive lipase gene expression.
A process of liquid water accumulation in a particular location in an organism, tissue or cell.
Increasing number of apoptotic cells in liver is a subtype of increasing number of dead cells in liver: A process that becomes larger in the number of apoptotic cells in the liver.
increasing number of apoptotic cells in liver
Hyperfunction of lipase gene expression is a subtype of hyperfunction of gene expression: A process that performs an excesssive lipase gene expression. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
hyperfunction of lipase gene expression [lipidosis]
Apoptosis inducer activation is a subtype of molecular activation: A process that changes the activity of the molecule with an apoptosis inducer role to be higher.
The chemical reactions and pathways resulting in the breakdown of lipids, compounds soluble in an organic solvent but not, or sparingly, in an aqueous solvent. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
Lipid transport from liver is a subtype of lipid transport. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
lipid transport from hepatocyte to extrahepatic [lipidosis]
Positive regulation process is a subtype of controlling: A process that activates or increases the frequency, rate or extent of function.
Any process that activates, maintains or increases the rate or extent of a process.
A moving process of alcohol from the outside to the inside of a body.
A role played by the entity within a toxicity prediction context.
Hyperfunction of glucuronic acid conjugation is a subtype of hyperfunction of drug metabolism phase II: A process that performs an excessive glucuronic acid conjugation.
hyperfunction of glucuronic acid conjugation
Hyperfunction of glutathione conjugation is a subtype of hyperfunction of drug metabolism phase II: A process that performs an excessive glutathione conjugation.
hyperfunction of glutathione conjugation
Increasing hepatic vascular lumen area is a subtype of increasing area: A process that changes the area of the hepatic vascular lumen area to be larger.
Smooth endoplasmic reticulum proliferation in hepatocyte is a subtype of endoplasmic reticulum proliferation in hepatocyte: A process that becomes larger in the number of smooth endoplasmic reticulum in hepatocyte(s).
smooth endoplasmic reticulum proliferation in hepatocyte
A moving process of a tumor cell from the outside to the inside of other organ.
sequestering of triglyceride (severe) is a subtype of lipid strorage in hepatocyte: A process that keeps triglycerides in hepatocytes. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
sequestering of triglyceride (severe) [lipidosis]
Glucose homeostasis imbalance is a subtype of chemical homeostasis imbalance: A process that becomes lacking a glucose homeostastasis balance.
Phenobarbital accumulation in liver is a subtype of compound accumulation in liver: A process that keeps phenobarbital in the liver.
Carbohydrate storage in liver is a subtype of carbohydrate storage: The accumulation in hepatocytes of carbohydrates.
Hyperfunction of drug metabolism phase II is a subtype of hyperfunction of drug metabolism: A process that performs an excessive drug metabolism phase II.
hyperfunction of drug metabolism phase II
Hyperfunction of iron supply is a subtype of hyperfunctioning: A process that performs an excesssive iorn supply.
CAD accumulation in lysosome is a subtype of compound accumulation in lysosome: A process that keeps CAD (Cationic Amphiphilic Drug) in the lysosome.
CAD accumulation in lysosome is a subtype of compound accumulation in lysosome: A process that keeps CAD (Cationic Amphiphilic Drugs) in the lysosome. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (mild).
CAD accumulation in lysosome [Phospholipidosis (mild)]
Compound accumulation in lysosome is a subtype of accumulation of xenobiotics: A process that keeps compound in the lysosome.
Phospholipid homeostasis imbalance is a subtype of lipid homeostasis imbalance: A process that becomes lacking a phospholipid homeostastasis balance.
Phospholipid accumulation is a subtype of accumulation of substances in a biological object: A process that keeps phospholipid in an organism, tissue, organelle, or cell.
Increasing blood glucose lebvel is a subtype of increasing concentration: A process that changes the blood glucose concentration in the blood to be higher. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
increasing blood glucose level [ER stress]
ER stress-induced inflammation: does it aid or impede disease progression?: ER stress in various cells plays an important role in the pathogenesis of several diseases, including obesity, type 2 diabetes, cancer, and intestinal bowel and airway diseases. Moreover, it has been suggested that ER stress-induced inflammation contributes substantially to disease progression.
Hyperfunction of reduction of NAD(+) to NADH is a subtype of hyperfunction of reduction: A process that performs an excesssive reduction of NAD(+) to NADH. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
hyperfunction of reduction of NAD(+) to NADH [Lipidosis]
Increasing lysosomal pH is a subtype of changing pH: A process that changes the pH in lysosome to be higher.
Increasing demand for phospholipid degradation is a subtype of increasing functional demand: A process that changes the functional demand for the phospholipid degradation to be higher.
increasing demand for phospholipid degradation
Undigested membrane material accumulation is a subtype of accumulation of substances in a biological object: A process that keeps undigested membrane material.
undigested membrane material accumulation
Increasing phospholipid is a subtype of increasing quantity: A process that changes the amount of phospholipid to be larger.
Increasing phospholipid inflow is a subtype of increasing quantity: A process that changes the phospholipid inflow into the hepatocyte to be larger.
Mice deficient for Elovl6, the gene encoding the elongase that catalyzes the conversion of palmitate to stearate, were generated and shown to become obese and develop hepatosteatosis when fed a high-fat diet or mated to leptin-deficient ob/ob mice. However, they showed marked protection from hyperinsulinemia, hyperglycemia and hyperleptinemia. Amelioration of insulin resistance was associated with restoration of hepatic insulin receptor substrate-2 and suppression of hepatic protein kinase C epsilon activity resulting in restoration of Akt phosphorylation.
Hypofunction of phospholipid degradation is a subtype of hypofunction of decomposing: A process that performs a decreased or insufficient phospholipid degradation.
hypofunction of phospholipid degradation
Forming a complex of drugs and biological substance is a subtype of protein complex assembly: The aggregation, arrangement and bonding together between drugs and biological molecules to form a complex.
forming a complex of drugs and biological substance
Increase in alcohol inflow into hepatocyte is a subtype of increasing quantity: A process that changes the alcohol inflow into the hepatocyte to be larger.
increase in alcohol inflow into hepatocyte
Negative regulation of phospholipid degradation is a subtype of negative regulation of decomposing: A process that stops, prevents, or reduces the frequency, rate or extent of phospholipid degradation.
negative regulation of phospholipid degradation
Hyperfunction of dead cell phagocytosis by Kupffer cells (macrophages) is a subtype of hyperfunctioning: A process that performs phagocytosis of dead cells by Kupffer cells or macrophages execessively. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense).
hyperfunction of dead cell phagocytosis by Kupffer cells (macrophages) [Phospholipidosis (excessive defense)]
Any process that stops, prevents, or reduces the frequency, rate or extent of lysophagy.
Increasing uptake amount of mitochondrial calcium ion is a subtype of increasing quantity: A process that changes the uptake amount of mitochondrial calcium ion to be higher. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
increasing uptake amount of mitochondrial calcium [Lipidosis]
Forming a complex of CAD and phospholipid is a subtype of forming a complex of drugs and biological substance: A process that forms a complex consisiting phospholipids and CAD (Cationic Amphiphilic Drugs cationic amphiphile drug) in the lysosomal membrane, which causes structural change of the membrane. The degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (moderate).
forming a complex of CAD and phospholipid [Phospholipidosis (moderate) ]
Hypofunction of phospholipid export from lysosome is a subtype of hypofunction of export: A process that performs a decreased or insufficient phospholipid export from lysosome.
hypofunction of phospholipid export from lysosome
Hypofunction of phospholipid export from lysosome is a subtype of hypofunction of export: A process that performs a decreased or insufficient phospholipid export from lysosome. And the degree is severe. This process can constitute the course of Phospholipidosis (severe).
hypofunction of phospholipid export from lysosome [Phospholipidosis (severe) ]
Changing balance of phospholipid metabolism is a subtype of changing balance: A process that changes the balance between phospholipid anabolism and catabolism.
changing balance of phospholipid metabolism
Hyperfunction of glycerophospholipid synthesis gene expression is a subtype of hyperfunction of phospholipid synthesis gene expression: A process that performs an excesssive glycerophospholipid synthestic gene expression.
hyperfunction of glycerophospholipid synthesis gene expression
Lipid storage in liver is a subtype of lipid storage: The accumulation and maintenance in cells or tissues of lipids in the liver. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
Carbohydrate storage in liver is a subtype of carbohydrate storage: The accumulation in hepatocytes of carbohydrates. This entity is a specific course-dependent process. This process can constitute the course of Hypertrophy.
carbohydrate storage in liver [Hypertrophy]
Moving lipid to the hepatocyte is a subtype of moving A to the inside of B: A process of the movement of lipid into a hepatocyte. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
moving lipid to the hepatocyte [lipidosis]
Malfunctioning of TCA cycle is a subtype of malfunctioning of metabolism: A process that cannot perform a tricarboxylic acid cycle appropriately or cannot realize it at all. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
Malfunctioning of TCA cycle is a subtype of malfunctioning of metabolism: A process that cannot perform a tricarboxylic acid cycle appropriately or cannot realize it at all.
Moving lipid to the hepatocye is a subtype of moving A to the inside of B: A process of the movement of lipid into a hepatocyte.
The directed movement of lipid, out of a hepatocyte.
Hyperfunction of alcohol metabolism is a subtype of hyperfunctioning: A process that performs an excessive alcohol metabolism.
Increaseing production quantity of catecholamine is a subtype of increasing quantity: A process that changes the production amount of catecholamine to be higher. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
increaseing production quantity of catecholamine [lipidosis]
Catalysis role of the reaction: ATP + ethanolamine = ADP + 2 H(+) + phosphoethanolamine.
related molecular function GO:0004305 ethanolamine kinase activity
Lipid storage in liver is a subtype of lipid storage: The accumulation and maintenance in cells or tissues of lipids in the liver.
The totality of all processes through which cholestasis is realized.
BSEP inhibition : bosentan, cyclosporin, glibenclamide, rifampicin, rifamycin
This entity is under construction. Drug induced liver injury (DILI) is categorized as drug induced cholestasis (DIC), drug-induced hepatitis, and is mixed liver injury. Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS). phallodin, microsystin, amantin is facilitated by the uptake thpugh OATPs. rifampicin, bosentan, troglitazone directly inhibit BSEP.
Impairment of bile flow due to injury to the the canalicular bile ducts.
Impairment of bile flow due to injury to the the intrahepatic bile ducts.
Eosinogranular degeneration dependent molecule is a subtype of toxic course dependent chemical entity. This gene can participate in the course of eosinogranular degeneration as a gene product. Gene profile:caonical that described in textbooks or articles.
eosinogranular degeneration dependent molecule (canonical)
The non-covalent aggregation and arrangement of proteins and lipids in the liver to form a very-low-density lipoprotein particle. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
NRF2 activation is a subtype of activation of transcription factor: A process that changes the activity of NRF2 (Nuclear Factor, Erythroid 2 Like 2) to be higher.
CD36 activation is a subtype of molecular activation: A process that changes the activity of the CD36 to be higher. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
Increased hepatic CD36 expression contributes to dyslipidemia associated with diet-induced obesity. During diet-induced obesity, CD36 protein levels in the liver are significantly elevated, and these elevated levels correlate with increased hepatic triglyceride storage and secretion. These alterations in liver lipid storage and secretion were also observed upon forced expression of hepatic CD36 in the absence of DIO and were accompanied with a marked rise in hepatic fatty acid uptake in vivo, demonstrating that increased CD36 expression is sufficient to recapitulate the aberrant liver lipid handling observed in DIO.
Scavenger receptors class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages.
Liver dysfunction is a subtype of dysfunctioning: A process that performs an abnormal and incomplete liver function. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
liver dysfunction [Phospholipidosis (severe) ]
Obesity is a subtype of increasing weight: A process that changes the body weight to be higher.
Hypofunction of phosphosphingolipid degradation is a subtype of hypofunction of phospholipid degradation: A process that performs a decreased or insufficient phosphosphingolipid degradation.
hypofunction of phosphosphingolipid degradation
Hyperfunction of reduction of NAD(+) to NADH is a subtype of hyperfunction of reduction: A process that performs an excesssive reduction of NAD(+) to NADH. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
hyperfunction of reduction of NAD(+) to NADH [Fibrosis]
Increasing NAD/NAD+ ratio is a subtype of increasing ratio: A process that changes the ratio of NAD to NAD+ to be higher. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
Hyperfunction of sphingophospholipid synthesis gene expression is a subtype of hyperfunction of phospholipid synthesis gene expression: A process that performs an excesssive sphingophospholipid synthetic gene expression.
hyperfunction of sphingophospholipid synthesis gene expression
The chemical reactions and pathways resulting in the formation of phosphosphingolipids.
Increasing NAD/NAD+ ratio is a subtype of increasing ratio: A process that changes the ratio of NAD to NAD+ to be higher.
Sphingophopholipid metabolism imbalance is a subtype of phospholipid metabolism imbalance: A process that becomes lacking a homeostastasis balance of sphingophopholipid metabolism.
Any process that stops, prevents, or reduces the frequency, rate or extent of lysophagy. This entity is a specific course-dependent process. This process can constitute the course of phospholipidosis (severe).
negative regulation of lysophagy [Phospholipidosis (severe)]
Glycerophospholipid metabolism imbalance is a subtype of phospholipid metabolism imbalance: A process that becomes lacking a homeostastasis balance of glycerophospholipid metabolism.
glycerophospholipid metabolism imbalance
increasing number of damaged lysosomes is a subtype of increasing number : A process that becomes larger in the number of damaged lysosomes.
Hypofunction of maintaining lysosome homeostasis is a subtype of hypofunctioning: A process that performs a decreased or insufficient maintaining lysosome homeostasis.
hypofunction of maintaining lysosome homeostasis
The cellular catabolic process in which cells digest parts of their own cytoplasm; allows for both recycling of macromolecular constituents under conditions of cellular stress and remodeling the intracellular structure for cell differentiation This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
An attribute that inheres in a bearer by virtue of network
Refolding promoting gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature refolding inducing gene product or products (proteins or RNA) .
Hepatic lipid composition and stearoyl-coenzyme A desaturase 1 mRNA expression can be estimated from plasma VLDL fatty acid ratios.
Remarkably, liver stearoyl-CoA desaturase (Scd) mRNA expression was by far the most highly-induced transcript in WD-fed rats (approximately 30-fold, FDR = 0.01) which supports previous literature underscoring this gene as a crucial target during NAFLD development.
Hyperfunction of reduction of NAD(+) to NADH is a subtype of hyperfunction of reduction: A process that performs an excesssive reduction of NAD(+) to NADH.
hyperfunction of reduction of NAD(+) to NADH
Negative regulation of glycerophospholipid degradation is a subtype of negative regulation of phospholipid degradation: A process that stops, prevents, or reduces the frequency, rate or extent of glycerophospholipid degradation.
negative regulation of glycerophospholipid degradation
Increasing acetyl CoA is a subtype of increasing quantity: A process that changes the amount of acetyl CoA to be larger. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
ATF6 (ATF6-alpha) activates chaperone genes is a subtype of molecular activation: A process that changes the activity of the molecule with chaperone role to be higher by ATF6. This process is dependent on the refolding and can constitute the course of ER stress.
ATF6 (ATF6-alpha) activates chaperone genes [ER stress - refolding]
A role played by the entity which enables the transfer of choline from one side of a membrane to the other. Choline (2-hydroxyethyltrimethylammonium) is an amino alcohol that occurs widely in living organisms as a constituent of certain types of phospholipids and in the neurotransmitter acetylcholine.
CD36 activation is a subtype of molecular activation: A process that changes the activity of the CD36 to be higher.
Targeting metastasis-initiating cells through the fatty acid receptor CD36.
Hypofunction of fatty acid beta-oxidation is a subtype of hypofunction of fatty acid oxidation: A process that performs a decreased or insufficient fatty acid beta-oxidation. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
hypofunction of fatty acid beta-oxidation [Fibrosis]
Any process that stops, prevents, or reduces the frequency, rate or extent of the regulated release of insulin. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
negative regulation of insulin secretion [ER stress]
AP-1 activation is a subtype of molecular activation: A process that changes the activity of the AP-1 to be higher.
Increasing phospholipid material is a subtype of increasing quantity: A process that changes the amount of phospholipid material to be larger.
Increasing phospholipid material is a subtype of increasing quantity: A process that changes the amount of phospholipid material to be larger. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
increasing phospholipid material [Phospholipidosis (severe)]
A role played by the entity to change the molecule (activity).
Increasing glycerophospholipid material is a subtype of increasing materials for lipid formation: A process that changes the amount of glycerophospholipid material to be larger.
Increasing glycerophospholipid material is a subtype of increasing materials for lipid formation: A process that changes the amount of glycerophospholipid material to be larger. This process is dependent on the glycerophospholipid disorder (severe) and can constitute the course of Phospholipidosis.
increasing glycerophospholipid material [phospholipidosis - glycerophospholipid disorder (severe)]
Lipid metabolism and liver inflammation. I. Hepatic fatty acid uptake: possible role in steatosis.
Hepatic fatty acid transporter Cd36 is a common target of LXR, PXR, and PPARgamma in promoting steatosis. Activation of LXR induced Cd36. Moreover, the hepatic steatosis induced by LXR agonists was largely abolished in Cd36 null mice. PXR can regulate Cd36 directly or through its activation of PPARgamma. Both LXR-mediated Cd36 regulation and PXR-mediated PPARgamma regulation are liver specific.
AMPK activation promotes fatty acid uptake into the cell through the fatty acid transporter FAT/CD36 in addition to its stimulating role on mitochondrial fatty acid oxidation.
VPA enhanced oleic acid- (OLA-) induced lipid accumulation in a dose-dependent manner in hepatocytes; this may be due to upregulated lipid uptake, triacylglycerol (TAG) synthesis, and lipid droplet formation. Following VPA treatment, the expression levels of genes encoding cluster of differentiation 36 (Cd36), low-density lipoprotein receptor-related protein 1 (Lrp1), diacylglycerol acyltransferase 2 (Dgat2), and perilipin 2 (Plin2) were increased. CD36 regulates lipid uptake in different cells via binding to different ligands including long-chain fatty acids and native/oxidized lipoproteins. Increased hepatic CD36 expression is highly correlated with human insulin resistance and nonalcoholic steatohepatitis (NASH) development
The directed movement of choline into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. Choline (2-hydroxyethyltrimethylammonium) is an amino alcohol that occurs widely in living organisms as a constituent of certain types of phospholipids and in the neurotransmitter acetylcholine. This process is dependent on the phosphatidylcholine disorder and can constitute the course of Phospholipidosis.
choline transport [Phospholipidosis - phosphatidylcholine disorder]
AP-1 activation is a subtype of AP-1 activation: A process that changes the activity of the AP-1 to be higher by JNK.
AP-1 activation is a subtype of AP-1 activation: A process that changes the activity of the AP-1 to be higher by JNK. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Hypofunction of hepatic metabolism is a subtype of hypofunction of metabolism: A process that performs a decreased or insufficient hepatic metabolism.
Hypofunction of protein metabolism is a subtype of hypofunction of metabolism: A process that performs a decreased or insufficient protein metabolism.
Hypofunction of lipid metabolism is a subtype of hypofunction of metabolism: A process that performs a decreased or insufficient lipid metabolism.
Hypofunction of carbohydrate metabolism is a subtype of hypofunction of metabolism: A process that performs a decreased or insufficient carbohydrate metabolism.
Hypofunction of cholesterol biosynthesis is a subtype of hypofunction of lipid biosynthesis: A process that performs a decreased or insufficient cholesterol biosynthesis.
hypofunction of cholesterol biosynthesis
Peroxisome Proliferator-Activated Receptor Alpha [Eosinophilic granular degeneration]
PPARA (canonical)[Eosinophilic granular degeneration]
Decreasing cholesterol concentration in blood is a subtype of decreasing concentration: A process that changes the concentration of the cholesterol in the blood to be lower.
decreasing cholesterol concentration in blood
Hypofunction of albumin biosynthesis is a subtype of hypofunction of biosynthesis: A process that performs a decreased or insufficient albumin biosynthesis.
Decreasing albumin concentration in blood is a subtype of decreasing concentration: A process that changes the concentration of the albumin in the blood to be lower.
decreasing albumin concentration in blood
Decreasing blood osmotic pressure. is a subtype of decreasing osmotic pressure.: A process that changes the osmotic pressure to be lower.
An attribute inhering in a bearer by virtue of the bearer's participation in movement.
Decreasing amount of circulating blood is a subtype of decreasing blood flow: A process that changes the amount of circulating blood to be smaller.
Decreasing renal blood flow is a subtype of decreasing flow: A process that changes the amount of renal flow to be lower.
Increasing creatinine concentration is a subtype of increasing concentration: A process that changes the creatinine concentration to be higher.
Renin-angiotensin activation is a subtype of activating: A process that changes the activity of the renin-angiotensin system, which regulates blood pressure and fluid balance, to be higher.
A class of lipoproteins of small size (18-25 nm) and low density (1.019-1.063 g/ml) particles with a core composed mainly of cholesterol esters and smaller amounts of triglycerides. The surface monolayer consists mostly of phospholipids, a single copy of apolipoprotein B-100, and free cholesterol molecules. The main function of LDL is to transport cholesterol and cholesterol esters from the liver. Excessive levels are associated with cardiovascular disease.
Hypofunction of retinol storage is a subtype of hypofunctioning: A process that performs a decreased or insufficient retinol storage.
A role played by the molecule which transfers fatty acids.
Hypofunction of liver's excretion is a subtype of hypofunction of removing: A process that performs a decreased or insufficient liver's excretion.
Bile acid biosynthetic malfunction is a subtype of organ malfunction: A process that does not perform a bile acid biosynthetic function correctly.
Bile secretion malfunction is a subtype of organ malfunction: A process that does not perform bile secretion function correctly.
Cholestasis (primitive process) is a subtype of stagnating: A process that changes the bile flow to be slower due to obstruction.
Inreasing blood ALP concentration is a subtype of increasing concentration: A process that changes the bilirubin concentration in the blood to be higher.
Increasing γ-glutamyltransferase concentration in blood is a subtype of increasing concentration: A process that changes the γ-glutamyltransferase (GGT) concentration to be higher.
increasing γ-glutamyltransferase concentration in blood
Hypofunction of bilirubin excretion is a subtype of hypofunction of liver's excretion: A process that performs a decreased or insufficient bilirubin excretion.
Increasing bilirubin concentration in blood is a subtype of increasing concentration: A process that changes the bilirubin concentration in the blood to be higher.
increasing bilirubin concentration in blood
Jaundice is a changing process that generally changes the color of the skin or eyes into yellow.
Hypofunction of blood coagulation factor synthesis is a subtype of hypofunction of biosynthesis: A process that performs a decreased or insufficient blood coagulation factor synthesis.
hypofunction of blood coagulation factor synthesis
Hypofunction of detoxification is a subtype of hypofunctioning: A process that performs a decreased or insufficient detoxification.
Increasing ammonia concentration in blood is a subtype of increasing concentration: A process that changes the ammonia concentration in the blood to be higher.
increasing ammonia concentration in blood
The directed movement of VLDL, out of a hepatocyte.
The totality of all processes through which hepatic vascular circulation disorder is realized.
hepatic vascular circulation disorder (toxic course)
Hepatic shunt formtion is a subtype of biological structure formation: A process that makes abnormal communications between the hepatic arteries, portal veins, and hepatic or systemic veins.
It makes abnormal communications between the hepatic arteries, portal veins, and hepatic or systemic veins.
Increasing hepatic portal pressure is a subtype of increasing pressure: A process that changes the hepatic portal pressure to be higher.
Inzreasing size of the spleen is a subtype of increasing size: A process that changes the size of the of the spleen to be larger.
Spleen hyperfunction is a subtype of hyperfunctioning: A process that performs an excessive spleen function.
Decreasing hemoglobin concentration in blood is a subtype of decreasing concentration: A process that changes the concentration of the hemoglobin in the blood to be lower.
decreasing hemoglobin concentration in blood
Bypass formation is a subtype of biological structure formation: A process that constructs an alternate passage of a bodily substancepassage carrying blood.
Varicosity of veins formation is a subtype of biological structure formation: A process that have a varicosity of veins.
Stomach congestion is a subtype of hyperfunctioning of accumulation: A process that performs an excessive accumulation of blood in the stomach.
Increasing hepatic venous pressure is a subtype of increasing pressure: A process that changes the hpatic venous pressure to be higher.
Hyperfunction of hepatic lymph production is a subtype of hyperfunction of biosynthesis: A process that performs an excessive hepatic lymph production.
hyperfunction of hepatic lymph production
Hepatic lymph leakage is a subtype of leaking: A process that leaks lymph out from the liver lymphatic vessel.
Ascites (process) is a subtype of accumulation of fluids: A process that keeps fluid in the peritoneal cavity.
NRF2 activation by PERK is a subtype of NRF2 activation: A process that changes the activity of NRF2 (Nuclear Factor, Erythroid 2 Like 2) to be higher by PERK.
The directed movement of VLDL, out of a hepatocyte. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
VLDL release from hepatocyte [Lipidosis]
Increasing aldosterone concentration in blood is a subtype of increasing concentration: A process that changes the aldosterone concentration in the blood to be higher.
increasing aldosterone concentration in blood
A role played by a chemical compound exihibiting itself through the ability to induce damage to the kidney in animals.
Edema is a subtype of accumulation of fluids: A process that keeps an excessive fluid in cells or intercellular tissues.
Edema may be related to one or more of the following factors: 1) increased capillary hydrostatic pressure, 2) decreased osmotic pressure of plasma, 3) decreased tissue tension and lymphatic drainage, 4) increased osmotic pressure of tissue fluids, and 5) increased capillary permeability.
Hypofunction of hormone metabolic process is a subtype of hypofunction of metabolism: A process that performs a decreased or insufficient hormone metabolic process.
hypofunction of hormone metabolic process
Hypofunction of estrogen degradation is a subtype of hypofunction of decomposing: A process that performs a decreased or insufficient estrogen degradation.
Increasing estrogen concentration in blood is a subtype of increasing concentration: A process that changes the estrogen concentration in the blood to be higher.
increasing estrogen concentration in blood
Hyperfunction of glutathione synthetic gene expression is a subtype of hyperfunction of gene expression: A process that performs an excesssive glutathione synthetic gene expression.
hyperfunction of glutathione synthetic gene expression
Lipid degradtion related gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature lipid degradation related gene product or products (proteins or RNA). This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
lipid degradation related gene expression [lipidosis]
Leaking fluid from blood vessel is a subtype of leaking: A process that leaks fluid out from the blood vessel.
Lipid degradtion related gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature lipid degradation related gene product or products (proteins or RNA).
lipid degradation related gene expression
Lipid synthesis gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature lipid synthesis gene product or products (proteins or RNA).
MMP inactivation by TIMP1 is a subtype of inactivating: A process that changes the activity of the MMP to be lower by TIMP1.
Catalysis role of the transfer of an acyl group from one compound (donor) to another (acceptor).
Lipid synthesis gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature lipid synthesis gene product or products (proteins or RNA). This entity is a specific course-dependent process. This process can constitute the course of Lipidosis."
lipid synthesis gene expression [lipidosis]
Fatty acid strorage is a subtype of accumulation of substances in a biological object: A process that keeps fatty acid in a biological object. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
A fatty acid oxidation process that results in the complete oxidation of a long-chain fatty acid in the mitochondria. Fatty acid beta-oxidation begins with the addition of coenzyme A to a fatty acid, and occurs by successive cycles of reactions during each of which the fatty acid is shortened by a two-carbon fragment removed as acetyl coenzyme A; the cycle continues until only two or three carbons remain (as acetyl-CoA or propionyl-CoA respectively).
Negative regulation of lipid transport from liver to peripheral tissue is a subtype of negative regulation of lipid transport: A process that stops, prevents, or reduces the frequency, rate or extent of lipid transport from liver to peripheral tissue. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
negative regulation of lipid transport from liver to peripheral tissue [Fibrosis]
A fatty acid oxidation process that results in the complete beta oxidation of a fatty acid in the mitochondria. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
mitochondrial fatty acid beta-oxidation [lipidosis]
Negative regulation of lipid transport is a subtype of negative regulation of transport: Any process that stops, prevents, or reduces the frequency, rate or extent of the directed movement of lipids into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
Bcl2 phosphorylation is a subtype of phosphorylation: A process that The process of introducing a phosphate group into Bcl2.
A role played by the entity which transmits from A to B.
FATTY Acid Synthase (canonical)[lipidosis]
ASAH1 (human)[Phospholipidosis - tumor cell proliferation induction]
An imaging assay that utilizes a microscope to magnify features of the visualized material of interest that are not visible to naked eye.
Catalysis role of the reaction: acetyl-CoA + histone = CoA + acetyl-histone.
CAD insertion into phospholipase binding site to lysosomal inner membrane is a subtype of binding: A process that CAD inserts and replaces the phospholipase binding site in the lysosomal inner membrane.
Under normal conditions, lysosomal phospholipase A2 is bound through electrostatic charge interactions to the inner membranes of the lysosome. A cationic amphiphile, accumulates in the lysosome and inserts into the inner membrane decreasing or eliminating the anionic binding sites for the lipase. The lipase is no longer able to bind to its substrates and is potentially susceptible to degradation by lysosomal proteases.
CAD insertion into phospholipase binding site to lysosomal inner membrane
CAD insertion into phospholipase binding site to lysosomal inner membrane is a subtype of binding: A process that CAD inserts and replaces the phospholipase binding site in the lysosomal inner membrane. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
CAD insertion into phospholipase binding site to lysosomal inner membrane [Phospholipidosis]
increasing number of damaged lysosomes is a subtype of increasing number : A process that becomes larger in the number of damaged lysosomes. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe) .
increasing number of damaged lysosomes[Phospholipidosis (severe)]
Negative regulation of phospholipid binding is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of phospholipid binding.
negative regulation of phospholipid binding
Negative regulation of phospholipase-mediated phospholipid degradation by CAD is a subtype of negative regulation of phospholipid degradation: A process that stops, prevents, or reduces the frequency, rate or extent of phospholipase-mediated phospholipid deradation regulated by CAD. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (mild).
negative regulation of phospholipase-mediated phospholipid degradation by CAD [Phospholipidosis (mild)]
Negative regulation of phospholipase binding to phospholipid by CAD is a subtype of negative regulation of phospholipid binding: A process that stops, prevents, or reduces the frequency, rate or extent of phosphholipid binding by phospholipase.
negative regulation of phospholipase binding to phospholipid by CAD
Increasing DGAT1, ACAT1, or ACAT2 expression in McA-RH7777 cells stimulates the assembly and secretion of VLDL from liver cells
The increased hepatic triacylglycerol level after tamoxifen treatment was accompanied by decreased acetyl-coenzyme A carboxylase (ACC) and FAS activities, increased glycerol-3-phosphate acyltransferase (GPAT) activity, and a tendency to increased diacylglycerol acyltransferase (DGAT) activity.
The chemical reactions and pathways resulting in the breakdown of phospholipids, any lipid containing phosphoric acid as a mono- or diester. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
phospholipid catabolic process [Phospholipidosis]
Negative regulation of lipid transport from liver to peripheral tissue is a subtype of negative regulation of lipid transport: A process that stops, prevents, or reduces the frequency, rate or extent of lipid transport from liver to peripheral tissue.
negative regulation of lipid transport from liver to peripheral tissue
Increasing production amount of acetaldehyde is a subtype of increasing quantity: A process that changes the production amount of acetaldehyde to be higher. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
increasing production amount of acetaldehyde [Fibrosis]
Increasing production amount of acetaldehyde is a subtype of increasing quantity: A process that changes the production amount of acetaldehyde to be higher.
increasing production amount of acetaldehyde
Hyperfunction of phospholipid biosynthesis is a subtype of hyperfunction of biosynthesis: A process that performs an excessive phospholipid biosynthesis.
hyperfunction of phospholipid biosynthesis
Hyperfunction of glycerophospholipid biosynthesis is a subtype of hyperfunction of phospholipid biosynthesis: A process that performs an excessive glycerophospholipid biosynthesis.
hyperfunction of glycerophospholipid biosynthesis
Increasing number of macrophage derived foam cell is a subtype of increasing number of objects: A process that becomes larger in the number of foam cell, a type of macrophage containing lipids in small vacuoles, in the liver.
increasing number of macrophage derived foam cell
Hypofunction of ceramide synthesis is a subtype of hypofunction of lipid biosynthesis: A process that performs a decreased or insufficient ceramide biosynthesis.
eIF2a translation regulation system is a subtype of pathway system. This entity has sub-parts and has a goal of regulating translation by eIF2a as a systemic context.
Hyperfunction of choline transport is a subtype of hyperfunction of transport: A process that performs an excesssive choline transport.
Hyperfunction of choline transport is a subtype of hyperfunction of choline transport: A process that performs an excesssive choline transport. And the degree is severe. This process is dependent on the phosphatidylcholine disorder (severe) and can constitute the course of Phospholipidosis.
hyperfunction of choline transport [Phospholipidosis - phosphatidylcholine disorder (severe) ]
Hypofunction of glycerophospholipid degradation is a subtype of hypofunction of phospholipid degradation: A process that performs a decreased or insufficient glycerophospholipid degradation.
hypofunction of glycerophospholipid degradation
Increaseing production quantity of catecholamine is a subtype of increasing quantity: A process that changes the production amount of catecholamine to be higher. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
increaseing production quantity of catecholamine [Fibrosis]
Hypofunction of phosphatidylcholine degradation is a subtype of hypofunction of glycerophospholipid degradation: A process that performs a decreased or insufficient phosphatidylserine degradation.
hypofunction of phosphatidylcholine degradation
Increaseing production quantity of catecholamine is a subtype of increasing quantity: A process that changes the production amount of catecholamine to be higher.
increaseing production quantity of catecholamine
Heoatocyte growth is a subtype of cell growth: A process that The process in which a hepatocyte, the main structural component of the liver, increases in size. This entity is a specific course-dependent process. This process can constitute the course of Hypertrophy.
gentamicin_phospholipase inhibitor [Phospholipidosis]
While amiodarone was bound to the hydrophobic part, chlorphentermine and gentamicin displayed a strong affinity for the hydrophilic part, whereas chloroquine did not bind to either site of the phospholipid molecule. Gentamicin inhibited the phosphatidylcholine and phosphatidylserine specific variants of phospholipase C, and chlorphentermine inhibited a phosphatidylinositol specific phospholipase C.
Biochemical mechanism of aminoglycoside-induced inhibition of phosphatidylcholine hydrolysis by lysosomal phospholipases. Biochem Pharmacol. 1988, 37(4):591-9. Gentamicin and bis(beta-diethylaminoethylether)hexestrol (DEH), a cationic amphiphile which also binds to phospholipid bilayers, are equipotent inhibitors when added to negatively-charged liposomes at equinormal concentrations. Although direct aminoglycoside-enzyme interactions cannot be excluded, these results strongly suggest that gentamicin impairs the activities of the lysosomal phospholipases towards phosphatidylcholine by decreasing the available negative charges required for optimal activity.
Arole played by the entity that has both hydrophobic and hydrophilic properties with a charged cationic amine group.
CADs exhibit the property of lysosomotropism, the property of a molecule to specifically associate with lysosomes. In theory, CADs could enter the lysosome through endocytosis, autophagy, or a drug-specific transporter. However, passive diffusion has been invoked as the major mechanism whereby CADs accumulate within the lysosome . CADs bind directly to phospholipids to result in indigestible drug–lipid complexes, which accumulate and are stored in the form of lysosomal lamellar bodies. Production of lamellar bodies was associated with inhibition of phospholipase activity; either due to direct inhibition or interaction of CAD at the phospholipid bilayer of the lysosome.
Cationic amphiphilic drug-induced phospholipidosis. Xenobiotics or their metabolites that induce phospholipidosis. Each of these drugs shares several common physiochemical properties: hydrophobic ring structure on the molecule and a hydrophilic side chain with a charged cationic amine group, hence the class term cationic amphiphilic drugs (CADs). The hydrophobic structure enhances the molecule’s ability pass through plasma membranes when are they to not ionized.
The multiplication or reproduction of cells, resulting in the rapid expansion of a cell population. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
ATP Binding Cassette Subfamily A Member 1 [lipidosis]
CHOP gene expression regulation system is a subtype of pathway system. This entity has sub-parts and has a goal of regulating gene expressions by CHOP as a systemic context.
Hyperfunction of phospholipid degradation is a subtype of hyperfunction of decompoing: A process that performs an excessive phospholipid degradation.
hyperfunction of phospholipid degradation
Hyperfunction of phospholipid degradation is a subtype of hyperfunction of phospholipid degradation: A process that performs excessive phospholipid degradation as an excessive defense. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense).
hyperfunction of phospholipid degradation [Phospholipidosis (excessive defense)]
The totality of all processes through which ground glass appearance is realized.
TCPOBOP and CITCO are potent direct activators of CAR. TCBOBOP is a potent agonist for mouse CAR, whereas CITCO is a potent agonist for human CAR. Casarett and Doull's
Phenobarbitone and other microsomal drug-metabolizing enzyme inducers induce hepatocyte hypertrophy through sER proliferation. This results in the characteristic eosinophilic ‘‘ground glass’’ appearance of hepatocyte cytoplasm.
Dysfunction of protein refolding is a subtype of dysfunctioning: A process that performs an abnormal and incomplete protein refolding.
Phospholipid metabolism balance is a subtype of maintaining balance: A process that keeps a balance of phospholipid metabolism.
Phospholipid metabolism balance is a subtype of maintaining balance: A process that keeps a balance of phospholipid metabolism. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (normal condition).
phospholipid metabolism balance [phopholipidosis - normal]
ATF6 gene expression regulation system is a subtype of pathway system. This entity has sub-parts and has a goal of regulating gene expressions by ATF6 as a systemic context.
The totality of all processes through which the phospholipidosis is realized. This causal process is heredity.
Loss of phospholipid degradation is a subtype of loss of function (process): A process that results in no longer having a phospholipid degradation function or the process that gradually loses it.
Loss of phospholipid degradation is a subtype of loss of function (process): A process that results in no longer having a phospholipid degradation function or the process that gradually loses it. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
loss of phospholipid degradation [Phospholipidosis]
Loss of structure is a subtype of changing structure: A process that lacks the structure or decreases structural parts.
Genetic defect is a subtype of structural defect: A process in which a part of a chromosome or a sequence of DNA is lost during DNA replication.
ATP Binding Cassette Subfamily A Member 1
Phopholipase gene mutation is a subtype of gene mutation: A process thatchanges the sequence of a phospholipase gene.
Sphingomyelinase gene mutation is a subtype of phopholipase gene mutation: A process that changes the sequence of a sphingomyelinase gene.
Sphingomyelinase gene mutation is a subtype of phopholipase gene mutation: A process that changes the sequence of a sphingomyelinase gene. This entity is a specific course-dependent process. This process can constitute the course of Niemann Pick Disease Type A/ B.
sphingomyelinase gene mutation [Niemann Pick Disease Type A/ B]
Dysfunction of phospholipid degradation is a subtype of dysfunctioning: A process that performs an abnormal and incomplete phospholipid degradation.
Dysfunction of phospholipid degradation is a subtype of dysfunctioning: A process that performs an abnormal and incomplete phospholipid degradation. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
dysfunction of phospholipid degradation [Phospholipidosis]
Cell rupture is the tearing apart of a cell. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
Hypofunction of mitochondrial fatty acid beta-oxidation is a subtype of hypofunction of fatty acid beta-oxidation: A process that performs a decreased or insufficient mitochondrial fatty acid beta-oxidation. This entity is a specific course-dependent process. This process can constitute the course of glutathione depletion.
hypofunction of mitochondrial fatty acid beta-oxidation [Glutathione depletion]
A role played by the entity which enables the directed movement of cholesterol into, out of or within a cell, or between cells.
High intakes of choline and betaine reduce breast cancer mortality in a population-based study.
Folate and choline metabolism gene variants and development of uterine cervical carcinoma.
Malfunctioning of intracellular signal transduction is a subtype of malfunctioning process: A process that cannot perform signaling [biological] appropriately or cannot realize it at all.
malfunctioning of intracellular signal transduction
Malfunctioning of receptor function is a subtype of malfunctioning process: A process that cannot perform a receiving function appropriately or cannot realize it at all.
Any process that activates, maintains or increases the rate of autophagy. Autophagy is the process in which cells digest parts of their own cytoplasm. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
positive regulation of autophagy [ER stress]
Blocking autophagy enhances meloxicam lethality to hepatocellular carcinoma by promotion of endoplasmic reticulum stress. Blocking autophagy by 3-methyladenine (3-MA) or Atg5 siRNA knock-down enhanced meloxicam lethality for HCC by activation of ER stress-related apoptosis. In addition, GRP78 seemed to lead to autophagic activation via the AMPK-mTOR signalling pathway. Blocking AMPK with a chemical inhibitor inhibited autophagy suggesting that meloxicam-regulated autophagy requires activation of AMPK. ER stress and autophagy were involved in cell death evoked by meloxicam in HCC cells. This inhibition of autophagy to enhance meloxicam lethality, suggests a novel therapeutic strategy against HCC.
Changing membrane potential is a subtype of changing quality: A process that changes the electrical potential across a membrane.
A release process of the cholesterol from hepatocyte. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
cholesterol efflux from hepatoyte [Lipidosis]
Hypofunction of cholesterol transport from hepatocyte is a subtype of hypofunction of transport: A process that performs a decreased or insufficient cholesterol transport from hepatocyte. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
hypofunction of cholesterol export from hepatoyte [lipidosis]
A value in comparison to something else.
A value which is greater in comparison to something else.
The totality of all processes through which the Niemann–Pick disease type A or type B is realized. This causal process is heredity.
Niemann–Pick disease type A and type B are inherited as autosomal recessive deficiency of the enzyme sphingomyelinase, in the lysosomes of the reticuloendothelial system. This results in the lysosomal storage of sphingomyelin. The liver and spleen are predominantly involved. Sherlock's Diseases of the Liver and Biliary System, 12th Edition
course of Niemann–Pick disease type A and type B
Hsp70 stabilizes lysosomes and reverts Niemann-Pick disease-associated lysosomal pathology.
Phopholipase gene mutation is a subtype of gene mutation: A process thatchanges the sequence of a phospholipase gene. This process is dependent on the genetic and can constitute the course of Phospholipidosis (genetic).
phopholipase gene mutation [Phospholipidosis - genetic]
Sphingomyelin Phosphodiesterase 1 [Phospholipidosis]
The chemical reactions and pathways resulting in the breakdown of sphingophospholipids.
Moving fatty axid to the hepatocyte is a subtype of moving A to the inside of B: A process of the movement of fatty acid into a hepatocyte.
Increaing in fatty acid inflow into hepatocyte is a subtype of increasing quantity: A process that changes the fatty acid inflow into the hepatocyte to be larger. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
increaing in fatty acid inflow into hepatocyte [Fibrosis]
The totality of all processes through which the Niemann–Pick disease type A is realized. This causal process is heredity.
Natural history of type A Niemann-Pick disease: possible endpoints for therapeutic trials. Neurology 66: 228-232, 2006. The clinical course in Type A Niemann-Pick disease is similar among affected patients and is characterized by a relentless neurodegenerative course that leads to death, usually within 3 years.
High sphingomyelin levels induce lysosomal damage and autophagy dysfunction in Niemann Pick disease type A. Niemann Pick disease type A (NPA), which is caused by loss of function mutations in the acid sphingomyelinase (ASM) gene, is a lysosomal storage disorder leading to neurodegeneration. Undegraded molecules build up in neurons of acid sphingomyelinase knockout mice and in fibroblasts from NPA patients in which autophagolysosomes accumulate. The latter is not due to alterations in autophagy initiation or autophagosome-lysosome fusion but because of inefficient autophago-lysosomal clearance. T his, in turn, can be explained by lysosomal membrane permeabilization leading to cytosolic release of Cathepsin B. High sphingomyelin (SM) levels account for these effects as they can be induced in control cells on addition of the lipid and reverted on SM-lowering strategies in ASM-deficient cells. These results unveil a relevant role for SM in autophagy modulation and characterize autophagy anomalies in NPA, opening new perspectives for therapeutic interventions.
Niemann-Pick disease type A usually develop an enlarged liver and spleen (hepatosplenomegaly) by age 3 months and fail to gain weight and grow at the expected rate (failure to thrive). The affected children develop normally until around age 1 year when they experience a progressive loss of mental abilities and movement (psychomotor regression). Children with Niemann-Pick disease type A also develop widespread lung damage (interstitial lung disease) that can cause recurrent lung infections and eventually lead to respiratory failure. All affected children have an eye abnormality called a cherry-red spot, which can be identified with an eye examination. Children with Niemann-Pick disease type A generally do not survive past early childhood.
The totality of all processes through which the Niemann–Pick disease type B is realized. This causal process is heredity.
Kirkegaard et al. (2010) showed that Hsp70 (140550) stabilizes lysosomes by binding to an endolysosomal anionic phospholipid bis(monoacylglycero)phosphate (BMP), an essential cofactor for lysosomal sphingomyelin metabolism. In acidic environments Hsp70 binds with high affinity and specificity to BMP, thereby facilitating the BMP binding and activity of acid sphingomyelinase (ASM). The inhibition of the Hsp70-BMP interaction by BMP antibodies or a point mutation in Hsp70 (trp90 to phe), as well as the pharmacologic and genetic inhibition of ASM, effectively reverted the Hsp70-mediated stabilization of lysosomes. Notably, the reduced ASM activity in cells from patients with Niemann-Pick disease A (257200) and B, severe lysosomal storage disorders caused by mutations in the sphingomyelin phosphodiesterase-1 gene (SMPD1; 607616) encoding ASM, is also associated with a marked decrease in lysosomal stability, and this phenotype could be effectively corrected by treatment with recombinant Hsp70. Kirkegaard et al. (2010) concluded that, taken together, their data opened exciting possibilities for the development of new treatments for lysosomal storage disorders and cancer with compounds that enter the lysosomal lumen by the endocytic delivery pathway. https://omim.org/entry/607616 Hsp70 stabilizes lysosomes and reverts Niemann-Pick disease-associated lysosomal pathology. Nature 463: 549-553, 2010. [
Niemann-Pick disease type B usually presents in mid-childhood. The signs and symptoms of this type are similar to type A, but not as severe. People with Niemann-Pick disease type B often have hepatosplenomegaly, recurrent lung infections, and a low number of platelets in the blood (thrombocytopenia). They also have short stature and slowed mineralization of bone (delayed bone age). About one-third of affected individuals have the cherry-red spot eye abnormality or neurological impairment. People with Niemann-Pick disease type B usually survive into adulthood.
Retinal degeneration is a subtype of changing material: A process that degenerates retinal photoreceptors and pigmented epithelial cells.
Detinal degenration is usually caused by the progressive cell death.
Retinal degeneration is a subtype of changing material: A process that degenerates retinal photoreceptors and pigmented epithelial cells. This entity is a specific course-dependent process. This process can constitute the course of Niemann-Pick Disease Type A.
retinal degeneration [Niemann Pick Disease Type A]
Dysfunction of sphingomyelin degradation in the myelin sheath is a subtype of dysfunction of phosphosphingolipid degradation: A process that performs an abnormal and incomplete sphingomyelin degradation in the myelin sheath. This entity is a specific course-dependent process. This process can constitute the course of Niemann Pick Disease Type A.
dysfunction of sphingomyelin degradation in the myelin sheath [Niemann Pick Disease Type A]
Dysfunction of sphingomyelin degradation in the myelin sheath is a subtype of dysfunction of phosphosphingolipid degradation: A process that performs an abnormal and incomplete sphingomyelin degradation in the myelin sheath.
dysfunction of sphingomyelin degradation in the myelin sheath
Dysfunction of phosphosphingolipid degradation is a subtype of dysfunction of phospholipid degradation: A process that performs an abnormal and incomplete phosphosphingolipid degradation.
dysfunction of phosphosphingolipid degradation
Dysfunction of sphingomyelin degradation is a subtype of dysfunction of phosphosphingolipid degradation: A process that performs an abnormal and incomplete sphingomyelin degradation. This entity is a specific course-dependent process. This process can constitute the course of Niemann Pick Disease Type A/ B.
dysfunction of sphingomyelin degradation [Niemann Pick Disease Type A/ B]
A process that becomes lacking a homeostastasis balance of the sphingomyelin metabolism. This entity is a specific course-dependent process. This process can constitute the course of Niemann Pick Disease Type A/ B.
sphingomyelin metabolism imbalance [Niemann Pick Disease Type A/ B]
Pulmonary infection is a subtype of pathogen colonization: A process that makes pathogen such as microorganism (bacteria, virus, mycoplasma, etc.) present in the lung to increase the number.
Pulmonary infection is a subtype of pathogen colonization: A process that makes pathogen such as microorganism (bacteria, virus, mycoplasma, etc.) present in the lung to increase the number. This entity is a specific course-dependent process. This process can constitute the course of Niemann Pick Disease Type A/ B.
pulmonary infection [Niemann Pick Disease Type A/ B]
Decrease in platelet count is a subtype of decreasing number of objects: A process that becomes smaller in platelet count.
Decrease in platelet count is a subtype of decreasing number of objects: A process that becomes smaller in platelet count. This entity is a specific course-dependent process. This process can constitute the course of Niemann-Pick Disease Type B.
decrease in platelet count [Niemann Pick Disease Type B]
Pulmonary infection is a subtype of pathogen colonization: A process that makes pathogen such as microorganism (bacteria, virus, mycoplasma, etc.) present in the lung to increase the number. This entity is a specific course-dependent process. This process can constitute the course of Niemann Pick Disease Type A.
pulmonary infection [Niemann Pick Disease Type A]
A process that becomes lacking a homeostastasis balance of the sphingomyelin metabolism. This entity is a specific course-dependent process. This process can constitute the course of Niemann Pick Disease Type A.
sphingomyelin metabolism imbalance [Niemann Pick Disease Type A]
Hyperfunction of phospholipid removing is a subtype of hyperfunctioning: A process that performs an excessive removal of phospholipids.
Hyperfunction of phospholipid removing is a subtype of hyperfunctioning: A process that performs an excessive removal of phospholipids. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense).
hyperfunction of phospholipid removing [Phospholipidosis (excessive defense)]
lysophagy is a subtype of autophagy: A process that becomes larger in the number of autodigestion of abnormal lysosome. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense) .
lysophagy [Phospholipidosis (excessive defense) ]
Hyperfunction of immune response is a subtype of hyperfunctioning: A process that performs an excessive immune response.
Hyperfunction of immune response is a subtype of hyperfunctioning: A process that performs an excessive immune response. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense).
hyperfunction of immune response [Phospholipidosis (excessive defense)]
Inflammatory response is a subtype of changing material: The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense).
iflammation [Phospholipidosis (excessive defense)]
inflammatory response [Phospholipidosis (excessive defense)]
Any process that modulates the rate or extent of progression through the cell cycle. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense) .
regulation of cell cycle [Phospholipidosis (excessive defense) ]
The multiplication or reproduction of cells, resulting in the rapid expansion of a cell population. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense) .
cell proliferation [Phospholipidosis (excessive defense) ]
Tumor cell proliferation is a subtype of cell proliferation: A process of the multiplication or reproduction of tumor cells, resulting in the rapid expansion of a tumor cell population. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense) .
tumor cell proliferation [Phospholipidosis (excessive defense) ]
EGFR signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal transmitted by the EGFR (epidermal growth factor receptor) on the surface of a cell, starting with a ligand binding to a EGFR
EGFR signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal transmitted by the EGFR (epidermal growth factor receptor) on the surface of a cell, starting with a ligand binding to a EGFR This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense) .
EGFR signaling (primitive) [Phospholipidosis (excessive defense) ]
AKT signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal transmitted by the intracellular serine/threonine kinase protein kinase B (also called AKT).
Phosphatidylinositol 3-kinase signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal transmitted by the phosphatidylinositol 3-kinase (PI3K). This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense) .
phosphatidylinositol 3-kinase signaling (primitive) [Phospholipidosis (excessive defense) ]
Moving free fatty acid to the hepatocyte is a subtype of moving A to the inside of B: A process of the movement of free fatty acid into a hepatocyte. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
moving free fatty acid to the hepatocyte [eosinogranular degeneration]
The spread or migration of cancer cells from one part of the body (the organ in which it first appeared) to another. The secondary tumor contains cells that are like those in the original (primary) tumor. [def-source: NCI] This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense).
metastasis [Phospholipidosis (excessive defense)]
A role played by the molecule which transfers free fatty acids.
Hyperfunction of uptaking fatty acid into liver is a a process that performs an excesssive uptaking of fatty acids into the iver. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
hyperfunction of uptaking fatty acid [lipidosis]
Hyperfunction of uptaking fatty acid into liver is a a process that performs an excesssive uptaking of fatty acids into the iver.
Finding is a subtype of data item that the result (output) of an investigation or an image finding, or some combination thereof.
monomeric FXR imight represss human SLCO2B1
Changing time length is a subtype of changing quality: A process that changes the length of time.
ATP-BINDING cassette (ABC) transporter superfamily (canonical)[Cholestasis]
A pathological finding is a subtype of finding, which is observed as the lesion based on the pathological morphology.
myelin figure [Liver PathologicalFindings] is a type of finding observed in the liver. Based on pathological morphology, lesions are observed as myelin-like layered structures under electron microscopy.
myeloid body [Liver PathologicalFindings]
myelin figure [Liver Pathological Findings]
An attribute value of a tumor. This entity is a subtype of categorical value, which is non-quantitative and is dependent on tumors.
A value of the attribute of tumors that progress, invade surrounding tissues or metastasize.
An attribute value of a tumor that does not progress, not invade surrounding tissues or not metastasize.
Signal integration system is a subtype of pathway system. This entity has sub-parts and has a goal of transmitting signals and a gene regulation as a systemic context.
Catalysis role of the transfer of a phosphate group, usually from ATP, to a substrate molecule.
Negative regulation ofglycosylation is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of glycosylation.
sequestering of triglyceride (mild) is a subtype of lipid strorage in hepatocyte: A process that keeps triglycerides in hepatocytes. And the degree is mild. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
sequestering of triglyceride in hepatocyte (mild) [lipidosis]
Changing pH is a subtype of changing quality: A process that changes the pH of the object, which denotes the acidity of a solution in terms of activity of hydrogen ions (H+).
sequestering of triglyceride (moderate) is a subtype of lipid strorage in hepatocyte: A process that keeps triglycerides in hepatocytes. And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
sequestering of triglyceride in hepatocyte (moderate) [lipidosis]
sequestering of triglyceride in hepatocyte is a subtype of lipid strorage in hepatocyte: A process that keeps triglycerides in hepatocytes. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
sequestering of triglyceride in hepatocyte
Any process that modulates the frequency, rate or extent of the innate immune response, the organism's first line of defense against infection. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
regulation of innate immune response [Phospholipidosis]
A physical attribute inhering in a bearer by virtue of the bearer's rate of change of the position
A lymphocyte that can spontaneously kill a variety of target cells without prior antigenic activation via germline encoded activation receptors and also regulate immune responses via cytokine release and direct contact with other cells.
lymphocyte and (capable of some natural killer cell mediated immunity) and (capable of some regulation of immune response) and (lacks_plasma_membrane_part some CD19 molecule) and (lacks_plasma_membrane_part some CD3 epsilon) and (lacks_plasma_membrane_part some membrane-spanning 4-domains subfamily A member 1) and (lacks_plasma_membrane_part some CD14 molecule)
JNK activation by IRE1 is a subtype of JNK activation: A process that changes the activity of the JNK to be higher by IRE1.
PERK signal integration system is a subtype of pathway system. This entity has sub-parts and has a goal of transmitting signals and a gene regulation via PERK as a systemic context.
JNK activation by IRE1 is a subtype of JNK activation: A process that changes the activity of the JNK to be higher by IRE1. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
A role that represses the rate, timing and/or magnitude of transcription of genetic information.
Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the trans-Golgi network (TGN) and endosomes. The AP complexes mediate the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules.
Adaptor Related Protein Complex 1 Mu 2 Subunit [Phospholipidosis]
Phosphatidylinositol 4 phosphate regulates targeting of clathrin adaptor AP-1 complexes to the Golgi. Cell, 114, 299-310 (2003)
Type I gamma phosphatidylinositol phosphate kinase modulates adherens junction and E-cadherin trafficking via a direct interaction with mu 1B adaptin: Type Igamma phosphatidylinositol phosphate kinase (PIPKIgamma) directly binds to E-cadherin and modulates E-cadherin trafficking. PIPKIgamma also interacts with the mu subunits of clathrin adaptor protein (AP) complexes and acts as a signalling scaffold that links AP complexes to E-cadherin. PIPKIgamma serves as both a scaffold, which links E-cadherin to AP complexes and the trafficking machinery, and a regulator of trafficking events via the spatial generation of phosphatidylinositol-4,5-bisphosphate.
The cytosolic adaptor AP-1A is essential for the trafficking and function of Niemann-Pick type C proteins.
PERK-eIF2a-ATF4 signal integration system is a subtype of PERK pathway system. This entity has sub-parts and has a goal of transmitting signals and a gene regulation via PERK, eIF2a, and ATF4 as a systemic context.
PERK-eIF2a-ATF4 signal integration system
Sorting cargo transport signal is a subtype of extractng: A process that obtains a necessary cargo transport signal.
The totality of all processes through which the Niemann–Pick disease type C is realized. This causal process is heredity.
NPC1 is involved in sphingosine efflux from lysosomes, and that lysosomal sphingosine accumulation in NPC alters intracellular calcium concentration and causes abnormal endocytic trafficking Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium. Nature Med. 14: 1247-1255, 2008.
Murine model of Niemann-Pick C disease: mutation in a cholesterol homeostasis gene. Science 277: 232-235, 1997.
Mutations in either the NPC1 or NPC2 gene cause Niemann-Pick disease type C. The proteins produced from these genes are involved in the movement of lipids within cells. Mutations in these genes lead to a shortage of functional protein, which prevents movement of cholesterol and other lipids, leading to their accumulation in cells. Because these lipids are not in their proper location in cells, many normal cell functions that require lipids (such as cell membrane formation) are impaired. The accumulation of lipids as well as the cell dysfunction eventually leads to cell death, causing the tissue and organ damage seen in Niemann-Pick disease types C1 and C2.
An attribute in which events occur in sequence.
Lysosomal cholesterol storage is a subtype of cholesterol storage: A process that keeps cholesterol in the lysosome.
Lysosomal cholesterol storage is a subtype of cholesterol storage: A process that keeps cholesterol in the lysosome. This entity is a specific course-dependent process. This process can constitute the course of Niemann-Pick Disease Type C.
lysosomal cholesterol storage [Niemann Pick Disease Type C]
Dysfunction of mitochondrial fatty acid beta-oxidation (severe) is a subtype of hypofunction of fatty acid beta-oxidation: A process that performs a decreased or insufficient fatty acid beta-oxidation severely. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
Dysfunction of mitochondrial fatty acid beta-oxidation (severe) [Lipidosis]
Hypofunction of ATP biosynthesis is a subtype of hypofunction of biosynthesis: A process that performs a decreased or insufficient ATP biosynthesis. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
hypofunction of ATP biosynthesis [lipidosis]
Overeating is a subtype of increasing quantity: A process that changes the ingestion amount of food to be larger.
A behavioral process associated with the intake of food. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
feeding behavior [Phospholipidosis (severe) ]
CAR -cell senescence inhibitor (canonical)[Ground glass appearance]
Catalysis role of the reaction: anandamide + H2O <=> arachidonate + ethanolaminium(1+)
Hypofunction of phosphoethanolamine degradation is a subtype of hypofunction of decomposing: A process that performs a decreased or insufficient phosphoethanolamine degradation.
Decreasing phosphoethanolamine degradation is a subtype of decreasing functioning process of breakdown of phosphoethanolamine.
hypofunction of phosphoethanolamine degradation
Regulation of hepatocyte cell cycle is a subtype of regulation of cell cycle: A process that modulates the frequency, rate or extent of hepatocyte cell cycle. This entity is a specific course-dependent process. This process can constitute the course of Hypertrophy.
regulation of hepatocyte cell cycle [Hypertrophy]
P53 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by p53. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense) .
p53 signaling (primitive) [Phospholipidosis (excessive defense) ]
Catalysis role of the reaction: erythro-5-hydroxy-L-lysine + GTP = 5-phosphonooxy-L-lysine + GDP + 2 H(+)
Molecular identification of hydroxylysine kinase and of ammoniophospholyases acting on 5-phosphohydroxy-L-lysine and phosphoethanolamine. J. Biol. Chem. 287: 7246-7255, 2012. [
A. Identification and functional characterization of new potentially defective alleles of human CYP2C19. Pharmacogenetics 12: 703-711, 2002. [
Hepatic cytochrome P450 enzyme alterations in humans with progressive stages of nonalcoholic fatty liver disease. Microsomal protein expression of CYP1A2, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 tended to decrease with NAFLD progression. Functional activity assays revealed decreasing trends in CYP1A2 (p = 0.001) and CYP2C19 (p = 0.05) enzymatic activity with increasing NAFLD severity. Increased expression of proinflammatory cytokines tumor necrosis factor alpha and interleukin 1beta was observed and may be responsible for observed decreases in respective P450 activity.
Aminoglycoside-induced suppression of CYP2C19*3 premature stop codon.
The action of cytochrome b(5) on CYP2E1 and CYP2C19 activities requires anionic residues D58 and D65.
Hypofunction of drug metabolism phase I is a subtype of hypofunction of drug metabolism: A process that performs a decreased or insufficient drug metabolism phase I.
Hyperfunction of drug metabolism phase I is a subtype of hyperfunction of drug metabolism: A process that performs an excesssive drug metabolism phase I. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
hyperfunction of drug metabolism phase I [Phospholipidosis]
Hypofunction of cholesterol transport from lysosome is a subtype of hypofunction of transport: A process that performs a decreased or insufficient cholestsrol transport from lysosomes. This entity is a specific course-dependent process. This process can constitute the course of Niemann-Pick type C.
hypofunction of cholesterol transport in lysosome [Niemann-Pick type C] .
Cholesteroltransport gene mutation is a subtype of gene mutation: A process thatchanges the sequence of a cholesterol transport gene. This process is dependent on the genetic and can constitute the course of Niemann Pick Type C.
cholesterol transport gene mutation [Niemann Pick Type C]
AAPS J. 2006 Mar 10;8(1):E101-11. Cytochrome P450s and other enzymes in drug metabolism and toxicity.
Drug metabolism phase I by Cytochrome P450 is a subtype of drug metabolism phase I: A process that is biotransformed by cytochrome P450 (CYP) superfamily .
drug metabolism phase I by Cytochrome P450
Induction of apoptosis by cationic amphiphilic drugs amiodarone and imipramine. These observations suggested that accumulation of cellular phospholipids could inhibit cell proliferation. Amiodarone and imipramine induced apoptosis in U-937 cells and induced the activity of caspases 2 and 3. These results suggest that disruption of cell lysosomes in U-937 cells following accumulation of phospholipids does not cause a cell cycle arrest but instead induces apoptosis by activation of caspase pathways.
A role played by the entity to repair the damaged DNA.
Xenobiotica. 1999 Feb;29(2):187-93. Contribution of human hepatic cytochrome P450s and steroidogenic CYP17 to the N-demethylation of aminopyrine. Among the hepatic P450s, the N-demethylation of aminopyrine was catalysed most efficiently by CYP2C19, followed by CYP2C8, 2D6, 2C18 and 1A2, whereas the activity with CYP2E1 was negligible.
Biol Pharm Bull. 2000 Apr;23(4):498-501. Inhibition of drug-metabolizing enzyme activity in human hepatic cytochrome P450s by bisphenol A. CYP2C19 and CYP2B6 catalyzed most efficiently the aminopyrine N-demethylation, followed by CYP2C8 and CYP2D6. Bisphenol A (1 mM) most efficiently inhibited aminopyrine N-demethylation by CYP2C8 and CYP2C19 by 82% and 85%, respectively, whereas inhibition of the activities by CYP 2B6 and 2D6 was less than 40%. Bisphenol A inhibits CYP2C19-mediated S-mephenytoin 4-hydroxylation.
Acta Pharm Sin B. 2016 Sep; 6(5): 413–425. Insights into CYP2B6-mediated drug–drug interactions
Amitriptyline metabolism is a subtype of drug metabolism phase I by Cytochrome P450: A process that that is biotransformed of amitriptyline by cytochrome P450 (CYP) superfamily (CYP2D6, CYP1A2, and CYP2C9. ) This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
amitriptyline metabolism [Phospholipidosis]
Amitriptyline metabolism is a subtype of drug metabolism phase I by Cytochrome P450: A process that that is biotransformed of amitriptyline by cytochrome P450 (CYP) superfamily (CYP2D6, CYP1A2, and CYP2C9. )
A length quality value which is greater than the normal or average.
P450-Based Drug-Drug Interactions of Amiodarone and its Metabolites: Diversity of Inhibitory Mechanisms.: Both AMIO and its metabolites MDEA appear to be important in DDIs resulting from inhibition of CYP2D6.
The Use of In Vitro Data and Physiologically-Based Pharmacokinetic Modeling to Predict Drug Metabolite Exposure: Desipramine Exposure in Cytochrome P4502D6 Extensive and Poor Metabolizers Following Administration of Imipramine.
Decreasing ceramide is a subtype of decreasing lipid: A process that changes the quantity of the ceramide to be lower. This entity is a specific course-dependent process. This process can constitute the course of sphingomyelin disorder.
decreasing ceramide [sphingomyelin disorder ]
Hepatocyte cell division is a subtype of cell division: The process resulting in division and partitioning of components of a heoatocyte cell to form more cells.
PPARalpha inactivation is a subtype of inactivating: A process that changes the activity of the activating PPAR alpha ( (Peroxisome Proliferator Activated Receptor Alpha)) with a nuclear receptor role to be lower.
inactivating peroxisome proliferator-activated receptor alpha
PERK-eIF2a-ATF4 signal integration system signal integration system is a subtype of PERK pathway system. This entity has sub-parts and has a goal of transmitting signals and a gene regulation via PERK, eIF2a, ATF4, and CHOP as a systemic context.
PERK-eIF2a-ATF4-CHOP signal integration system
Glycerophospholipid metabolism balance is a subtype of phospholipid metabolism balance: A process that keeps a balance of glycerophospholipid metabolism.
Glycerophospholipid metabolism balance is a subtype of phospholipid metabolism balance: A process that keeps a balance of glycerophospholipid metabolism. This process is dependent on the glycerophospholipid disorder and can constitute the course of Phospholipidosis.
glycerophospholipid metabolism balance [phospholipidosis - glycerophospholipid disorder]
Heoatocyte growth is a subtype of cell growth: A process that The process in which a hepatocyte, the main structural component of the liver, increases in size.
Phosphatidylcholine metabolism balance is a subtype of glycerophospholipid metabolism balance: A process that keeps a balance of phosphatidylcholine metabolism.
Regulation of hepatocyte cell cycle [hypertrophy] is a subtype of regulation of cell cycle: A process that modulates the frequency, rate or extent of hepatocyte cell cycle.
Stagnating is a subtype of decreasing velocity: A process that changes the flow velocity to be slower or stops it in progress.
Increasing distance between hepatocytes is a subtype of increasing distance between cells: A process that places a distance between hepatocytes. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
separating between hepatocytes [Ground glass appearance]
increasing distance between hepatocytes [Ground glass appearance]
Increasing phosphatidylcholine material is a subtype of increasing glycerophospholipid material: A process that changes the amount of phosphatidylcholine material to be larger.
The chemical reactions and pathways involving a drug, a substance used in the diagnosis, treatment or prevention of a disease; as used here antibiotic substances (see antibiotic metabolism) are considered to be drugs, even if not used in medical or veterinary practice. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
drug metabolic process [Ground glass appearance]
Phosphatidylcholine metabolism imbalance is a subtype of glycerophospholipid metabolism imbalance : A process that becomes lacking a homeostastasis balance of phosphatidylcholine metabolism.
phosphatidylcholine metabolism imbalance
Sgpl1 - apoptosis inducer (mouse)[Phospholipidosis]
Hyperfunction of Phosphatidylcholine synthesis gene expression is a subtype of hyperfunction of glycerophospholipid synthesis gene expression: A process that performs an excesssive phosphatidylcholine ssynthetic gene expression.
hyperfunction of Phosphatidylcholine synthesis gene expression
The totality of all processes through which ground glass appearance is realized. This toxic course has a process of Cytochrome P450 (CYP) activation by phenobarbital.
ground glass appearance with Cytochrome P450 activation by phenobarbital
Nuclear receptor inactivation is a subtype of inactivation : A process that changes the activity of the molecule with a nuclear receptor role to be lower.
Increasing distance between hepatocytes is a subtype of increasing distance between cells: A process that places a distance between hepatocytes.
Drug metabolism phase II is a subtype of drug metabolic process: A process that of biotransformation reactions involving conjugate enabling efficient excretion.
Increasing phosphatidylethanolamine material is a subtype of increasing glycerophospholipid material: A process that changes the amount of phosphatidylethanolamine material to be larger.
increasing phosphatidylethanolamine material
Drug metabolism phase II is a subtype of drug metabolic process: A process that of biotransformation reactions involving conjugate enabling efficient excretion. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
drug metabolism phase II [Ground glass appearance]
Phosphatidylethanolamine metabolism imbalance is a subtype of glycerophospholipid metabolism imbalance : A process that becomes lacking a homeostastasis balance of phosphatidylethanolamine metabolism.
phosphatidylethanolamine metabolism imbalance
Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (sphingomyelin disorder) .
negative regulation of apoptotic process [Phospholipidosis-sphingomyelin disorder]
Hyperfunctioning of phosphatidylethanolamine synthesis gene expression is a subtype of hyperfunction of glycerophospholipid synthesis gene expression: A process that performs an excesssive phosphatidylethanolamine synthetic gene expression.
hyperfunctioning of phosphatidylethanolamine synthesis gene expression
Drug metabolism phase I is a subtype of drug metabolic process: A process that of biotransformation reactions involving hydrolysis, reduction, and oxidation or introduces a functional group (such as -OH, -NH2, -SH or -COOH) to increase in the water solubility of a xenobiotic. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
drug metabolism phase I [Ground glass appearance]
Negative regulation of phosphatidylethanolamine degradation is a subtype of Negative regulation of glycerophospholipid degradation: A process that stops, prevents, or reduces the frequency, rate or extent of phosphatidylethanolamine degradation.
negative regulation of phosphatidylethanolamine degradation
The modification of a xenobiotic substance by the conjugation of glucuronic acid. The resultant glucuronosides are often much more water-soluble than the xenobiotic precursor, enabling efficient excretion. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
In the liver, bilirubin is conjugated with glucuronic acid by the enzyme glucuronyltransferase, making it soluble in water: the conjugated version is the main form of bilirubin present in the "direct" bilirubin fraction. Much of it goes into the bile and thus out into the small intestine.
UGT1A1 responsible for conjugating bilirubin is inducible by CAR activators such as phenobarbital and scoparone.
xenobiotic glucuronidation [Ground glass appearance]
Hyperfunction of phosphatidylinositol biosynthesis is a subtype of hyperfunction of glycerophospholipid biosynthesis: A process that performs an excessive phosphatidylinositol biosynthesis.
hyperfunction of phosphatidylinositol biosynthesis
Hyperfunction of phosphatidylethanolamine biosynthesis is a subtype of hyperfunction of glycerophospholipid biosynthesis: A process that performs an excessive phosphatidylethanolamine biosynthesis.
hyperfunction of phosphatidylethanolamine biosynthesis
Hyperfunction of phosphatidylglycerol biosynthesis is a subtype of hyperfunction of glycerophospholipid biosynthesis: A process that performs an excessive phosphatidylglycerol biosynthesis.
hyperfunction of phosphatidylglycerol biosynthesis
Hyperfunction of phosphatidylcholine biosynthesis is a subtype of hyperfunction of glycerophospholipid biosynthesis: A process that performs an excessive phosphatidylcholine biosynthesis.
hyperfunction of phosphatidylcholine biosynthesis
Hyperfunction of phosphatidyl-L-serine biosynthesis is a subtype of hyperfunction of glycerophospholipid biosynthesis: A process that performs an excessive phosphatidyl-L-serine biosynthesis.
hyperfunction of phosphatidyl-L-serine biosynthesis
Glutathione conjugation is a subtype of drug metabolism phase II: Glutathione conjugation is a detoxication reaction. Four types of activation reaction have been recognized: direct-acting compounds, conjugates that are activated through cysteine conjugate beta-lyase, conjugates that are activated through redox cycling and lastly conjugates that release the original reactive parent compound. The glutathione S-transferases have three connections with the formation of biactivated conjugatesto make them more soluble for excretion. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
glutathione conjugation [Ground glass appearance]
Increasing phosphatidylglycerol material is a subtype of increasing glycerophospholipid material: A process that changes the amount of phosphatidylglycerol material to be larger.
increasing phosphatidylglycerol material
Gene expression of cytochrome p450 is a subtype of gene expression: The process in which a gene sequence is converted into a mature cytochrome p450 gene product or products (proteins or RNA) . This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
gene expression of cytochrome p450 [Ground glass appearance]
Phosphatidylglycerol metabolism imbalance is a subtype of glycerophospholipid metabolism imbalance : A process that becomes lacking a homeostastasis balance of phosphatidylglycerol metabolism.
phosphatidylglycerol metabolism imbalance
S1P -apoptosis inhibitor (inactivated state)[Phospholipidosis - positive regulation of apoptosis]
Hypofunction of phosphatidylglycerol degradation is a subtype of hypofunction of glycerophospholipid degradation: A process that performs a decreased or insufficient phosphatidylglycerol degradation.
hypofunction of phosphatidylglycerol degradation
Gene expression of cytochrome p450 is a subtype of gene expression: The process in which a gene sequence is converted into a mature cytochrome p450 gene product or products (proteins or RNA) .
Hyperfunction of phosphatidylglycerol synthesis gene expression is a subtype of hyperfunction of glycerophospholipid synthesis gene expression: A process that performs an excesssive phosphatidylglycerol synthetic gene expression.
hyperfunction of phosphatidylglycerol synthesis gene expression
Smooth endoplasmic reticulum membrane organization is a subtype of endoplasmic reticulum membrane organization: A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts of a smooth endoplasmic reticulum membrane. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
smooth endoplasmic reticulum membrane organization [Ground glass appearance]
Negative regulation of phosphatidylglycerol degradation is a subtype of Negative regulation of glycerophospholipid degradation: A process that stops, prevents, or reduces the frequency, rate or extent of phosphatidylglycerol degradation.
negative regulation of phosphatidylglycerol degradation
Smooth endoplasmic reticulum membrane organization is a subtype of endoplasmic reticulum membrane organization: A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts of a smooth endoplasmic reticulum membrane.
smooth endoplasmic reticulum membrane organization
Changing color is a subtype of changing quality: A process that chnges the color of the object.
Increasing distance between cells is a subtype of increasing distance: A process that places a distance between cells.
PPARalpha inactivation is a subtype of inactivation: A process that changes the activity of the activating PPAR alpha (Peroxisome Proliferator Activated Receptor Alpha) with a nuclear receptor role to be lower. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
Reactome The set of genes regulated by PPAR-alpha is not fully known in humans, however many examples have been found in mice. Genes directly activated by PPAR-alpha contain peroxisome proliferator receptor elements (PPREs) in their promoters and include: 1) genes involved in fatty acid oxidation and ketogenesis (Acox1, Cyp4a, Acadm, Hmgcs2); 2) genes involved in fatty acid transport (Cd36, , Slc27a1, Fabp1, Cpt1a, Cpt2); 3) genes involved in producing fatty acids and very low density lipoproteins (Me1, Scd1); 4) genes encoding apolipoproteins (Apoa1, Apoa2, Apoa5); 5) genes involved in triglyceride clearance ( Angptl4); 6) genes involved in glycerol metabolism (Gpd1 in mouse);
Liver PPARα expression negatively correlated with the presence of NASH (p=0.001) and with severity of steatosis (p=0.003), ballooning (p=0.001), NASH activity score (p=0.008) and fibrosis (p=0.003).
Any process that modulates the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of precursor metabolites, substances from which energy is derived, and the processes involved in the liberation of energy from these substances. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
regulation of generation of precursor metabolites and energy [Ground glass appearance]
Phosphatidic acid degradation is a subtype of glycerophospholipid catabolic process: A process of the chemical reactions resulting in the breakdown of phosphatidic acid.
Hyperfunction of drug metabolism phase I by Cytochrome P450 is a subtype of hyperfunction of drug metabolism phase I: A process that performs an excesssive drug metabolism phase I by Cytochrome P450. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
hyperfunction of drug metabolism phase I by Cytochrome P450 [Ground glass appearance]
Hyperfunction of phosphatidic acid biosynthesis is a subtype of hyperfunction of glycerophospholipid biosynthesis: A process that performs an excessive phosphatidic acid biosynthesis.
hyperfunction of phosphatidic acid biosynthesis
Hyperfunction of drug metabolism phase I by Cytochrome P450 is a subtype of hyperfunction of drug metabolism phase I: A process that performs an excesssive drug metabolism phase I by Cytochrome P450.
hyperfunction of drug metabolism phase I by Cytochrome P450
Hyperfunction of phosphosphingolipid biosynthesis is a subtype of hyperfunction of phospholipid biosynthesis: A process that performs an excessive phosphosphingolipid biosynthesis.
hyperfunction of phosphosphingolipid biosynthesis
Hyperfunction of sphingomyelin biosynthesis is a subtype of hyperfunction of phosphosphingolipid biosynthesis: A process that performs an excessive sphingomyelin biosynthesis.
hyperfunction of sphingomyelin biosynthesis
ER stress response gene expression via PERK is a subtype of gene expression: The process in which a gene sequence is converted into a mature ER stress response gene product or products (proteins or RNA) by PERK.
ER stress response gene expression via PERK
Hyperfunction of cytochrome p450 gene expression is a subtype of hyperfunction of drug metabolizing enzyme gene expression: A process that performs an excesssive gene expression of cytochrome p450. This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (sustained) .
hyperfunction of cytochrome p450 gene expression by phenobarbital (sustained) [Ground glass appearance]
Increasing phosphatidic acid material is a subtype of increasing glycerophospholipid material: A process that changes the amount of phosphatidic acid material to be larger.
Hyperfunction of drug metabolism phase I by Cytochrome P450 is a subtype of hyperfunction of drug metabolism phase I: A process that performs an excesssive drug metabolism phase I by Cytochrome P450. This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (sustained) .
hyperfunction of drug metabolism phase I by Cytochrome P450 (sustained) [Ground glass appearance]
Increasing phosphatidylserine material is a subtype of increasing glycerophospholipid material: A process that changes the amount of phosphatidylserine material to be larger.
Increasing amount of foreign substance is a subtype of increasing quantity: A process that changes the amount of foreign substance to be higher.
Peroxisome Proliferator-Activated Receptor Alpha [lipidosis]
Increasing amount of xenobiotics is a subtype of increasing amount of foreign substance: A process that changes the amount of xenobiotics to be higher.
Increasing amount of drug is a subtype of increasing amount of xenobiotics: A process that changes the amount of drug to be higher.
AMPK inactivation is a subtype of molecular inactivation: A process that changes the activity of the AMPK (AMP-activated protein kinase) to be lower.
Increasing amount of drug is a subtype of increasing amount of xenobiotics: A process that changes the amount of drug to be higher. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
increasing amount of drug [Ground glass appearance]
AMPK inactivation is a subtype of molecular inactivation: A process that changes the activity of the AMPK (AMP-activated protein kinase) to be lower. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
AMPK is sensitive to energy charge, which is activated by an increase in the ratio of AMP/ATP.
When ethanol is added to cultured hepatoma cells that oxidize ethanol, it induces transcription of an SREBP-regulated promoter and increases the levels of the mature form of SREBP-1. AMPK regulates the ethanol-elicited SREBP-1 activation and the development of steatosis.
Decreasing amount of drug is a subtype of decreasing amount of xenobiotics: A process that changes the quantity of the drug to be lower.
Phosphatidylserine metabolism imbalance is a subtype of glycerophospholipid metabolism imbalance : A process that becomes lacking a homeostastasis balance of phosphatidylserine metabolism.
Removing myelin figure by Kupffer cell or macrophage is a subtype of removing: A process that takes myelin figure from a cell by Kupffer cells or macrophages.
removing myelin figure by Kupffer cell or macrophage
Phosphatidic acid metabolism imbalance is a subtype of glycerophospholipid metabolism imbalance : A process that becomes lacking a homeostastasis balance of phosphatidic acid metabolism.
Removing myelin figure by Kupffer cell or macrophage is a subtype of removing: A process that takes myelin figure from a cell by Kupffer cells or macrophages. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
removing myelin figure by Kupffer cell or macrophage [Phospholipidosis]
Phosphatidylinositol metabolism imbalance is a subtype of glycerophospholipid metabolism imbalance : A process that becomes lacking a homeostastasis balance of phosphatidylinositol metabolism.
phosphatidylinositol metabolism imbalance
Lipid accumulation in hepatocyte is a subtype of lipid strorage in hepatocyte: A process that keeps lipids in hepatocytes mildly. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
lipid accumulation in hepatocyte [Phospholipidosis]
Hyperfunction of Phosphatidylserine synthesis gene expression is a subtype of hyperfunction of glycerophospholipid synthesis gene expression: A process that performs an excesssive phosphatidylserine synthetic gene expression.
hyperfunction of Phosphatidylserine synthesis gene expression
Decreasing amount of drug is a subtype of decreasing amount of xenobiotics: A process that changes the quantity of the drug to be lower. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
decreasing amount of drug [Ground glass appearance]
Hypofunction of phosphatidylserine degradation is a subtype of hypofunction of glycerophospholipid degradation: A process that performs a decreased or insufficient phosphatidylcholine degradation.
hypofunction of phosphatidylserine degradation
Keeping amount of drug is a subtype of keeping amount: A process that maintains the amount of the drug at a constant level .
Negative regulation of phosphatidylserine degradation is a subtype of Negative regulation of glycerophospholipid degradation: A process that stops, prevents, or reduces the frequency, rate or extent of phosphatidylserine degradation.
negative regulation of phosphatidylserine degradation
Cell rupture is the tearing apart of a cell.
Increasing phosphatidylinositol material is a subtype of increasing glycerophospholipid material: A process that changes the amount of phosphatidylinositol material to be larger.
increasing phosphatidylinositol material
Hyperfunction of decreasing the amount of phenobarbital is a subtype of hyperfunction of decreasing: A process that performs an excesssive decreasing the amount of the phenobarbital. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
hyperfunction of decreasing the amount of phenobarbital [Ground glass appearance]
Hyperfunction of phosphatidylinositol synthetic gene expression is a subtype of hyperfunction of glycerophospholipid synthesis gene expression: A process that performs an excesssive phosphatidylinositol synthetic gene expression.
hyperfunction of phosphatidylinositol synthetic gene expression
Chemical homeostasis imbalance is a subtype of homeostasis imbalance: A process that becomes lacking a chemical homeostastasis balance.
Hypofunction of phosphatidylinositol degradation is a subtype of hypofunction of glycerophospholipid degradation: A process that performs a decreased or insufficient phosphatidylinositol degradation.
hypofunction of phosphatidylinositol degradation
Changing balance of drug metabolism is a subtype of changing balance: A process that that changes the balance between break down and the continued presence of the drug.
Negative regulation of phosphatidylinositol degradation is a subtype of Negative regulation of glycerophospholipid degradation: A process that stops, prevents, or reduces the frequency, rate or extent of phosphatidylinositol degradation.
negative regulation of phosphatidylinositol degradation
Changing balance of drug metabolism is a subtype of changing balance: A process that that changes the balance between break down and the continued presence of the drug. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
changing balance of drug metabolism [Ground glass appearance]
Drug metabolism imbalance is a subtype of imbalance: A process that becomes lacking a homeostastasis balance of drug metabolism.
Hyperfunction of hosphatidic acid gene expression is a subtype of hyperfunction of glycerophospholipid synthesis gene expression: A process that performs an excesssive phosphatidic acid synthetic gene expression.
hyperfunction of hosphatidic acid gene expression
Hyperfunction of glucuronic acid conjugation for phenobarbital intermediate metabolite is a subtype of hyperfunction of glucuronic acid conjugation: A process that performs an excessive glucuronic acid conjugation. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
hyperfunction of glucuronic acid conjugation for phenobarbital intermediate metabolite [Ground glass appearance]
Hypofunction of phosphatidic acid degradation is a subtype of hypofunction of glycerophospholipid degradation: A process that performs a decreased or insufficient phosphatidic acid degradation.
hypofunction of phosphatidic acid degradation
Drug metabolism imbalance is a subtype of imbalance: A process that becomes lacking a homeostastasis balance of drug metabolism. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
drug metabolism imbalance [Ground glass appearance]
Negative regulation of phosphatidic acid degradation is a subtype of Negative regulation of glycerophospholipid degradation: A process that stops, prevents, or reduces the frequency, rate or extent of phosphatidic acid degradation.
negative regulation of phosphatidic acid degradation
Drug metabolism imbalance is a subtype of imbalance: A process that becomes lacking a homeostastasis balance of drug metabolism. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of liver tumor via ground glass appearance.
drug metabolism imbalance [Ground glass appearance (severe) - tumorigenesis]
Compound accumulation in liver is a subtype of accumulation of xenobiotics: A process that keeps compound in the liver. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (severe).
chemcal compound accumulation in liver [Ground glass appearance (severe)]
Increasing sphingophopholipid material is a subtype of increasing materials for lipid formation: A process that changes the amount of sphingophopholipid material to be larger.
Increasing sphingomyelin material is a subtype of increasing sphingophopholipid material: A process that changes the amount of sphingomyelin material to be larger.
Increasing sphingomyelin material is a subtype of increasing sphingophopholipid material: A process that changes the amount of sphingomyelin material to be larger. This process is dependent on the genetic and can constitute the course of Phospholipidosis (genetic).
increasing sphingomyelin material [Phospholipidosis - genetic- sphingomyelin disorder ]
Sphingomyelin metabolism imbalance is a subtype of sphingophopholipid metabolism imbalance: A process that becomes lacking a homeostastasis balance of sphingomyelin metabolism.
Increase in fatty acid inflow into hepatocyte is a subtype of increasing quantity: A process that changes the fatty acid inflow into the hepatocyte to be larger. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
increase in fatty acid inflow into hepatocyte [Phpspholipidosis]
Hyperfunction of sphingomyelin synthetic gene expression is a subtype of hyperfunction of sphingophospholipid synthesis gene expression: A process that performs an excesssive sphingomyelin synthetic gene expression.
hyperfunction of sphingomyelin synthetic gene expression
Phenobarbital accumulation in liver is a subtype of compound accumulation in liver: A process that keeps phenobarbital in the liver. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (severe).
phenobarbital accumulation in liver [Ground glass appearance (severe)]
Hypofunction of sphingomyelin degradation is a subtype of hypofunction of phosphosphingolipid degradation: A process that performs a decreased or insufficient sphingomyelin degradation.
hypofunction of sphingomyelin degradation
Smooth endoplasmic reticulum proliferation in hepatocyte is a subtype of endoplasmic reticulum proliferation in hepatocyte: A process that becomes larger in the number of smooth endoplasmic reticulum in hepatocyte(s). This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (sustained) .
smooth endoplasmic reticulum proliferation in hepatocyte (sustained) [Ground glass appearance]
Negative regulation of sphingophopholipid degradation is a subtype of negative regulation of phospholipid degradation: Any process that stops, prevents, or reduces the frequency, rate or extent of the sphingophospholipid catabolic process.
negative regulation of sphingophopholipid degradation
The totality of all processes through which ground glass appearance accompanied with hypertrophy is realized.
ground glass appearance with hypertrophy
Negative regulation of sphingomyelin catabolic process is a subtype of negative regulation of sphingophopholipid degradation: Any process that stops, prevents, or reduces the frequency, rate or extent of the sphingomyelin catabolic process.
negative regulation of sphingomyelin catabolic process
Hyperfunction of moving A to the inside of B is a subtype of hyperfunctioning: A process that performs an excesssive moving A to the inside of B.
hyperfunction of moving A to the inside of B
A role played by the entity which receives energy and transmits operand(s).
Any process involved in the maintenance of an internal steady state of phospholipid within an organism or cell. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
maintaining phospholipid homeostasis [Phospholipidosis]
Moving drug to the inside of liver is a subtype of moving A to the inside of B: A process that of the movement of drug into hepatocytes.
The totality of all processes through which the sphingomyelin disorder is realized. This causal process is heredity.
Dysfunction of sphingomyelin degradation is a subtype of dysfunction of phosphosphingolipid degradation: A process that performs an abnormal and incomplete sphingomyelin degradation.
dysfunction of sphingomyelin degradation
Dysfunction of sphingomyelin degradation is a subtype of dysfunction of phosphosphingolipid degradation: A process that performs an abnormal and incomplete sphingomyelin degradation. This process is dependent on the sphingomyelin disorder and can constitute the course of Phospholipidosis.
dysfunction of sphingomyelin degradation [Phospholipidosis - genetic- sphingomyelin disorder]
Sphingomyelinase gene mutation is a subtype of phopholipase gene mutation: A process that changes the sequence of a sphingomyelinase gene. This process is dependent on the genetic and can constitute the course of Phospholipidosis (genetic).
sphingomyelinase gene mutation [Phospholipidosis - genetic- sphingomyelin disorder ]
Increasing pressure is a subtype of changing pressure: A process that changes the pressure of the object to be higher.
related quality: http://purl.obolibrary.org/obo/PATO_0001576
Sphingomyelin accumulation in lysosome is a subtype of sphingophospholipid accumulation in lysosome: A process that keeps sphingomyelin in the lysosome. This process is dependent on the sphingomyelin disorder and can constitute the course of Phospholipidosis (genetic).
sphingomyelin accumulation in lysosome [Phospholipidosis - genetic- sphingomyelin disorder]
Sphingomyelin accumulation in lysosome of nervous system is a subtype of sphingomyelin accumulation in lysosome: A process that keeps sphingomyelin in the lysosome of nervous system.
sphingomyelin accumulation in lysosome of nervous system
Severe sphingomyelin accumulation in lysosome of nervous system is a subtype of sphingomyelin accumulation in lysosome of nervous system: A process that keeps sphingomyelin in the lysosome of nervous system severely. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Niemann Pick Disease Type A (severe).
sphingomyelin accumulation in lysosome of nervous system [Niemann Pick Disease Type A (severe) ]
Protein binding by NAPQI is a subtype of protein binding: Interacting between a protein and NAPQI.
Compound accumulation in liver is a subtype of accumulation of xenobiotics: A process that keeps compound in the liver.
Compound accumulation in lysosome is a subtype of accumulation of xenobiotics: A process that keeps compound in the lysosome. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
chemical compound accumulation in lysosome [Phospholipidosis (severe)]
From the LOPAC library we found that a group of tricyclic analogs including imipramine, clomipramine, trimipramine and amitriptyline used as antidepressant in the clinic were correctly identified as PLD inducers.
PERK signal transduction system is a subtype of pathway system. This entity has sub-parts and has a goal of transmitting signals via PERK as a systemic context.
Glycerophospholipid accumulation in lysosome is a subtype of phospholipid accumulation in lysosome: A process that keeps glycerophospholipid in the lysosome.
glycerophospholipid accumulation in lysosome
Increase in fatty acid inflow into hepatocyte is a subtype of increasing quantity: A process that changes the fatty acid inflow into the hepatocyte to be larger. The degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
increaing in fatty acid inflow into hepatocyte [Phpspholipidosis (severe)]
Leaking is a subtype of moving A to the outside of B: A process that lets gas or liquid flow through.
Increase in fatty acid inflow into hepatocyte is a subtype of increasing quantity: A process that changes the fatty acid inflow into the hepatocyte to be larger. The digree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
increase in fatty acid inflow into hepatocyte [Phpspholipidosis(moderate)]
Phosphatidic acid accumulation in lysosome is a subtype of glycerophospholipid accumulation in lysosome: A process that keeps phosphatidic acid in the lysosome.
phosphatidic acid accumulation in lysosome
Increasing phospholipid material is a subtype of increasing quantity: A process that changes the amount of phospholipid material to be larger. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (moderate).
increasing phospholipid material[Phospholipidosis (moderate )]
Phosphatidylserine accumulation in lysosome is a subtype of glycerophospholipid accumulation in lysosome: A process that keeps phosphatidylserine in the lysosome.
phosphatidylserine accumulation in lysosome
Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of phospholipids. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (moderate).
hyperfunction of phospholipid biosynthesis [Phospholipidosis (moderate) ]
Phosphatidylcholine accumulation in lysosome is a subtype of glycerophospholipid accumulation in lysosome: A process that keeps phosphatidylcholine in the lysosome.
phosphatidylcholine accumulation in lysosome
S1P inactivation is a subtype of molecular inactivation: A process that changes the activity of the S1P (Sphingosine-1-phosphate) to be lower.
Phosphatidylglycerol accumulation in lysosome is a subtype of glycerophospholipid accumulation in lysosome: A process that keeps phosphatidylglycerol in the lysosome.
phosphatidylglycerol accumulation in lysosome
Hyperfunction of phospholipid biosynthesis is a subtype of hyperfunction of biosynthesis: A process that performs an excessive phospholipid biosynthesis. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
hyperfunction of phospholipid biosynthesis [Phospholipidosis (severe) ]
Phosphatidylethanolamine accumulation in lysosome is a subtype of glycerophospholipid accumulation in lysosome: A process that keeps phosphatidylethanolamine in the lysosome.
phosphatidylethanolamine accumulation in lysosome
positive regulation of phospholipid biosynthetic process [Phospholipidosis]
AMPK - inactivation state (canonical)[lipidosis]
PERK-eIF2a signal transduction system is a subtype of pathway system. This entity has sub-parts and has a goal of transmitting signals via PERK and eIF2a as a systemic context.
PERK signal transduction system is a subtype of pathway system. This entity has sub-parts and has a goal of transmitting signals via PERK as a systemic context. This entity is dependent on ER stress.
PERK signal transduction system [ER stress]
Moving drug to the inside of liver is a subtype of moving A to the inside of B: A process that of the movement of drug into a liver. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
moving drug to the inside of liver [Ground glass appearance]
Toxic course dependent process is a subtype of primitive process: A process that can constitute the toxic course.
Phospholipidosis dependent process is a subtype of toxic course dependent process: A process that can constitute the course of phospholipidosis .
ER stress dependent process is a subtype of toxic course dependent process: A process that can constitute the course of endoplasmic reticulum stress.
Malfunctioning of hepatic blood circulation is a subtype of malfunctioning process: A process that cannot perform hepatic blood circulation function appropriately or cannot realize it at all.
malfunctioning of hepatic blood circulation
Moving phenobarbital to the inside of liver is a subtype of moving A to the inside of B: A process that of the movement of phenobarbital into a liver. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
moving phenobarbital to the inside of liver [Ground glass appearance]
Hepatic steatosis dependent process is a subtype of toxic course dependent process: A process that can constitute the course of hepatic steatosis (fatty degeneration).
MMP inactivation by TIMP1 is a subtype of inactivating: A process that changes the activity of the MMP to be lower by TIMP1. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
Hypofunction of ATP biosynthesis is a subtype of hypofunction of biosynthesis: A process that performs a decreased or insufficient ATP biosynthesis.
Hypofunction of phospholipid deradation by phospholipase is a subtype of hypofunction of phospholipid degradation: A process that performs a decreased or insufficient phospholipid deradation by phospholipase.
hypofunction of phospholipid deradation by phospholipase
Hyperfunction of increasing is a subtype of hyperfunctioning: A process that performs an excessive function of increasing.
PERK-eIF2a signal transduction system is a subtype of pathway system. This entity has sub-parts and has a goal of transmitting signals via PERK and eIF2a as a systemic context. This entity is dependent on the translation attenuation of ER stress.
Hyperfunction of phospholipid synthesis gene expression is a subtype of hyperfunction of gene expression: A process that performs an excesssive phospholipid synthetic gene expression.
hyperfunction of phospholipid synthesis gene expression
Cell death dependent process is a subtype of toxic course dependent process: A process that can constitute the course of hepatocyte cell death.
Ground glass degeneration is a subtype of toxic course dependent process: A process that can constitute the course of ground glass appearance.
ground glass degeneration dependent process
Eosinophlic granular degeneration dependent process is a subtype of toxic course dependent process: A process that can constitute the course of eosinophilicgranular degeneration.
eosinophlic granular degeneration dependent process
Oxidative stress dependent process is a subtype of toxic course dependent process: A process that can constitute the course of oxidative stress.
Toxic course dependent chemical entity is a subtype of chemical entity. This entity can participate in a specific toxic course.
ATF6 signal transduction system is a subtype of pathway system. This entity has sub-parts and has a goal of transmitting signals via ATF6 as a systemic context.
In the imbalance model, the basic units are as follows: 1) a functioning process (supply) for biological defense and maintaining homeostasis; 2) a functional demand process (demand) as toxic activity; 3) balance/imbalance between toxic activity and defense processes; and 4) outcome from organelles, cells, or tissues to the organ exhibiting toxicity manifestations. This entity is step 3: a state of balance between toxic activity and defense processes.
In the imbalance model, the basic units are as follows: 1) a functioning process (supply) for biological defense and maintaining homeostasis; 2) a functional demand process (demand) as toxic activity; 3) balance/imbalance between toxic activity and defense processes; and 4) outcome from organelles, cells, or tissues to the organ exhibiting toxicity manifestations. This entity indicates step 3: a state of imbalance between toxic activity and defense processes.
In the imbalance model, the basic units are as follows: 1) a functioning process (supply) for biological defense and maintaining homeostasis; 2) a functional demand process (demand) as toxic activity; 3) balance/imbalance between toxic activity and defense processes; and 4) outcome from organelles, cells, or tissues to the organ exhibiting toxicity manifestations. This entity indicates step 1: a state of functioning (supply) for biological defense and maintaining homeostasis.
Cell part damage is a subtype of damaging: A process that injuries the structure of the cellular part as the direct or indirect result of an external force.
Membrane damage is a subtype of damaging: A process that injuries the structure of the membrane as the direct or indirect result of an external force.
Dysfunction of mitochondrial fatty acid beta-oxidation (severe) is a subtype of hypofunction of fatty acid beta-oxidation: A process that performs a decreased or insufficient fatty acid beta-oxidation severely. This entity is a specific course-dependent process. This process can constitute the course of Alcholic fatty liver.
dysfunction of mitochondrial fatty acid degradation [Alchoric fatty liver]
The level of degree is very high in comparison to the medium.
Dysfunction of lipid degradation is a subtype of dysfunctioning: A process that performs an abnormal and incomplete lipid degradation.
The level of degree is lower than medium.
Inflammasome activation is a subtype of activating: A process that changes the activity of the inflammasome to be higher. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
NLRP3 agonists tested, including ATP and particulate activators, induce ROS and ROS blockade by chemical scavengers suppresses inflammasome activation. The source of ROS is currently unclear, but one or several NADPH oxidases are implicated, as suppression of the common p22 subunit inhibits inflammasome activation (Dostert et al., 2008); alternatively, ROS may be of mitochondrial origin.
The phosphorylation of ADP to ATP that accompanies the oxidation of a metabolite through the operation of the respiratory chain. Oxidation of compounds establishes a proton gradient across the membrane, providing the energy for ATP synthesis. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
In the imbalance model, the basic units are as follows: 1) a functioning process (supply) for biological defense and maintaining homeostasis; 2) a functional demand process (demand) as toxic activity; 3) balance/imbalance between toxic activity and defense processes; and 4) outcome from organelles, cells, or tissues to the organ exhibiting toxicity manifestations. This entity indicates step 2: a state of functional demand as toxic activity.
Malfunctioning of mitochondrial ATP synthesis coupled electron transfer is a subtype of malfunctioning process: A process that cannot perform a respiratory electron transport chain appropriately or cannot realize it at all. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
malfunctioning of mitochondrial ATP synthesis coupled electron transfer [lipidosis]
Negative regulation of respiratory electron transport chain is a subtype of negative regulation process: Any process that stops, prevents or reduces the frequency, rate or extent of mrespiratory electron transport chain. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
negative regulation of respiratory electron transport chain [lipidosis]
Negative regulation of oxidative phosphorylation is a subtype of negative regulation process: Any process that stops, prevents or reduces the frequency, rate or extent of the oxidative phosphorylation. This entity is a specific course-dependent process. This process can constitute the course of lipidosis.
negative regulation of oxidative phosphorylation [Lipidosis]
ATF6 signal integration system is a subtype of pathway system. This entity has sub-parts and has a goal of transmitting signals and a gene regulation via ATF6 as a systemic context.
NAPQI accumulation is a subtype of accumulation of substances in a biological object: A process that keeps NAPQI (N-acetyl-p-benzoquinone imine) within a biological object(s). NAPQI is an intermediate metabolite of the paracetamol and plays a role as a toxic substance in the body.
Hypofunction of maintaining lysosome homeostasis is a subtype of hypofunctioning: A process that performs a decreased or insufficient maintaining lysosome homeostasis. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
hypofunction of maintaining lysosome homeostasis [Phospholipidosis (severe) ]
Preventing is a type of functioning process of meta-function of "ToPrevent". Two meta-functions "ToAllow" and "Toprevent" are concerned with the undesirable side effects of functions. A function fa having positive effects on the side effect of a function ft1 is said to have a meta-function “to allow the side-effects of ft1”. The “undesirable side effect” is defined in a relation with another function ft2 or the whole system. The “positive effect” means such a causal relation that increase of the focused attribute of fa causes decrease of the side effect. If a serious trouble (e.g., faults) will be caused in a function ft2 when a function fa is not achieved, function fa is said to have a meta-function “to prevent malfunction of ft2”. For example, the “to super-heat” function of the boiler prevents malfunction of the turbine, because the steam of low temperature would damage the turbine blade by water particles. For almost all fa performing a ToAllow meta-function for ft1, in general, there exists a ToPrevent meta-function for another function ft2.
Providing is a subtype of metafunctioning process. When a function fa generates (or transfers) the materials which another function ft intentionally processes, the function fa is said to perform a meta-function “to provide material” for the function ft. The material of ft can be basically defined as input objects (entity or energy) which will be a part of the output objects on which the function ft focuses.
Abnormality of membrane is a subtype of changing abnormal cellular structure: A process that changes the membrane stucture abnormally.
Driving is a type of functioning process of meta-function. The function which generates or transfers a driving energy is said to have meta-function “driving”. For example, the “to heat water” function of the boiler has a ToDrive meta-function for the “to generate torque” function of the turbine , because the amount of the heat energy transferred by the heating has a proportional causal relation to the torque and is consumed by the rotation.
Enabling is a subtype of meta-functioning process. To enable is a meta-function that sets conditions for other functions to work correctly.
Cytochrome P450 activation is a subtype of molecular activation: A process that changes the activity of the cytochrome P450 to be higher.
Importing substances into hepatocyte vascular side (sinusoidal side) membrane is a subtype of transport: A process of the directed movement of substances into hepatocyte vascular side (sinusoidal side) membrane. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
Uptake of bile salts from sinusoidal blood into hepatocyte is predominantly sodium dependent
importing substances into hepatocyte vascular side (sinusoidal side) membrane [Cholestasis]
ATF6-CHOP signal integration system is a subtype of ATF6 pathway system. This entity has sub-parts and has a goal of transmitting signals and a gene regulation via ATF6 and CHOP as a systemic context.
Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of phospholipids. And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (moderate).
positive regulation of phospholipid biosynthetic process [Phospholipidosis (moderate) ]
Increasing phospholipid material is a subtype of increasing quantity: A process that changes the amount of phospholipid material to be larger. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
increasing phospholipid material[Phospholipidosis ]
Sphingophospholipid accumulation in lysosome is a subtype of phospholipid accumulation in lysosome: A process that keeps sphingophospholipid in the lysosome.
sphingophospholipid accumulation in lysosome
Sphingomyelin accumulation in lysosome is a subtype of sphingophospholipid accumulation in lysosome: A process that keeps sphingomyelin in the lysosome.
Calcium ion homeostasis imbalance is a subtype of chemical homeostasis imbalance: A process that becomes lacking a calcium ion homeostastasis balance.
Hypofunction of xenobiotic glucuronidation is a subtype of decreasing function of: A process that performs a decreased or insufficient xenobiotic glucuronidation.
hypofunction of glucuronic acid conjugation
hypofunction of xenobiotic glucuronidation
phenobarbital - tumor promoting factor [Ground glass appearance]
A process that becomes lacking a homeostastasis balance of the sphingomyelin metabolism. This process is dependent on the genetic and can constitute the course of Phospholipidosis (genetic).
sphingomyelin metabolism imbalance [Phospholipidosis - genetic- sphingomyelin disorder ]
Hypofunction of phospholipase transport to lysosome is a subtype of hypofunction of transport: A process that performs a decreased or insufficient phospholipase transport to lysosome .
hypofunction of phospholipase transport to lysosome
Changing abnormal cellular structure is a subtype of changing structure: A process that changes the structure of the cell abnormally.
Negative regulation of oxidative phosphorylation is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of oxodative phosphorylation.
negative regulation of oxidative phosphorylation
Keeping amount of phospholipid in lysosome is a subtype of keeping amount: A process that maintaining the amount of lysosomal phospholipid. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (normal).
keeping amount of phospholipid in lysosome (normal condition) [Phospholipidosis]
Glutathione deficiency is a subtype of malfunctioning process: A process that lacks performing the glutathione function required.
Most of the genes commonly regulated in mouse and human were involved in lipid metabolism and many represented known PPARalpha targets, including CPT1A, HMGCS2, FABP1, ACSL1, and ADFP. Several genes were identified that were specifically induced by PPARalpha in human (MBL2, ALAS1, CYP1A1, TSKU) or mouse (Fbp2, lgals4, Cd36, Ucp2, Pxmp4).
Hypofunction of glutathione conjugation is a subtype of hypofunction of drug metabolism: A process that performs a decreased or insufficient glutathione conjugation.
Phospholipid metabolism imbalance is a subtype of imbalance: A process that becomes lacking a homeostastasis balance of phospholipid metabolism. This process is dependent on the genetic and can constitute the course of Phospholipidosis (genetic).
phospholipid metabolism imbalance [Phospholipidosis - genetic]
Phospholipid metabolism imbalance is a subtype of imbalance: A process that becomes lacking a homeostastasis balance of phospholipid metabolism. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (mild).
phospholipid metabolism imbalance [Phospholipidosis (mild)]
Phospholipid metabolism imbalance is a subtype of imbalance: A process that becomes lacking a homeostastasis balance of phospholipid metabolism. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
phospholipid metabolism imbalance [Phospholipidosis (severe) ]
In the imbalance model, the basic units are as follows: 1) a functioning process (supply) for biological defense and maintaining homeostasis; 2) a functional demand process (demand) as toxic activity; 3) balance/imbalance between toxic activity and defense processes; and 4) outcome from organelles, cells, or tissues to the organ exhibiting toxicity manifestations. This entity is a compound state that includes step 1 to 4, and the toxic activity level is higher (Very High, VH) than usual to imbalance and toxicity manifestations.
toxicological imbalance VH (toxic action)
In the imbalance model, the basic units are as follows: 1) a functioning process (supply) for biological defense and maintaining homeostasis; 2) a functional demand process (demand) as toxic activity; 3) balance/imbalance between toxic activity and defense processes; and 4) outcome from organelles, cells, or tissues to the organ exhibiting toxicity manifestations. This entity is a compound state that inculdes step 1 to 4. The defense performance level and the functional demand level are high, as a result, keeping the balance. This state reflects the adaptation in the body.
toxicological balance H=H (maintining homeostasis at higher level)
In the imbalance model, the basic units are as follows: 1) a functioning process (supply) for biological defense and maintaining homeostasis; 2) a functional demand process (demand) as toxic activity; 3) balance/imbalance between toxic activity and defense processes; and 4) outcome from organelles, cells, or tissues to the organ exhibiting toxicity manifestations. This entity is a compound state that inculdes step 1 to 4. The defense performance level is higher (H) than daily life; however, the functional demand level is Very high(VH), which leads to the imbalance and leads to toxicity manifestation.
Phospholipid metabolism balance is a subtype of maintaining balance: A process that keeps a balance of phospholipid metabolism. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense).
phospholipid metabolism balance [Phospholipidosis (adaptation)]
The directed movement of the organic anion into hepatocyte vascular side (sinusoidal side) membrane during cholestasis. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
importing anion into hepatocyte vascular side (sinusoidal side) membrane [cholestasis] [Cholestasis]
The sodium-dependent movement of the organic anion into hepatocyte vascular side (sinusoidal side) membrane. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
Uptake of bile salts from sinusoidal blood into hepatocyte is predominantly sodium dependent, whichi is mediated by the NTCP (sodium/bile acid cotransporter; SLC10A1) in a polar manner at the basolateral plasma membrane of hepatocytes
organic anion import into hepatocyte vascular side (sinusoidal side) membrane [cholestasis] [Cholestasis]
Catalysis role of the reaction: H(2)O + sphingomyelin = ceramide + choline phosphate + H(+).
Lipidosis marker is predicted by SVM, which is possible to participate in the course of lipidosis as a gene product. Predicted gene profile:Human/in vitro/Hepatocyte/
Negative regulation of enzyme activation is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of enzyme activation.
negative regulation of enzyme activation
Negative regulation of sphingomyelin catabolic process is a subtype of negative regulation of sphingophopholipid degradation: Any process that stops, prevents, or reduces the frequency, rate or extent of the sphingomyelin catabolic process. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (sphingomyelin disorder).
negative regulation of sphingomyelin catabolic process [sphingomyelin disorder ]
SPON2-α4β1 integrin signaling activated RhoA and Rac1, increased F-actin reorganization, and promoted M1-like macrophage recruitment. F-Actin accumulation also activated the Hippo pathway by suppressing LATS1 phosphorylation, promoting YAP nuclear translocation, and initiating downstream gene expression. However, SPON2-α5β1 integrin signaling inactivated RhoA and prevented F-actin assembly, thereby inhibiting HCC cell migration.
Upregulation of Spondin-2 protein expression correlates with poor prognosis in hepatocellular carcinoma. Kaplan-Meier analysis revealed that HCC patients who showed high levels of cytoplasmic SPON2 protein had poorer survival.
Increasing free radical is a subtype of increasing quantity: A process that changes the amount of free radicals to be larger.
Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2-alpha/EIF2S1) on 'Ser-52' during the unfolded protein response (UPR) and in response to low amino acid availability. Converts phosphorylated eIF-2-alpha/EIF2S1 either in a global protein synthesis inhibitor, leading to a reduced overall utilization of amino acids, or to a translation initiation activator of specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion. Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1 (CCND1). Involved in control of mitochondrial morphology and function.
Generating signal is a subtype of generating: A process that produces a signal as an output. This entity is a specific course-dependent process. This process can constitute the course of Signaling pathway.
Increasing glycerophospholipid material is a subtype of increasing materials for lipid formation: A process that changes the amount of glycerophospholipid material to be larger. This process is dependent on the sphingophospholipid disorder and can constitute the course of Phospholipidosis.
increasing glycerophospholipid material [Phospholipidosis - sphingophospholipid disorder]
Phosphatidylinositol 3-kinase signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal transmitted by the phosphatidylinositol 3-kinase (PI3K).
phosphatidylinositol 3-kinase signaling (primitive)
AKT signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal transmitted by the intracellular serine/threonine kinase protein kinase B (also called AKT). This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense) .
AKT signaling (primitive) [Phospholipidosis (excessive defense) ]
Glucose-6-Phosphatase Catalytic Subunit [Ground glass appearance]
G6PC (canonical)[Ground glass appearance]
The protein encoded by this gene is a transmembrane glycoprotein that is a member of the protein kinase superfamily. This protein is a receptor for members of the epidermal growth factor family. EGFR is a cell surface protein that binds to epidermal growth factor. Binding of the protein to a ligand induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation. Mutations in this gene are associated with lung cancer. [provided by RefSeq, Jun 2016]
Catalysis of the reaction: a phospholipid + H2O = 1,2-diacylglycerol + a phosphatidate.
mannose-6-phosphate receptor [Phospholipidosis]
Sphingomyelin accumulation in lysosome is a subtype of sphingophospholipid accumulation in lysosome: A process that keeps sphingomyelin in the lysosome. This entity is a specific course-dependent process. This process can constitute the course of Niemann Pick Disease Type A/ B (severe).
severe sphingomyelin accumulation in lysosome [Niemann Pick Disease Type A/ B (severe)]
CYP2C8 Is a Novel Target of Peroxisome Proliferator-Activated Receptor α in Human Liver. CYP2C8 mRNA and protein levels were induced by bezafibrate. CYP2C8 promoter activity was increased by ectopic expression of PPARα in HepG2 cells, with a further increase after bezafibrate (∼18-fold), 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio acetic acid (∼10-fold) treatment, or the antidiabetic drug rosiglitazone, all known PPAR activators. CYP2C8, but not CYP2C9 or CYP2C19, is transcriptionally upregulated by PPARα activation in primary human hepatocytes.
Sphingomyelin accumulation in lysosome is a subtype of sphingophospholipid accumulation in lysosome: A process that keeps sphingomyelin in the lysosome. This entity is a specific course-dependent process. This process can constitute the course of Niemann Pick Disease Type B.
severe sphingomyelin accumulation in lysosome [Niemann Pick Disease Type B]
Malfunction of mitochondria is a subtype of malfunctioning process: A process that cannot perform a mitochondrial function appropriately or cannot realize it at all. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
A size change process in which the size of liver and spleen is increasing. This entity is a specific course-dependent process. This process can constitute the course of Niemann-Pick Disease Type B.
splenohepatomegaly [Niemann Pick Disease Type B]
A size change process in which the size of liver and spleen is increasing.
Pulmonary infection is a subtype of pathogen colonization: A process that makes pathogen such as microorganism (bacteria, virus, mycoplasma, etc.) present in the lung to increase the number. This entity is a specific course-dependent process. This process can constitute the course of Niemann Pick Disease Type B.
pulmonary infection [Niemann Pick Disease Type B]
Sphingomyelin accumulation in lysosome is a subtype of sphingophospholipid accumulation in lysosome: A process that keeps sphingomyelin in the lysosome. This entity is a specific course-dependent process. This process can constitute the course of Niemann Pick Disease Type A.
severe sphingomyelin accumulation in lysosome [Niemann Pick Disease Type A]
A process that becomes lacking a homeostastasis balance of the sphingomyelin metabolism. This entity is a specific course-dependent process. This process can constitute the course of Niemann Pick Disease Type B.
sphingomyelin metabolism imbalance [Niemann Pick Disease Type B]
A size change process in which the size of liver and spleen is increasing. This entity is a specific course-dependent process. This process can constitute the course of Niemann-Pick Disease Type A.
splenohepatomegaly [Niemann Pick Disease Type A]
Hypofunction of nervous system functioning is a subtype of hypofunctioning: A process that performs a decreased or insufficient nervous system functioning. This entity is a specific course-dependent process. This process can constitute the course of Niemann-Pick Disease Type A.
hypofunction of nervous system functioning [Niemann Pick Disease Type A]
Hypofunction of nervous system functioning is a subtype of hypofunctioning: A process that performs a decreased or insufficient nervous system functioning.
hypofunction of nervous system functioning
System dependent functional molecule is asubtype of chemical entity. This entity is dependent on a system for functioning.
Signaling transduction system dependent molecule is a subtype of system dependeny functional molecule. This entity is dependent on a signal transduction system for functioning.
signal transduction system dependent molecule
Lipid accumulation in hepatocyte is a subtype of lipid strorage in hepatocyte: A process that keeps lipids in hepatocytes. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (moderate).
lipid accumulation in hepatocyte [Phospholipidosis(moderate)]
A process that becomes lacking a homeostastasis balance of the sphingomyelin metabolism. This process is dependent on the sphingomyelin disorder and can constitute the course of sphingomyelin disorder.
sphingomyelin metabolism imbalance [Phospholipidosis - sphingomyelin disorder]
Phospholipid accumulation in lysosome is a subtype of phospholipid accumulation: A process that keeps phospholipid in the lysosome. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (mild).
phospholipid accumulation in lysosome [Phospholipidosis (mild)]
Hyperfunction of increasing the amount of drug is a subtype of hyperfunction of increasing: A process that performs an excessive increase in the amount of drug.
hyperfunction of increasing the amount of drug
Receiving abnormal protein signal by PERK is a subtype of receiving signal: A process that recognizes another object and changes into an abnormal protein (e.g., misfolded protein, etc.) signal by PERK. This process is dependent on the refolding and can constitute the course of ER stress via protein refolding.
receiving abnormal protein signal by PERK [ER stress - refolding]
Hyperfunction of increasing the amount of drug is a subtype of hyperfunction of increasing: A process that performs an excessive increase in the amount of drug. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
hyperfunction of increasing the amount of drug [Ground glass appearance]
Receptor molecule is a subtype of signaling dependent molecule. This entity is dependent on a signal transduction system and can participate in signaling process.
receptor molecule [signal transduction system]
Hypofunction of ceramide degradation is a subtype of hypofunction of lipid degradation: A process that performs a decreased or insufficient ceramide degradation.
Decreasing production quantity of protein is a subtype of decreasing quantity: A process that changes the production quantity of the protein to be lower.
decreasing production quantity of protein
Phosphatidylinositol accumulation in lysosome is a subtype of glycerophospholipid accumulation in lysosome: A process that keeps phosphatidylinositol in the lysosome.
phosphatidylinositol accumulation in lysosome
Hyperfunction of decreasing is a subtype of hyperfunctioning: A process that performs an excesssive decreasing amount or decreasing number of objects.
Signaling molecule is a subtype of signaling dependent molecule. This entity is dependent on a signal transduction system and can participate in signaling process.
signaling molecule [signal transduction system]
Hyperfunction of decreasing the amount of drugs is a subtype of hyperfunction of decreasing: A process that performs an excesssive decreasing the amount of drugs.
hyperfunction of decreasing the amount of drugs
Dissociation of PERK:BIP heterodimer is a subtype of detaching: A process that disaggregates PERK-BIP heterodimers into BIP and PERK. This process is dependent on the refolding and can constitute the course of ER stress.
Dissociation of PERK:BIP Heterodimer [ER stress - refolding]
Hyperfunction of decreasing the amount of drug is a subtype of hyperfunction of decreasing: A process that performs an excesssive decreasing the amount of drugs. And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (moderate) .
hyperfunction of decreasing the amount of drug [Ground glass appearance (moderate) ]
Receiving signal in PERK signal transduction pathway is a subtype of receiving signal: A process that recognizes another object and changes into a signal in a PERK signal transduction pathway. This entity is a specific course-dependent process. This process can constitute the course of PERK pathway.
receiving signal in PERK signal transduction pathway [PERK pathway]
Hyperfunction of hepatocyte proliferation is a subtype of hyperfunction of cell proliferation: The multiplication or reproduction of hepatocytes, resulting in the expansion of a cell population. Hepatocytes form the main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
hyperfunction of hepatocyte proliferation [Ground glass appearance]
Dissociation of PERK:BIP heterodimer is a subtype of detaching: A process that disaggregates PERK-BIP heterodimers into BIP and PERK. This process is dependent on the apoptosis and can constitute the course of ER stress.
Dissociation of PERK:BIP Heterodimer [ER stress - apoptosis]
Hyperfunction of increasing the amount of phenobarbital is a process of performing an excessive function of increasing the amount of drugs. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
hyperfunction of increasing the amount of phenobarbital [Ground glass appearance]
PERK - signal sensor (canonical)[Perk signalling system]
Increasing the amount of phenobarbital is a subtype of increasing amount of drugs. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
increasing the amount of phenobarbital [Ground glass appearance]
Drug metabolism imbalance is a subtype of imbalance: A process that becomes lacking a homeostastasis balance of drug metabolism. And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (moderate) .
drug metabolism imbalance[Ground glass appearance (moderate) ]
Lipid accumulation in hepatocyte is a subtype of lipid strorage in hepatocyte: A process that keeps lipids in hepatocytes. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
lipid accumulation in hepatocyte [Phospholipidosis(severe)]
S1P inactivation is a subtype of molecular inactivation: A process that changes the activity of the S1P (Sphingosine-1-phosphate) to be lower. This entity is a specific course-dependent process. This process can constitute the course of phospholipidosis.
Malfunctioning of mitochondrial ATP synthesis coupled electron transpor is a subtype of malfunctioning process: A process that cannot perform a respiratory electron transport chain appropriately or cannot realize it at all.
malfunctioning of mitochondrial ATP synthesis coupled electron transpor
Changing balance is a subtype of changing relationship between operands: A process that changes the balance between operands.
Compound accumulation in liver is a subtype of accumulation of xenobiotics: A process that keeps compound in the liver. And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (moderate) .
chemical compound accumulation in liver [Ground glass appearance (moderate) ]
Phospholipidosis dependent chemical compound is a subtype of toxic course dependent chemical entity. This entity (drug) can participate in the course of phospholipidosis.
phospholipidosis dependent chemical compound
Hepatic fibrosis is a subtype of fibrosis: A process that replaces liver tissues to fibrous connective tissues, usually as a consequence of inflammation or other injury. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense).
hepatic fibrosis [Phospholipidosis (excessive defense)]
Making existence of xenobiotics is a subtype of making existence of foreign substance: A process that makes xenobiotics to be present in a cell, organelle, or an organism.
PERK - signaling factor (canonical)[Perk signalling system]
TGF beta receptor signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal transmitted by the TGF beta receptor (transforming growth factor beta receptor) on the surface of a cell, starting with a ligand binding to a TGFR. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense).
TGF beta receptor signaling (primitive) [Phospholipidosis (excessive defense)]
TGF beta receptor signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal transmitted by the TGF beta receptor (transforming growth factor beta receptor) on the surface of a cell, starting with a ligand binding to a TGFR.
Decreasing mitochondrial membrane potential is a subtype of decreasing membrane potential: A process that changes the electrical potential of a mitochondrial membrane to be lower.
decreasing mitochondrial membrane potential
The chemical reactions and pathways resulting in the formation of heme, any compound of iron complexed in a porphyrin (tetrapyrrole) ring, from less complex precursors. This entity is a specific course-dependent process. This process can constitute the course of lipidosis.
lysophosphatidic acid [Phospholipidosis]
Hypofunction of PPAR alpha regulated gene expression is a subtype of hyporfunction of gene expression: A process that performs an PPARa trgulated gene expression. This entity is a specific course-dependent process. This process can constitute the course of NASH.
hypofunction of PPARa regulated gene expression [NASH]
Cyp4a11 relates to cardiovascular abnormality (blood pressure, etc.).
The PPARalpha agonist Wy14643 induced CYP4A11 mRNA in confluent cultures of HepG2 cells stably expressing the murine PPARalpha-E282G mutant. This mutant exhibits a significantly decreased ligand-independent trans-activation and can be activated by Wy14643 to a level similar to that of wild-type PPARalpha.
Treatment of HepaRG cells with all-trans-retinoic acid resulted in a strong decrease in CYP4A11 gene expression and apoprotein content and, furthermore, was associated with a 50% decrease in the microsomal lauric acid hydroxylation activity. Such a strong suppression of CYP4A11 expression by retinoids could have a major impact on fatty acid metabolism in the liver.
Hypofunction of PPARa regulated gene expression is a subtype of Hypofunction of phospholipase gene expression is a subtype of hypofunction of transcription, DNA-templated: A process that performs a decreased or insufficient PPARa regulated gene expression.
hypofunction of PPARa regulated gene expression
A process that changes the activity of the target object by PERK. This entity is a specific course-dependent process. This process can constitute the course of PERK pathway.
changing activity of target molecule by PERK [PERK pathway]
The process that results in the movement of mitochondriall DNA from the mitochondria.
The process that results in the movement of mitochondriall DNA from the mitochondria. This entity is a specific course-dependent process. This process can constitute the course of lipidosis.
release of DNA from mitochondria [lipidosis]
Catalysis role of the phosphorylation of an amino acid residue in a protein, usually according to the reaction: a protein + ATP = a phosphoprotein + ADP.
A role played by the entity which inhibits bile acid transport by BSEP.
inhibitor role of BSEP bile acid transport
A role played by the entity which stops, prevents, or reduces the frequency, rate or extent of trasnport.
The sodium-independent movement of the organic anion into hepatocyte vascular side (sinusoidal side) membrane. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
Sodium-independent uptake of conjugated and unconjugated bile acids is performed by members of the organic anion-transporting polypeptides (OATPs). OATPs also transport numerous drugs and hepatotoxicants.
The sodium-independent portion of bile salt uptake is mediated by OATPs
organic anion import into hepatocyte vascular side (sinusoidal side) membrane [Cholestasis]
Gene expression by CHOP (DDIT3, GADD153) is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) by CHOP (DDIT3, GADD153).
gene expression by CHOP (DDIT3, GADD153)
The appearance of interleukin-1 beta due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
Increasing volume of mitochondria is a changing process to change the volume of the mitochondria to increase. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
increasing volume of mitochondria [Mitochondrial disorder]
TNF-α induces mitochondrial perturbations such as swelling with a lighter matrix and abnormal morphological alterations in the membrane. In addition, TNF-α-induced mitochondrial swelling causes a bursting of the membrane leading to an interference between respiratory chain complexes I and III.
Generating energy is a subtype of generating: A process that produces energy as an output.
An attribute inhering in a bearer by an observation.
Electrophiles formation is a subtype of biosynthetic process: A process that that generates electrophiles. Electrophile is a reagent that forms a bond to its reaction partner (the nucleophile) by accepting both bonding electrons from that reaction partner. This entity is a specific course-dependent process. This process can constitute the course of lipidosis (NASH).
Caspase Recruitment Domain-Containing Protein 5
Increased Fibroblast Growth Factor 21 in Obesity and Nonalcoholic Fatty Liver Disease:We found increased serum FGF21 levels in patients with either NAFLD or NASH and for the first time we report that FGF21 mRNA expression in human liver is significantly increased in NAFLD.
ER stress and PPARα activation contribute to carcinogenesis in a fatty liver: a modest increase in the expression of lipoprotein lipase (LPL) and fibroblast growth factor 21 (FGF21) in both Acox1−/− and Acox1−/−/ob/ob mouse liver (Fig. 5A). Significant increases in microsomal triglyceride transfer protein (MTP) were found in Acox1−/−/ob/ob mouse liver (Supplemental Fig. S2B). MTP regulates hepatic lipid secretion and may play a role in the reduction of hepatic steatosis in these mice
A rifamycin that is a a semisynthetic antibiotic derived from Amycolatopsis rifamycinica (previously known as Amycolatopsis mediterranei and Streptomyces mediterranei)
Caspase Recruitment Domain-Containing Protein 5 [lipidosis]
PYD And CARD Domain Containing [lipidosis]
Hepatic CYP3A4 mRNA expression in NASH was 69% lower than control livers. CYP3A4 gene luciferase activity in the livers of NAFLD mice was 38% lower than that of controls. Lipid-loaded Huh7 human hepatoma cells had a 38% reduction in CYP3A4 activity and 80% lower CYP3A4 mRNA expression compared with the control. CYP3A activity is reduced in human NAFLD in addition to mouse and in vitro cell models of the disease.
The cytokine-mediated down-regulation of CYP3A4 (Werk and Cascorbi, 2014) in the course of the inflammatory response via the JAK/STAT (Janus kinase/Signal Transducer and Activator of Transcription) pathway (Jover et al., 2002 ) seem to be clinically relevant in NAFLD and diabetic patients due to circulating cytokines. Additionally, it has been suggested that the hepatic CYP3A4 expression is probably down-regulated by FGF21 (fibroblast growth factor 21) through the receptor-mitogen-activated protein kinase (MAPK) pathway which leads to reduced gene transcription (Woolsey et al., 2016).
Nonalcoholic Fatty Liver Disease and Diabetes Are Associated with Decreased CYP3A4 Protein Expression and Activity in Human Liver.
Cytochrome P450 inactivation is a subtype of molecular inactivation: A process that changes the activity of the Cytochrome P450 to be lower.
Cytochrome P450 inactivation is a subtype of molecular inactivation: A process that changes the activity of the Cytochrome P450 to be lower. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
cytochrome P450 inactivation [lipidosis]
The cytokine-mediated down-regulation of CYP3A4 (Werk and Cascorbi, 2014) in the course of the inflammatory response via the JAK/STAT (Janus kinase/Signal Transducer and Activator of Transcription) pathway (Jover et al., 2002 ) seem to be clinically relevant in NAFLD and diabetic patients due to circulating cytokines.
CYP3A4 -inactitication state (human)[lipidosis]
Negative regulation of bile acid and bile salts export from the hepatocyte is a subtype of negative regulation of transport: A process that stops, prevents, or reduces the frequency, rate or extent of bile acid and bile salts export from the hepatocyte.
negative regulation of bile acid and bile salts export from the hepatocyte
The process of assisting in the disassembly of non-covalent linkages in a protein or protein aggregate, often where the proteins are in a non-functional or denatured state. This entity is a specific course-dependent process. This process can constitute the course of lipidosis.
Both NASH and HCC development were dependent on TNF produced by inflammatory macrophages that accumulate in the MUP-uPA liver in response to hepatocyte ER stress.
Fenofibrate is a fibric acid derivative used in the therapy of hypertriglyceridemia and dyslipidemia. Fenofibrate therapy is associated with mild and transient serum aminotransferase elevations and with rare instances of acute liver injury, which can be severe and prolonged and lead to significant hepatic fibrosis.
fenofibrate [Eosinophilic granular degeneration]
Clofibrate is a fibric acid derivative used in the therapy of hypertriglyceridemia and dyslipidemia. Clofibrate therapy is associated with mild and transient serum aminotransferase elevations and with rare instances of acute liver injury.
clofibrate [Eosinophilic granular degeneration]
A role played by the entity which transmits signals.
EIF2a phosphorylation is a subtype of phosphorylation: The process of introducing a phosphate group into eIF2a.
A role played by the entity which enables the energy-independent passage of anions across a lipid bilayer down a concentration gradient.
Gene regulation pathway is a subtype of pathway: Sequence of reactions to regulate genes following signaling.
Rsad2 may act as a modulator of lipid droplet contents and lipid biosynthesis.
ATF6 activation is a subtype of molecular activation: A process that changes the activity of the ATF6 (Activating Transcription Factor 6) to be higher.
ATF6 activation is a subtype of molecular activation: A process that changes the activity of the ATF6 (Activating Transcription Factor 6) to be higher. This process is dependent on the refolding and can constitute the course of ER stress.
Acumulation of bile pigment in bile canaliculus is a subtype of bile pigment deposition: The aggregation of bile pigmentin a particular location in a bile canaliculus.
acumulation of bile pigment in bile canaliculus
Negative regulation of phospholipase-mediated phospholipid degradation by CAD is a subtype of negative regulation of phospholipid degradation: A process that stops, prevents, or reduces the frequency, rate or extent of phospholipase-mediated phospholipid deradation regulated by CAD. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (latent).
negative regulation of phospholipase-mediated phospholipid degradation by CAD [Phospholipidosis (latent)]
A role played by the entity which stops, prevents, or reduces the frequency, rate or extent of translational initiation.
related process GO:0036495 negative regulation of translation initiation in response to endoplasmic reticulum stress GO:0010998: regulation of translational initiation by eIF2 alpha phosphorylation (Any process that modulates the frequency, rate or extent of translation initiation in response to stress by the phosphorylation of eIF2 alpha.) GO:0036492 eiF2alpha phosphorylation in response to endoplasmic reticulum stress inverse of GO:0036497 eIF2alpha dephosphorylation in response to endoplasmic reticulum stress
negative regulator role of translational initiation
Hypofunction of biosynthesis is a subtype of hypofunctioning: A process that performs a decreased or insufficient biosynthesis.
Hypofunction of transport is a subtype of hypofunctioning: A process that performs a decreased or insufficient transport.
Increasing blood glucose lebvel is a subtype of increasing concentration: A process that changes the blood glucose concentration in the blood to be higher.
Decresing pressure is a subtype of changing pressure: A process that changes the pressure of the object to be lower.
Increasing BUN concentration is a subtype of increasing concentration: A process that changes the Blood Urea Nitrogen (BUN) concentration to be higher.
Glutathione depletion dependent chemical entity is a subtype of toxic course dependent chemical entity. This entity can participate in the course of glutathione depletion.
glutathione depletion dependent chemical entity
Glutathione depletion dependent molecule is a subtype of toxic course dependent chemical entity. This gene can participate in the course of glutathione depletion as a gene product. Gene profile:Human/in vitro/Hepatocyte/
glutathione depletion dependent molecule (human in vitro)
G6PD (predicted)(human)[Glutathione depletion]
MIST1 (predicted) [Glutathione depletion]
BLHA15 (predicted)(human)[Glutathione depletion]
Mist1 suppressed expression of cholangiocytic markers such as Sox9, Sox17, Ck19, and Grhl2. CYP3A metabolic activity was significantly induced by Mist1 in this hepatoblast culture. In particular, the expression level of Cyp3a11, an important drug metabolic gene, was highly induced by Mist1.
HISTH1H2BG (predicted)(human)[Glutathione depletion]
Glucose metabolism induces mono-ubiquitination of histone H2B in mammalian cells.
Electrophiles formation is a subtype of biosynthetic process: A process that that generates electrophiles. Electrophile is a reagent that forms a bond to its reaction partner (the nucleophile) by accepting both bonding electrons from that reaction partner. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
electrophiles formation [Glutathione depletion]
Glutathione depletion dependent chemical compound is a subtype of toxic course dependent chemical entity. This entity (drug) can participate in the course of glutathione depletion.
glutathione depletion dependent chemical compound
Glutathione conjugation is a subtype of drug metabolism phase II: Glutathione conjugation is a detoxication reaction. Four types of activation reaction have been recognized: direct-acting compounds, conjugates that are activated through cysteine conjugate beta-lyase, conjugates that are activated through redox cycling and lastly conjugates that release the original reactive parent compound. The glutathione S-transferases have three connections with the formation of biactivated conjugatesto make them more soluble for excretion. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
glutathione conjugation [Glutathione depletion]
Hyperfunction of glutathione conjugation is a subtype of hyperfunction of drug metabolism phase II: A process that performs an excessive glutathione conjugation. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
hyperfunction of glutathione conjugation [Glutathione depletion]
Any process that stops, prevents, or reduces the frequency, rate or extent of DNA repair process. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance .
Glutathione depletion dependent molecule is a subtype of toxic course dependent chemical entity. This gene can participate in the course of glutathione depletion as a gene product. Gene profile:Rat/Liver/
glutathione depletion dependent molecule (rat)
Glutathione Synthetase [Glutathione depletion]
Hyperfunction of glutathione synthetic gene expression is a subtype of hyperfunction of gene expression: A process that performs an excesssive glutathione synthetic gene expression. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
hyperfunction of glutathione synthetic gene expression [Glutathione depletion]
An enzyme that catalysis of the reaction: L-gamma-glutamyl-L-cysteine + ATP + glycine = ADP + glutathione + 2 H(+) + phosphate.
DDB2 -inactivation (canonical)[Ground glass appearance]
Inhibition of GSH is achieved by buthionine-S-sulfoximine (BSO), which inhbits ints gammma-GCL. Casarett & Doull's Toxicology: The Basic Science of Poisons, Eighth Edition
Any process that stops, prevents, or reduces the frequency, rate or extent of glutathione biosynthetic process. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
negative regulation of glutathione biosyntheric process [Glutathione depletion]
Any process that stops, prevents, or reduces the frequency, rate or extent of glutathione biosynthetic process.
down regulation of glutathione anabolism
down regulation of glutathione biosynthesis
negative regulation of glutathione anabolism
negative regulation of glutathione biosynthesis
negative regulation of glutathione formation
negative regulation of glutathione synthesis
negative regulation of glutathione biosynthetic process
JNK suppresses apoptosis via phosphorylation of the proapoptotic Bcl-2 family protein BAD
JNK can promote apoptosis by two distinct mechanisms. In the first mechanism targeted at the nuclear events, activated JNK translocates to the nucleus and transactivates c-Jun and other target transcription factors (TF). JNK can promote apoptosis by increasing the expression of pro-apoptotic genes through the transactivation of c-Jun/AP1-dependent or p53/73 protein-dependent mechanisms
GCLC - inactivated state (canonical)[Glutathione depletion]
GCLC inactivation is a subtype of is a subtype of molecular inactivation: A process that changes the activity of the GCLC to be lower. This entity is a specific course-dependent process. This process can constitute the course of glutathione depletion.
GCLC inactivation [Glutathione depletion]
Changing protein structure is a subtype of changing structure: A process that changes the stucture of the protein. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Hypofunction of forming disulfide bond is a subtype of hypofunctioning: A process that performs a decreased or insufficient forming disulfide bond.
Hypofunction of protein synthesis is a subtype of hypofunction of biosynthesis: A process that performs a decreased or insufficient protein synthesis.
Hypofunction of forming disulfide bond is a subtype of hypofunctioning: A process that performs a decreased or insufficient forming disulfide bond. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
hypofunction of forming disulfide bond [ER stress]
Carnitine palmitoyltransferase I (CPT I) is a mitochondrial membrane protein that converts long-chain fatty acyl-CoA molecules to their corresponding acylcarnitine molecules. The resulting acylcarnitines are then available for transport into the mitochondrial matrix where they can undergo fatty acid oxidation. Mitochondrial fatty acid oxidation by the liver provides an alternative source of fuel when glycogen reserves are significantly reduced, most often due to fasting or other intercurrent illness. The pathway fuels ketogenesis for metabolism in peripheral tissues that cannot oxidize fatty acids. copyright University of Washington
tunicamycin-protein glycosylation inhibitor [ER stress]
Hypofunction of protein glycosylation is a subtype of hypofunctioning: A process that performs a decreased or insufficient protein glycosylation.
The totality of all processes through which the phospholipidosis is realized. This entity represents latent phospholipidosis, which describes the course of processes before toxic manifestation. In the drug exposure situation in phospholipidosis, it is known that CADs affect biological functioning. CADs bind to lysosomal membranes and form a complex with phospholipids, which negatively regulates phospholipid degradation. Therefore, the defence system cannot perform a ‘high’ level, i.e. there is a lack of adaptation. Under normal conditions, although the cell system can maintain the balance between increasing and decreasing phospholipid at a ‘medium’ level, in this state, the cellular system is in what is called the latent stage.
The following four processes were involved in the induction of phospholipidosis; (1) Inhibition of lysosomal phospholipase activivity (2) Inhibition of lysosomal enzyme transport, as demonstrated by the down-regulation of genes involved in lysosomal enzyme transport (3) Enhanced phospholipid biosynthesis, which is supported by the up- regulation of fatty acid biosynthesis-related genes (4) Enhanced cholesterol biosynthesis, as shown by the up-regulation of cholesterol biosynthesis-related genes Increased cholesterol biosynthesis is considered to be an indirect trigger for the reasons: (1) The accumulation of sphingomyelin occurs concurrently with the increase in cholesterol in visceral tissues (e.g., spleen) in patients with Niemann-Pick type C disease (NPC), which is caused by a genetic defect in the cholesterol trafficking protein NPC1 or, in far fewer patients, the sterol regulating protein HE1 (Blanchette-Mackie, 2000; Harzer et al., 2003; Vanier, 1983). (2) The induction of lamellar myelin-like bodies and the accumulation of free cholesterol occur in cultured mouse macrophages that have been incubated with acetylated low density lipoprotein or acyl-CoA:cholesterol acyl- transferase inhibitor (McGookey and Anderson, 1983; Robenek and Schmitz, 1988). In addition, the up- or down-regulation of transporter genes (e.g., facilitated glucose transporter) and genes that control the cell cycle (e.g., cyclin G2) may also be involved. Increase in phospholipid synthesis and impaired membrane recycling and lysosomal enzyme sorting dynamics are also occured.
Negative regulation ofglycosylation is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of glycosylation. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
negative regulation of glycosylation [ER stress]
Catalysis role of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate.
The Endoplasmic Reticulum Chaperone GRP170: From Immunobiology to Cancer Therapeutics.
A role played by the entity which determines the rate of a reaction by the slowest step.
mitochondrial fatty acid βbeta-oxidation rate-limiting enzyme role
CPT1 inactivation is a subtype of is a subtype of molecular inactivation: A process that changes the activity of the activating CPT1 with a nuclear receptor role to be lower. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
CPT1 inactivation is a subtype of molecular inactivation: A process that changes the activity of the CPT1 to be lower.
Negative regulation of mitochondrial beta oxidation is a subtype of negative regulation of decomposing: Any process that stops, prevents or reduces the frequency, rate or extent of mitochondrial fatty acid beta oxidation.
negative regulation of mitochondrial beta oxidation
Negative regulation of mitochondrial beta oxidation is a subtype of negative regulation of decomposing: Any process that stops, prevents or reduces the frequency, rate or extent of mitochondrial fatty acid beta oxidation. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
negative regulation of mitochondrial beta oxidation [lipidosis]
CPT1 -inactivation state(canonical)[lipidosis]
tamoxifen -fatty acid oxidation inhibitor [Lipidosis]
valproic acid - fatty acid oxidation inhibitor [Lipidosis]
Accumulation of abnormal proteins in ER is a subtype of accumulation of abnormal proteins: A process that keeps abnormal protein(s) in the ER (endoplasmic reticulum). This entity is a specific course-dependent process. This process can constitute the course of ER stress (mild).
accumulation of abnormal proteins in ER [ER stress (mild) ]
A role played by the gene which has a characteristic profile of gene expression change in a specific toxic mechanism.
Enterohepatic circulation is a subtype of changing between operands: Bile salts secreted by the liver pass into the intestine, are absorbed in large part by the ileum, and return to the liver by way of the portal vein.
Bile salts (>90%) are absorbed along the small intestine and transported back by the portal blood to the liver. They are taken up into hepatocytes and re-secreted into the canaliculi. This round trip of bile salts between the intestine and the liver is termed enterohepatic circulation.
Meloxicam is a long acting nonsteroidal antiinflammatory drug (NSAID) available by prescription only and used in therapy of chronic arthritis. Meloxicam has been linked to rare instances of acute, clinically apparent liver injury.
amiodarone - fatty acid oxidation inhibitor
Changing state is a subtype of changing an operand: A process that changes the state of the object.
Mutation is a subtype of changing an operand: A process that changes the nucleotide sequence of DNA randomly and permanently.
The totality of all processes through which mitochondrial damage is realized.
Mitochondrial disorder dependent process is a subtype of toxic course dependent process: A process that can constitute the course of mitochondrial disorder.
mitochondrial disorder dependent process
ATP depletion is a subtype of depleting: A process that lessens markedly in the amount of adenosine triphosphate (ATP) . This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
MPTP activation by a combination of elevated intramitochondrial Ca2+ and oxidative stress promotes the collapse of transmembrane ion gradients, resulting in membrane depolarization, uncoupling of oxidative phosphorylation and ATP depletion. Under conditions of low ATP levels, the cells are unable to maintain structural and functional integrity, including ion homeostasis. This results in outer membrane permeabilization and cytochrome c release into the cytoplasm to initiate pro-apoptotic signals.
Consistent with this, high glucose induces mitochondrial fragmentation, ROS production, loss of mitochondrial membrane potential, and ATP depletion in several rodent and human cell models. Moreover, in vitro treatment of liver cells with saturated fatty acids (palmitic and stearic acids) reproduces mitochondrial dysfunction found in NASH, including decreasing cellular ATP content and mtDNA-encoded oxidative phosphorylation (OXPHOS) subunit expression, coupled with increased oxidative stress. In addition to its ability to promote de novo lipogenesis and block β-oxidation of fatty acids, fructose consumption seems to cause a drop in ATP and an elevation of uric acid, which can further induce mitochondrial oxidative stress. More precisely, dietary-induced hypercholesterolemia causes oxidative stress, loss of mitochondrial membrane potential, reduction in ATP content, loss of mitochondrial cristae, and hepatic steatosis in mice.
Negative regulation of respiratory electron transport chain is a subtype of negative regulation process: Any process that stops, prevents or reduces the frequency, rate or extent of mrespiratory electron transport chain. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
negative regulation of respiratory electron transport chain [Mitochondrial disorder]
The chemical reaction resulting in the formation of reactive oxygen species, any molecules or ions formed by the incomplete one-electron reduction of oxygen. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
reactive oxygen species biosynthetic process [Mitochondrial disorder]
Furthermore, enhanced mtFAO without concomitant up‐regulation of the mitochondrial respiratory chain (MRC) activity induces reactive oxygen species (ROS) overproduction within different MRC components upstream of cytochrome c oxidase. This event seems to play a significant role in the initiation of oxidative stress and subsequent development of nonalcoholic steatohepatitis (NASH) in some individuals. Experimental investigations also pointed to a progressive reduction of MRC activity during NAFLD, which could impair energy output and aggravate ROS overproduction by the damaged MRC. Furthermore, high glucose levels promote ROS overproduction within hepatocytes, thus favoring oxidative stress and mitochondrial dysfunction. It is likely that this event triggers a vicious cycle since mitochondrial ROS are able to oxidatively damage nearby MRC enzymes and mtDNA
These results suggest that the observed dysfunction of complex I in hepatic mitochondria from CDD animals could be attributed, at least in part, to ROS-induced cardiolipin alterations. Long-chain free fatty acids which accumulate in nonalcoholic fatty liver are considered the initial source of this ROS damaging cycle. These compounds have been shown to promote ROS production in mitochondria, although the mechanism(s) underlying this effect is still unclear. Thus, the CL-dependent alterations of the ETC organization in supercomplexes could be another factor contributing to ROS generation and to mitochondrial bioenergetic decay in NAFLD.
During nonalcoholic fatty liver disease (NAFLD), mitochondria also produce ROS that damage hepatocytes, trigger inflammation, and contribute to insulin resistance.
We found a consistent and significant increase of mitochondrial ROS along with a parallel increase of total cellular ROS levels specifically in mC9ORF72 cells compared to both healthy control and mTDP-43 fibroblasts (Fig. 2e-​-ff).
Alcohol-mediated damage of mitochondrial DNA (mtDNA) also impairs cellular energy metabolism via enhanced formation of reactive oxygen species (ROS). Alcohol decreases the activity of the oxidative phosphorylation (OXPHOS) complexes and increases ROS production, leading to mitochondrial stress or dysfunction.
Collectively, these data suggest that enforced PCK1 expression triggers glucose-deprived liver cancer cell death by causing truncated gluconeogenesis, energy crisis, TCA cycle cataplerosis and high ROS levels.
Exogenous H2O2 activates AMPK indirectly in myotubes by decreasing the ATP/ADP ratio. We conclude that AMPK activity in response to redox changes is not due to direct action on AMPK itself, but is a secondary consequence of redox effects on other processes, such as mitochondrial ATP production.
The imbalance of respiratory complex activity during the development of NAFLD and its progression to NASH leads to increased mitochondrial reactive oxygen species (ROS), causing oxidative mitochondrial DNA (mtDNA) damage, mitochondria structural abnormalities, and lipid peroxidation. Mitochondrial ROS (mtROS) and lipid peroxidation also trigger proinflammatory cytokines such as interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1 beta (IL-1β), which are critical mediators of inflammation in NASH. Mitochondrial-derived ROS activate mitogen-activated protein kinases (MAPKs) including c-Jun N-terminal kinase (JNK). Phosphorylated JNK translocates to the mitochondria, where it binds to scaffold proteins inhibiting the mitochondrial respiratory chain and further increasing ROS production. Mitochondrial-derived ROS also activate AMP-activated protein kinase (AMPK) secondary to redox changes and mitochondrial ATP production. Mitochondrial ROS and oxidative stress can disrupt ER function leading to inappropriate release of calcium in liver parenchymal cells. Consistent with this, high glucose induces mitochondrial fragmentation, ROS production, loss of mitochondrial membrane potential, and ATP depletion in several rodent and human cell models. Saturated fats promote fatty liver and accumulation of lipotoxic byproducts including ceramides and diacylglycerols is associated with hepatic inflammation and mitochondrial ROS production resulting in liver cell death.
Accumulating evidence has shown that defective hepatic mitochondrial respiration characterized by damaged mitochondria accumulation can impair mitochondrial fatty acid β-oxidation, which sequentially causes various adverse consequences, such as excessive ROS, reduced ATP production, and hepatic fatty acid accumulation. In general, damaged mitochondria accumulation can cause excessive ROS production, which will destroy mitochondrial oxidative phosphorylation and substrate oxidation, thereby inhibiting fatty acid oxidative degradation and accelerating fatty acid accumulation .
Any process that increases the frequency, rate or extent of the passage or uptake of molecules by the mitochondrial membrane. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
positive regulation of mitochondrial membrane permeability [Mitochondrial disorder]
Moreover, saturated FAs are able to activate c‐Jun N‐terminal kinase and trigger the mitochondrial membrane permeability transition, thus inducing mitochondrial release of cytochrome c and apoptosis.
In fact, phospholipid peroxidation alters the structural organization of the mitochondrial bilayer, perturbing membrane fluidity and permeability. MPTP activation by a combination of elevated intramitochondrial Ca2+ and oxidative stress promotes the collapse of transmembrane ion gradients, resulting in membrane depolarization, uncoupling of oxidative phosphorylation and ATP depletion. Cardiolipin has been shown to be involved in several steps of the intrinsic pathway of the apoptotic process, including mitochondrial permeability transition pore (MPTP) and cytochrome c release from mitochondria. MPTP is defined as the sudden increase of mitochondrial inner membrane permeability to low molecular weight solutes (1.5 kDa) in response to many stimuli, including high levels of Ca2+ and oxidant stress. If MPTP opening is transient, the cell can recover; while in conditions of prolonged MPTP opening and ATP depletion, irreversible damage and cell death occur, predominantly through necrosis. In addition, CL oxidation seems to promote the permeabilization of the outer mitochondrial membrane, probably interacting with Bcl2 family proteins, such as Bax and Bid. Thus, oxidized CL may have a critical role in several steps of the apoptotic process such as: the translocation of t-Bid to mitochondria with subsequent oligomerization of Bax and Bak leading to membrane permeabilization; cytochrome c dissociation from the inner mitochondrial membrane; and activation of MPTP, followed by the release of this hemoprotein from the mitochondrial intermembrane space to the cytosol (Figure ​1).
A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
apoptotic process [Mitochondrial disorder]
Oxidative stress may cause damage at cellular level, such as membrane lipid peroxidation, cell degeneration and necrosis, cell death by apoptosis, proinflammatory cytokine expression, liver stellate cell activation and fibrogenesis. In liver cells, mitochondrial dysfunction plays a critical role by amplifying the apoptotic signal and integrating both pathways into a final common pathway.
Metabolic reprogramming by PCK1 promotes TCA cataplerosis, oxidative stress and apoptosis in liver cancer cells and suppresses hepatocellular carcinoma. Collectively, these data suggest that enforced PCK1 expression triggers glucose-deprived liver cancer cell death by causing truncated gluconeogenesis, energy crisis, TCA cycle cataplerosis and high ROS levels.
Bellanti et al. showed through targeted lipidomic analysis that rats fed diets rich in cholesterol exhibited increased toxic hepatic triol, which induces apoptosis and impaired mitochondrial respiration in vitro. Gan et al. showed that mitochondrial-free cholesterol deposition causes hepatocyte apoptosis and necrosis through c-Jun N-terminal kinase (JNK) activation, associated with increased high-mobility group box 1 (HMGB1), and cytolytic effects on neighboring hepatocytes driven by Toll-like receptor 4 (TLR4).
Decreasing mitochondrial membrane potential is a subtype of decreasing membrane potential: A process that changes the electrical potential of a mitochondrial membrane to be lower. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
decreasing mitochondrial membrane potential [Mitochondrial disorder]
MPTP activation by a combination of elevated intramitochondrial Ca2+ and oxidative stress promotes the collapse of transmembrane ion gradients, resulting in membrane depolarization, uncoupling of oxidative phosphorylation and ATP depletion.
Consistent with this, high glucose induces mitochondrial fragmentation, ROS production, loss of mitochondrial membrane potential, and ATP depletion in several rodent and human cell models. More precisely, dietary-induced hypercholesterolemia causes oxidative stress, loss of mitochondrial membrane potential, reduction in ATP content, loss of mitochondrial cristae, and hepatic steatosis in mice.
Bile acid and bile salt transport to hepatocyte is a subtype of bile acid and bile salt transport: A process that transports bile acid and bile salts within a hepatocyte by means of some agent such as a transporter or pore. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
After their uptake into hepatocytes, bile salts reach the canalicular plasma membrane, whch probably involves binding to cytoplasmic proteins.
bile acid and bile salt transport to hepatocyte [Cholestasis]
Decreasing membrane potential is a subtype of changing membrane potential: A process that changes the electrical potential across a membrane to be lower.
Malfunctioning of uncoupling is a subtype of malfunctioning process: A process that cannot perform uncoupling appropriately or cannot realize it at all. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
malfunctioning of uncoupling [Mitochondrial disorder]
A role played by the entity which enables the facilitated diffusion of a chloride (by an energy-independent process) involving passage through a transmembrane aqueous pore or channel without evidence for a carrier-mediated mechanism.
Negative regulation of mitochondrial gene expression is a subtype of negative regulation of gene expression: A process that stops, prevents, or reduces the frequency, rate or extent of mitochondrial gene expression. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
negative regulation of mitochondrial gene expression [Mitochondrial disorder]
GCLC inactivation is a subtype of molecular inactivation: A process that changes the activity of the GCLC to be lower.
Negative regulation of mitochondrial gene expression is a subtype of negative regulation of gene expression: A process that stops, prevents, or reduces the frequency, rate or extent of mitochondrial gene expression.
The process in which a mitochondrial gene's sequence is converted into a mature gene product or products (proteins or RNA). This includes the production of an RNA transcript as well as any processing to produce a mature RNA product or an mRNA or circRNA (for protein-coding genes) and the translation of that mRNA or circRNA into protein. Protein maturation is included when required to form an active form of a product from an inactive precursor form.
negative regulation of mitochondrial gene expression
Catalysis role of the reactions: ATP + a protein serine = ADP + protein serine phosphate; ATP + a protein threonine = ADP + protein threonine phosphate; and ATP + a protein tyrosine = ADP + protein tyrosine phosphate.
ATP:protein phosphotransferase (Ser/Thr- and Tyr-phosphorylating)
protein serine/threonine/tyrosine kinase
The emerging role of acyl-CoA thioesterases and acyltransferases in regulating peroxisomal lipid metabolism.
Toxicol Sci. 2016 Feb;149(2):312-25. Dose and Effect Thresholds for Early Key Events in a PPARα-Mediated Mode of Action. Thresholds varied widely by marker, from 2-fold (Pdk4 and proliferation LI) to 30-fold (Acot1) induction to reach hypothetical tumorigenic expression levels.
Acot1 is a sensitive indicator for PPARα activation after perfluorooctanoic acid exposure in primary hepatocytes of Sprague-Dawley rats.
Acyl-CoA Thioesterase 1 (ACOT1) Regulates PPARα to Couple Fatty Acid Flux with Oxidative Capacity During Fasting.
Lipid storage in liver is a subtype of lipid storage: The accumulation and maintenance in cells or tissues of lipids in the liver. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
lipid storage in liver [Mitochondrial disorder]
However, several hormonal and metabolic adaptations are set up in order to restrain hepatic fat accumulation, such as increased mitochondrial fatty acid oxidation (mtFAO). The expansion of hepatic lipids can be limited by different hormonal and metabolic adaptations leading to increased peroxisomal and mitochondrial FAO, as well as enhanced VLDL secretion (arrow 2).
As shown in Fig. 3c, H&E staining and Oil Red O staining showed that hepatic fat accumulation and immune cell infiltration were increased in alcohol-fed GDF15 KO mice compared to controls (Fig. 3c).
Recent studies also show that MAMs are important for hepatic insulin signaling, nutrient sensing, and glucose homeostasis. Therefore, disruption of ER-mitochondria contact sites could exacerbate hepatic lipid accumulation and miscommunication between organelles appears to be related to the pathology of hepatic metabolic diseases. Saturated fats promote fatty liver and accumulation of lipotoxic byproducts including ceramides and diacylglycerols is associated with hepatic inflammation and mitochondrial ROS production resulting in liver cell death. More precisely, dietary-induced hypercholesterolemia causes oxidative stress, loss of mitochondrial membrane potential, reduction in ATP content, loss of mitochondrial cristae, and hepatic steatosis in mice. Damaged mitochondria are usually eliminated by autophagy/mitophagy which is attenuated by lipid accumulation.
Hypofunction of mitochondrial fatty acid beta-oxidation is a subtype of hypofunction of fatty acid beta-oxidation: A process that performs a decreased or insufficient fatty acid beta-oxidation. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
Mitochondria are responsible for beta oxidation of fatty acids.Inhibition of mitochondrial beta -oxidationleads to hepatic steatosis and/or hepatotoxicity. DRUG INDUCED LIVER DISEASE CHAPTER 5, 3rd Ed. Editors: Neil Kaplowitz Laurie DeLev Hardcover ISBN: 9780123878175
hypofunction of mitochondrial fatty acid beta-oxidation [Mitochondrial disorder]
H2O2 produced by mitochondria induces antioxidant enzyme expression through AMPK-mediated activation of nuclear factor 2 (NRF2), and consistently, NRF2 knockout mice on a high-fat diet develop more severe NASH associated with decreased antioxidant response, reduced β-oxidation genes, and increased lipogenic genes. In addition to its ability to promote de novo lipogenesis and block β-oxidation of fatty acids, fructose consumption seems to cause a drop in ATP and an elevation of uric acid, which can further induce mitochondrial oxidative stress.
Recent study has found that hepatic fatty acid accumulation can cause damaged mitochondria accumulation, which can impair mitochondrial respiratory chain function and fatty acid oxidative degradation. Accumulating evidence has shown that defective hepatic mitochondrial respiration characterized by damaged mitochondria accumulation can impair mitochondrial fatty acid β-oxidation, which sequentially causes various adverse consequences, such as excessive ROS, reduced ATP production, and hepatic fatty acid accumulation. In general, damaged mitochondria accumulation can cause excessive ROS production, which will destroy mitochondrial oxidative phosphorylation and substrate oxidation, thereby inhibiting fatty acid oxidative degradation and accelerating fatty acid accumulation.
Hypofunction of lipid degradation is a subtype of hypofunction of decomposing: A process that performs a decreased or insufficient lipid degradation.
Hypofunction of fatty acid degradation is a subtype of hypofunction of lipid degradation: A process that performs a decreased or insufficient fatty acid degradation.
Hypofunction of fatty acid beta-oxidation is a subtype of hypofunction of fatty acid oxidation: A process that performs a decreased or insufficient fatty acid beta-oxidation.
hypofunction of fatty acid beta-oxidation
Changing iron ion concentration is a subtype of changing concentration: A process that changes the iron (Fe) concentration in the blood to be lower. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
changing iron ion concentration [Mitochondrial disorder]
Degradation of a mitochondrion by macroautophagy. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
We found evidence of autophagy/mitophagy in dynamic equilibrium with the biogenesis of novel mitochondria, particularly in mutant C9ORF72 fibroblasts where an increase of mitochondrial DNA content and mass, and of PGC1-α protein was observed. These results, together with electronic microscopy data showing few autophagic/mitophagic vacuoles in both mutant fibroblast groups (Fig. 1d), suggest an early activation of the autophagic process.
perhexiline - fatty acid oxidation inhibitor [lipidosis]
Mitochondrial damage dependent chemical entity is a subtype of toxic course dependent chemical entity. This entity can participate in the course of mitochondrial damage.
mitochondrial damage dependent chemical entity
Uncoupling dependent molecule is a subtype of toxic course dependent chemical entity. This gene can participate in the course of uncoupling of miochondrial damage as a gene product. Gene profile:Rat/Liver/
uncoupling dependent molecule (rat in vivo)
GENATLAS Biochemistry: uncoupling protein of inner mitochondrial membrane 3,with two forms,long and short missing C terminal 37 residues,dissipating the proton electrochemical gradient by uncoupling fuel oxidation from ADP-ATP conversion,highly expressed in skeletal muscle during development,regulated by nutritional factors,possible mediator of adaptive thermogenesis,involved in the variation of energy metabolism and obesity,regulated by PPARA and PPARG in mice,and dysregulated in states of insulin resistance,increased expression in function of obesity and in type 2 diabetes (NIDDM) UCP3 UniProtKB/Swiss-Prot Function: UCP are mitochondrial transporter proteins that create proton leaks across the inner mitochondrial membrane, thus uncoupling oxidative phosphorylation. As a result, energy is dissipated in the form of heat. May play a role in the modulation of tissue respiratory control. Participates in thermogenesis and energy balance. UCP3_HUMAN,P55916
UCP3 expression in liver modulates gene expression and oxidative metabolism in response to fatty acids, and sensitizes mitochondria to permeability transition.
Acot1 (mouse)[Eosinophilic granular degeneration]
Acot1 mRNA levels were increased by 90-fold in liver by treatment with Wy-14,643 and that Acot1 mRNA was also increased by 15-fold in the liver of hepatocyte nuclear factor 4alpha (HNF4alpha) knockout animals. Our study identified a direct repeat 1 (DR1) located in the Acot1 gene promoter in mouse, which binds the peroxisome proliferator-activated receptor alpha (PPARalpha) and HNF4alpha.
ACOT1 is a cytosolic enzyme with substrate selectivity for long chain (C12–C20) saturated-and monounsaturated acyl-CoAs. It is expressed mainly in liver, kidney, lung and heart in mouse. ACOT1 appears to modulate the cytosolic pool of long chain acyl-CoAs and FFA, potentially controlling ligand availability for the nuclear hormone receptors PPARα and HNF4α.
ACOT1 (Acyl-CoA Thioesterase 1) is a Protein Coding gene. Diseases associated with ACOT1 include Human Immunodeficiency Virus Infectious Disease. Among its related pathways are Metabolism and Fatty acid elongation. GO annotations related to this gene include hydrolase activity and palmitoyl-CoA hydrolase activity. An important paralog of this gene is ACOT2.
tamoxifen -mitochondrial respiratory chain inhibitor [Lipidosis]
The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose members display helicase and ATPase activities and which are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI and has sequence similarity to the yeast Swp73 protein. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]
Brg1/Brm-associated factor (BAF) 60c is a specific chromatin remodeling component for lipogenic gene transcription in liver.
Moving lipid to the hepatocyte is a subtype of moving A to the inside of B: A process of the movement of lipid into a hepatocyte. This entity is a specific course-dependent process. This process can constitute the course of eosinogranular degeneration.
moving lipid to the hepatocye [Eosinophilic granular degeneration]
Characterization of the fasting-induced adipose factor FIAF, a novel peroxisome proliferator-activated receptor target gene.
Peroxisome proliferator-activated receptor gamma target gene encoding a novel angiopoietin-related protein associated with adipose differentiation.
Rare loss-of-function mutations in ANGPTL family members contribute to plasma triglyceride levels in humans.
Inhibitory receptors bind ANGPTLs and support blood stem cells and leukaemia development. Nature 485: 656-660, 2012.
The circulating ANGPTL3 and ANGPTL 4 expression was significantly elevated in HCC cases compared to chronic hepatitis patients and controls
The totality of all processes through which eosinogranular degeneration accompanied with hypertrophy is realized.
eosinophilic granular degeneration with hypertrophy [toxic course]
The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members bind heparin and possess broad mitogenic and angiogenic activities. This protein has been implicated in diverse biological processes, such as limb and nervous system development, wound healing, and tumor growth. The mRNA for this gene contains multiple polyadenylation sites, and is alternatively translated from non-AUG (CUG) and AUG initiation codons, resulting in five different isoforms with distinct properties. The CUG-initiated isoforms are localized in the nucleus and are responsible for the intracrine effect, whereas, the AUG-initiated form is mostly cytosolic and is responsible for the paracrine and autocrine effects of this FGF. [provided by RefSeq, Jul 2008]
FGF-2 protects against H2O2-induced necrosis of H9C2 cardiomyocytes via the activation of the PI3K/Akt/FoxO3a pathway.
Fibroblast growth factor 2 protects against renal ischaemia/reperfusion injury by attenuating mitochondrial damage and proinflammatory signalling.
Increasing hepatocellular volume is a changing process to change the volume of the hepatocyte to increase. The degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
increasing hepatocellular volume (moderate) [Eosinophilic granular degeneration]
amiodarone -mitochondrial respiratory chain inhibitor [lipidosis]
Increasing hepatocellular volume is a changing process to change the volume of the hepatocyte to increase. The degree is mild. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
increasing hepatocellular volume (mild) [Eosinophilic granular degeneration]
STARD7 (StAR Related Lipid Transfer Domain Containing 7) is a Protein Coding gene. Diseases associated with STARD7 include Gestational Trophoblastic Tumor. Among its related pathways are Metabolism and Glycerophospholipid biosynthesis. GO annotations related to this gene include lipid binding. An important paralog of this gene is PCTP.
GTT1/StarD7, a novel phosphatidylcholine transfer protein-like highly expressed in gestational trophoblastic tumour: cloning and characterization.
StarD7 mediates the intracellular trafficking of phosphatidylcholine to mitochondria.
Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function.
Increasing hepatocellular volume is a changing process to change the volume of the hepatocyte to increase. The degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
increasing hepatocellular volume (severe) [Eosinophilic granular degeneration]
pergexiline -mitochondrial respiratory chain inhibitor [lipidosis]
A role played by the entity which negative regulates the oxidative phosphorylation.
oxidative phosphorylation inhibitor role
The totality of all processes through which a given diabetes instance is realized.
Hypofunction of electron transport coupled proton transport is a subtype of hypofunction of ion transport: A process that performs a decreased or insufficient electron transport coupled proton transport.
hypofunction of electron transport coupled proton transport
ibuprofen - oxidative phosphorylation inhibitor [lipidosis]
A role played by the entity which regulates the glutathione conjugation.
glutathione conjuation regulating agent role
Leaking proton ion is a subtype of leaking: A process that leaks the proton from the mitochondria. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
leaking proton ion [Mitochondrial disorder]
Enables the transfer of protons from mitochondrial intermembrane space into mitochondrial matrix, dissipating the proton gradient across the mitochondrial inner membrane established by the electron transport chain during the oxidative phosphorylation (proton leak). Proton leak uncouples the processes of electron transport/proton generation and ATP synthesis. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
oxidative phosphorylation uncoupling [mitochondrial disorder]
Fatty acid strorage is a subtype of accumulation of substances in a biological object: A process that keeps fatty acid in a biological object. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
fatty acid strorage [Mitochondrial disorder]
A second mechanism is ROS generation due to CYP2E1 overexpression and reduced levels of mtGSH. Whereas CYP2E1 induction could be secondary to higher levels of glucagon, FAs and KBs, reduced mtGSH could result from higher mitochondrial levels of cholesterol. Some lipid derivatives such as FAs can directly inhibit several enzymes involved in MRC and OXPHOS. Moreover, saturated FAs are able to activate c‐Jun N‐terminal kinase and trigger the mitochondrial membrane permeability transition, thus inducing mitochondrial release of cytochrome c and apoptosis. Numerous studies showed increased expression of PPARα in fatty liver. Different cues such as FAs, leptin, and IL6 could activate PPARα and its target genes involved in mtFAO (CPT1, MCAD), peroxisomal FAO (acyl‐CoA oxidase), and VLDL production (microsomal triglyceride transfer protein).
First, in murine livers, elevation of fatty acid delivery not only induced oxidative metabolism, but also amplified anaplerosis/cataplerosis and caused a proportional rise in oxidative stress and inflammation. Likewise, Pck1 knockdown did not cause lower fasting basal endogenous glucose production (Figure 4C) or GNG (Figure 4D) on a control diet, but it was sufficient to prevent the rise in these fluxes during a HFD.
PPARalpha activation is a subtype of activating nuclear receptor: A process that changes the activity of the activating PPAR alpha ( (Peroxisome Proliferator Activated Receptor Alpha)) with a nuclear receptor role to be higher. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
PPARalpha activation [Mitochondrial disorder]
Numerous studies showed increased expression of PPARα in fatty liver. Different cues such as FAs, leptin, and IL6 could activate PPARα and its target genes involved in mtFAO (CPT1, MCAD), peroxisomal FAO (acyl‐CoA oxidase), and VLDL production (microsomal triglyceride transfer protein). mtFAO in liver could be favored by increased levels of hormones and other circulating factors such as leptin, FGF21, and interleukin 6 (IL6). For instance, LCFA‐mediated PPARα activation increases the expression of the mitochondrial enzymes CPT1 and medium‐chain acyl‐CoA dehydrogenase (MCAD).
nimesulide [lipidosis - oxidative phosphorylation inhibitor]
A compound which plays an inhibition of glutathione conjugation.
Glutathione depletion dependent molecule is a subtype of toxic course dependent chemical entity. This gene can participate in the course of glutathione depletion as a gene product. Gene profile:caonical that described in textbooks or articles.
glutathione depletion dependent molecule (canonical)
Changing force is a subtype of changing quality: A process that changes the force of the object.
Regulation of lipolytic gene expression is a subtype of regulation of gene expression: A process that modulates the frequency, rate or extent of lipid degradation related gene expression. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
regulation of lipolytic gene expression [Eosinophilic granular degeneration]
Hypofunction of carbohydrate transport is a subtype of hypofunction of transport: A process that performs a decreased or insufficient carbohydrate transport.
Hyperfunction of drug metabolism phase I is a subtype of hyperfunctioning of drug metabolism: A process that performs an excessive drug metabolism phase I.
hyperfunction of drug metabolism phase I
Decreasing glycogen level is a subtype of decreasing quantity: A process that changes the amount of glycogen level to be lower.
Hyperfunction of Cyp gene expression is a subtype of hyperfunction of drug metabolizing enzyme gene expression: A process that performs an excesssive gene expression of cytochrome p450.
Hyperfunction of electron transport from NADH to cytochrome P450 is a subtype of hyperfunction of transport: A process that performs an excesssive electron transport from NADH to cytochrome P450.
hyperfunction of electron transport from NADH to cytochrome P450
Dioxins and dioxin-like compounds accumulation in liver is a subtype of compound accumulation in liver: A process that keeps dioxins and dioxin-like compoundsin the liver.
dioxins and dioxin-like compounds accumulation in liver
Negative regulation of heat generation is a subtype of negative regulation process: Any process that stops, prevents, or reduces the rate or extent of heat generation.
Mitotic G2/M transition checkpoint is a subtype of negative regulation of G2/M transition of mitotic cell cycle: A cell cycle checkpoint that detects and negatively regulates progression from G2 to M phase as part of a mitotic cell cycle.
Any process that stops, prevents, or reduces the frequency, rate or extent of glutathione conjugation process.
negative regulation of glutathione conjugation
Negative regulation of cell proliferation inhibitor expression is a subtype of negative regulation of gene expression: A process that stops, prevents, or reduces the frequency, rate or extent of cell proliferation inhibitor expression.
negative regulation of cell proliferation inhibitor expression
Hyperfunction of reduction is a subtype of hyperfunctioning: A process that performs an excesssive reduction.
Decreasing negative regulator of G1/S transition is a subtype of decreasing quantity: A process that chanes the quantity of the object with a negative regulator of G1/S role to be lower.
decreasing negative regulator of G1/S transition
Insufficient detoxification is a subtype of making insufficient: A process that lacks in detoxification.
Antioxidant gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature antioxidant gene product or products (proteins or RNA).
LPL (canonical)[Eosinophilic granular degeneration]
Hyprerfunction of anti-oxidative stress is a subtype of hyperfunctioning: A process that performs an excesssive response to oxidative stress.
Decreasing proton motive force is a subtype of decreasing force: A process that changes the force of proton generated by electrochemical proton gradient to be lower.
CAR binding is a subtype of binding: Interacting with CAR (constitutive androstane receptor) .
constitutive androstane receptor binding
Compound accumulation in liver is a subtype of accumulation of xenobiotics: A process that keeps compound in the liver. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
chemical compound accumulation in liver [Ground glass appearance]
Dysfunction of phospholipid degradation is a subtype of dysfunctioning: A process that performs an abnormal and incomplete phospholipid degradation. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (genetic).
dysfunction of phospholipid degradation [Phospholipidosis - genetic]
Phospholipid accumulation in lysosome is a subtype of phospholipid accumulation: A process that keeps phospholipid in the lysosome. This process is dependent on the sphingomyelin disorder and can constitute the course of Phospholipidosis (genetic).
phospholipid accumulation in lysosome [Phospholipidosis - genetic- sphingomyelin disorder ]
Liver malfunction is a subtype of organ malfunction: A process that does not perform liver function correctly or not functioning at all. This entity is a specific course-dependent process. This process can constitute the course of Niemann-Pick Disease Type A/ B.
liver malfunction [Niemann Pick Disease Type A/ B]
Spleen malfunction is a subtype of organ malfunction: A process that does not perform spleen function correctly. This entity is a specific course-dependent process. This process can constitute the course of Niemann-Pick Disease Type A/ B.
spleen malfunction [Niemann Pick Disease Type A/ B]
Organ malfunction is a subtype of malfunctioning process: A process that cannot perform organ(s) function appropriately or cannot realize it at all.
Liver malfunction is a subtype of organ malfunction: A process that does not perform liver function correctly or not functioning at all.
Spleen malfunction is a subtype of organ malfunction: A process that does not perform spleen function correctly.
In the imbalance model, the basic units are as follows: 1) a functioning process (supply) for biological defense and maintaining homeostasis; 2) a functional demand process (demand) as toxic activity; 3) balance/imbalance between toxic activity and defense processes; and 4) outcome from organelles, cells, or tissues to the organ exhibiting toxicity manifestations. The defense performance level and the functional demand level are moderate (M) under the normal condition and keeping the balance.
toxicological imbalance M=M (maintining homeostasis in the normal condition)
Compound excretion is a subtype of xenobiotics excretion: A process that takes a compound from a cell, organelle, or makes a clearance of it from the body.
Compound excretion is a subtype of xenobiotics excretion: A process that takes a compound from a cell, organelle, or makes a clearance of it from the body. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
chemical compound excretion [Phospholipidosis]
Decreasing demand for phospholipid degradation is a subtype of decreasing functional demand: A process that changes the functional demand for the phospholipid degradation to be lower. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
decreasing demand for phospholipid degradation [Phospholipidosis]
Decreasing demand is a subtype of decreasing quantity: A process that changes the quantity demanded to be lower.
Decreasing functional demand is a subtype of decreasing demand: A process that changes the functional demand to be lower.
Decreasing demand for phospholipid degradation is a subtype of decreasing functional demand: A process that changes the functional demand for the phospholipid degradation to be lower.
decreasing demand for phospholipid degradation
ceramide accumulation is a subtype of accumulation of substances in a biological object: A process that keeps ceramide in an organism, tissue, organelle, or cell. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense).
increasing phospholipid metabolite [Phospholipidosis (excessive defense)]
Decreasing phospholipid is a subtype of decreasing lipid: A process that changes the quantity of the phospholipid to be lower.
Decreasing phospholipid is a subtype of decreasing lipid: A process that changes the quantity of the phospholipid to be lower. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
decreasing phospholipid [Phospholipidosis]
Increasing lysosomal pH is a subtype of changing pH: A process that changes the pH in lysosome to be higher. And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (moderate).
increasing lysosomal pH [Phospholipidosis (moderate) ]
A process that stops, prevents, or reduces the frequency, rate or extent of phospholipid degradation. And the degree is mild. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (mild).
negative regulation of phospholipid degradation [Phospholipidosis (mild)]
Hypofunction of phospholipid degradation is a subtype of hypofunction of decomposing: A process that performs a decreased or insufficient phospholipid degradation. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (mild).
hypofunction of phospholipid degradation [Phospholipidosis (mild)]
Malfunctioning of phospholipid metabolism is a subtype of malfunctioning of controlling: A process that cannot perform a regulation of phospholipid metabolism appropriately or cannot realize it at all. The degree is mild. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (mild).
malfunctioning of phospholipid metabolism [Phospholipidosis (mild)]
Malfunctioning of phospholipid metabolism is a subtype of malfunctioning of controlling: A process that cannot perform a regulation of phospholipid metabolism appropriately or cannot realize it at all.
malfunctioning of phospholipid metabolism
Lysosome damage is a subtype of organelle damage. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
lysosome damage [Phospholipidosis (severe) ]
Lysosomal enzyme leakage is a subtype of leaking: A process that leaks the enzyme out from the lysosome. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
lysosomal enzyme leakage [Phospholipidosis (severe) ]
Lysosomal enzyme leakage is a subtype of leaking: A process that leaks the enzyme out from the lysosome.
Autolysis is a subtype of dissolving: The disintegration of a cell by rupture of the cell membrane by the action of their own enzymes. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
Dysfunction of phospholipid degradation is a subtype of dysfunctioning: A process that performs an abnormal and incomplete phospholipid degradation severely. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
dysfunction of phospholipid degradation [Phospholipidosis (severe) ]
Increasing drug metabolite is a subtype of increasing quantity: A process that changes the amount of drug metabolites to be higher. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
negative regulation of apoptotic process [Eosinophilic granular degeneration]
Negative regulation of insulin receptor signaling pathway is a subtype of negative regulation of signaling: Any process that stops, prevents, or reduces the frequency, rate or extent of insulin receptor signaling. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
negative regulation of insulin receptor signaling pathway [ER stress]
Negative regulation of insulin receptor signaling pathway is a subtype of negative regulation of signaling: Any process that stops, prevents, or reduces the frequency, rate or extent of insulin receptor signaling.
negative regulation of insulin receptor signaling pathway
Any process that stops, prevents, or reduces the frequency, rate or extent of protein kinase B signaling, a series of reactions mediated by the intracellular serine/threonine kinase protein kinase B. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
negative regulation of AKT signaling [ER stress]
ER stress in hepatocytes induces PHLDA3 via IRE1-Xbp1s pathway, which facilitates liver injury by inhibiting Akt.
Unfolded protein is a subtype of substance with role. This entity participates in a unfolded protein response and plays a unfolded protein role.
Molecular complex is a subtype of onject aggregates. This entity has sub-parts of molecules.
Bip-stress sensor complex is a subtype of molecular complex. This entity has sub-parts of molecules, BIP/GRP78 and other molecule which has role of stress sensor. This entity is dependent on ER stress.
BIP-STRESS sensor complex (canonical)[ER stress]
Bip-PERK sensor complex is a subtype of molecular complex. This entity has sub-parts of molecules, BIP/GRP78 and PERK which has role of stress sensor. This entity is dependent on ER stress.
BIP-ATF6 complex is a subtype of molecular complex. This entity has sub-parts of molecules, BIP/GRP78 and ATF6 which has role of stress sensor. This entity is dependent on ER stress.
BIP-IRE1 complex is a subtype of molecular complex. This entity has sub-parts of molecules, BIP/GRP78 and IRE1 which has role of stress sensor. This entity is dependent on ER stress.
Hypofunction of mitochondrial fatty acid beta-oxidation is a subtype of hypofunction of fatty acid beta-oxidation: A process that performs a decreased or insufficient mitochondrial fatty acid beta-oxidation.
hypofunction of mitochondrial fatty acid beta-oxidation
Glutathione depletion is a subtype of depleting: A process that lessens markedly in the amount of glutathione. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Any process that activates or increases the frequency, rate or extent of cell death by apoptotic process. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
positive regulation of apoptotic process [ER stress]
In liver, the lesions observed in tunicamycin‐intoxicated animals include steatosis, bile ductular hyperplasia, swollen hepatocytes, and the presence of apoptotic bodies (Finnie and O'Shea 1989; Finnie and O'Shea 1990b; Finnie et al. 2004; Rutkowski et al. 2008).
Bip-unfolded protein is a subtype of a molecular complex. This entity has sub-parts of molecules: BIP/GRP78, and an unfolded protein.
A regulatory process that halts progression through the cell cycle during one of the normal phases (G1, S, G2, M). This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Because of the role of glutathione in cell cycle progression and apoptosis, an important role for CHAC1 in regulating the redox potential, proliferation, and viability of cells following ER stress is suggested. CHAC1 induction may induce a biphasic signal, first for cell cycle arrest, allowing the cell time to adapt to the stress, followed by apoptosis if the stress is insurmountable.
Forming disulfide bond is a subtype of binding: The interaction between molecules with interchain disulfide bonds. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
The endoplasmic reticulum sulfhydryl oxidase Ero1beta drives efficient oxidative protein folding with loose regulation.
Protein disulfide isomerase (PDI) is the first discovered, most abundant oxidoreductase in the ER. Depending on conditions, it catalyzes formation, isomerization, or reduction of disulfide bonds. Without oxidoreductase capacity in the ER, protein folding would be too slow and prone to disaster, with abundant aggregation and degradation favored. Considering that protein folding in principle is a spontaneous process and that chaperones guide the process, the formation of nonnative disulfide bonds during folding is a must.
Forming disulfide bond is a subtype of binding: The interaction between molecules with interchain disulfide bonds.
In chemistry, a disulfide refers to a functional group with the structure R−S−S−R′. The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. Occurrence in proteins Disulfide bonds play an important role in the folding and stability of some proteins, usually proteins secreted to the extracellular medium. Since most cellular compartments are reducing environments, in general, disulfide bonds are unstable in the cytosol, with some exceptions as noted below, unless a sulfhydryl oxidase is present. Disulfide bonds in proteins are formed between the thiol groups of cysteine residues by the process of oxidative folding. The other sulfur-containing amino acid, methionine, cannot form disulfide bonds. A disulfide bond is typically denoted by hyphenating the abbreviations for cysteine, e.g., when referring to ribonuclease A the "Cys26–Cys84 disulfide bond", or the "26–84 disulfide bond", or most simply as "C26–C84" where the disulfide bond is understood and does not need to be mentioned. The prototype of a protein disulfide bond is the two-amino-acid peptide cystine, which is composed of two cysteine amino acids joined by a disulfide bond (shown in Figure 3 in its unionized form). The structure of a disulfide bond can be described by its χss dihedral angle between the Cβ−Sγ−Sγ−Cβ atoms, which is usually close to ±90°.
PERK - signaling factor (canonical)[Perk-eIF2a signalling system]
Cell invasion into other cell is a subtype of moving A to the inside of B: A process of the movement of a cell into other different cells. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
cell invasion into other cell [Cell death]
Cell invasion into other cell is a subtype of moving A to the inside of B: A process of the movement of a cell into other different cells.
Negative regulation of tumor cell proliferation is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of tumor cell proliferation.
negative regulation of tumor cell proliferation
Negative regulation of tumor cell proliferation is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of tumor cell proliferation. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
negative regulation of tumor cell proliferation [Cell death]
A series of molecular signals mediated by ATF6 (activating transcription factor 6).
Any process that stops, prevents, or reduces the frequency, rate or extent of autophagy. Autophagy is the process in which cells digest parts of their own cytoplasm. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
negative regulation of autophagy [Cell death]
Metabolic dysfunction is a subtype of dysfunctioning: A process that performs an abnormal and incomplete metabolic function. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
Malfunctioning of metabolism is a subtype of malfunctioning process: A process that cannot perform a metabolism appropriately or cannot realize it at all.
Metabolic dysfunction is a subtype of dysfunctioning: A process that performs an abnormal and incomplete metabolic function.
Changing fatty acid homeostasis is a subtype of changing balance: A process that changes the steady state of fatty acid within an organism or cell.
Changing fatty acid homeostasis in peroxisome is a subtype of changing balance: A process that changes the steady state of fatty acid within peroxisomes.
changing fatty acid homeostasis in peroxisome
Changing fatty acid homeostasis in peroxisome is a subtype of lipid homeostasis imbalance: A process that changes the steady state of fatty acid within peroxisomes. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
changing fatty acid homeostasis in peroxisome [Eosinophilic granular degeneration]
Regulation of gene expression by p53 is a subtype of regulation of gene expression: A process that stops, prevents, or reduces the frequency, rate or extent of gene expression. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
regulation of gene expression by p53 [Cell death]
Regulation of gene expression by p53 is a subtype of regulation of gene expression: A process that stops, prevents, or reduces the frequency, rate or extent of gene expression.
The process of restoring DNA after damage. Genomes are subject to damage by chemical and physical agents in the environment (e.g. UV and ionizing radiations, chemical mutagens, fungal and bacterial toxins, etc.) and by free radicals or alkylating agents endogenously generated in metabolism. DNA is also damaged because of errors during its replication. A variety of different DNA repair pathways have been reported that include direct reversal, base excision repair, nucleotide excision repair, photoreactivation, bypass, double-strand break repair pathway, and mismatch repair pathway. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
Membrane phospholipid catabolic process is a subtype of lipid catabolic process: The chemical reactions resulting in the breakdown of membrane phopholipids This entity is a specific course-dependent process. This process can constitute the course of Cell death.
membrane phospholipid catabolic process [Cell death]
Pathogen proliferation is a subtype of increasing number of objects: A process becomes larger in the number of pathogen such as microorganism (bacteria, virus, mycoplasma, etc.) present in the body.
Pathogen proliferation is a subtype of increasing number of objects: A process becomes larger in the number of pathogen such as microorganism (bacteria, virus, mycoplasma, etc.) present in the body. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
Hyperfunction of immune response is a subtype of hyperfunctioning: A process that performs an excessive immune response. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
hyperfunction of immune response [Cell death]
Inflammatory response is a subtype of changing material: The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
A series of molecular signals mediated by the endoplasmic reticulum membrane stress sensor ATF6 (activating transcription factor 6). This pathway is a specific course-dependent and can constitute the course of ER stress.
ATF6-mediated unfolded protein response [ER stress]
A caspase-1-dependent cell death subroutine that is associated with the generation of pyrogenic mediators such as IL-1beta and IL-18. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
A series of molecular signals mediated by the endoplasmic reticulum membrane stress sensor PERK (PKR-like ER kinase). This pathway is a specific course-dependent and can constitute the course of ER stress.
PERK-mediated unfolded protein response [ER stress]
Decreasing proton motive force is a subtype of decreasing force: A process that changes the force of proton generated by electrochemical proton gradient to be lower. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
decreasing proton motive force [Mitochondrial disorder]
Hypofunction of fatty acid oxidation is a subtype of hypofunctioning of decomposing: A process that performs a decreased or insufficient fatty acid oxidation.
Anoikis is a subtype of cell death triggered by inadequate or inappropriate adherence to substrate e.g. after disruption of the interactions between normal epithelial cells and the extracellular matrix.
In response to several stimuli, neutrophils and eosinophils can release the so-called neutrophil extracellular traps (NETs), that is, microbicidal structures composed of nuclear chromatin, histones and granular antimicrobial proteins. Netotic cells exhibit massive vacuolization of the cytoplasm, rapid chromatin decondensation and breakdown of both the nuclear and granular membranes, which is required for proper NET formation. Netosis is insensitive to caspase inhibitors and necrostatin-1, further demonstrating that it constitutes a cell death subroutine distinct from apoptosis and regulated necrosis. Netosis might be defined as a cell death subroutine that is: (i) restricted to granulocytic cells; (ii) insensitive to (and perhaps dependent on)163 caspase inhibition; (iii) insensitive to necrostatin; (iv) dependent on NAPDH oxidase-mediated superoxide generation; and (v) dependent on (components of) the autophagic machinery https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252826/
The directed movement of the organic cation into hepatocyte vascular side (sinusoidal side) membrane during cholestasis. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
Lipophilic cationic drugs, estrogens, and lipids are exported by the canalicular multiple-drug resistance (MDR) P-glycoproteins, one of which is exclusive for phospholipids.
importing cation into hepatocyte vascular side (sinusoidal side) membrane [Cholestasis]
Collagenase inhibitor production is a subtype of protein production: A process that makes existent of a substance with collagenase inhibitor role due to biosynthesis or secretion resulting in an increase in its levels. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
collagenase inhibitor production [Fibrosis]
Collagenase inhibitor production is a subtype of protein production: A process that makes existent of a substance with collagenase inhibitor role due to biosynthesis or secretion resulting in an increase in its levels.
A role of combining with a signal and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity by catalysis of the reaction: ATP protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate.
transmembrane receptor protein serine/threonine kinase
A series of molecular signals mediated by IRE1 (Inositol-requiring transmembrane kinase/endonuclease).
Malfunctioning of electron transport coupled proton transport is a subtype of malfunctioning process: A process that cannot perform an electron transport coupled proton transport appropriately or cannot realize it at all.
PERK-eIF2a signaling is a subtype of PERK signaling (integrated pathway): Sequence of linked reactions, which has PERK-eIF2a signaling and gene regulation pathway. This pathway is dependent on the translation attenuation and can constitute the course of ER stress.
PERK-eIF2a signaling (integrated pathway)[ER stress - translation attenuation]
Fatty acid homeostasis imbalance in peroxisome is a subtype of changing balance: A process that becomes lacking afatty acid homeostastasis balance. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
fatty acid homeostasis imbalance in peroxisome [Eosinophilic granular degeneration]
Fatty acid homeostasis imbalance in peroxisome is a subtype of changing balance: A process that becomes lacking afatty acid homeostastasis balance. The degree is mild. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
fatty acid homeostasis imbalance in peroxisome (mild) [Eosinophilic granular degeneration]
Fatty acid homeostasis imbalance in peroxisome is a subtype of changing balance: A process that becomes lacking afatty acid homeostastasis balance. The degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
fatty acid homeostasis imbalance in peroxisome (moderate) [Eosinophilic granular degeneration]
The process of assisting in the disassembly of non-covalent linkages in a protein or protein aggregate, often where the proteins are in a non-functional or denatured state. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
PERK - signaling factor (canonical)[ER stress - translation attenuation]
The chemical reactions and pathways resulting in the formation of lipids, compounds soluble in an organic solvent but not, or sparingly, in an aqueous solvent. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. XBP-1-dependent UPR target genes: ERdj4, p58IPK, EDEM, RAMP-4, PDI-P5, and HEDJ, all of which appear to act in the ER and display Hsp40-like ATPase augmenting activity for the Hsp70 family chaperone proteins.
ERdj4 and ERdj5 are required for endoplasmic reticulum-associated protein degradation of misfolded surfactant protein C.
Genotoxic stress/p53-induced DNAJB9 inhibits the pro-apoptotic function of p53. DNAJB9 as an inducible gene of the tumor suppressor p53. DNAJB9 expression was induced by p53 or genotoxic stress in a p53-dependent manner, which was mediated by the Ras/Raf/ERK pathway. In addition, depletion of DNAJB9 by using siRNAs greatly increased genotoxic stress/p53-induced apoptosis, suggesting that DNAJB9 inhibits the pro-apoptotic function of p53.
XBP1(S) activates chaperone genes including DNAJB9, EDEM, RAMP4, p58IPK, and others. This results in an increase in protein folding activity in the ER.
This gene encodes a member of the mammalian activation transcription factor/cAMP responsive element-binding (CREB) protein family of transcription factors. This gene is induced by a variety of signals, including many of those encountered by cancer cells, and is involved in the complex process of cellular stress response. Multiple transcript variants encoding different isoforms have been found for this gene. It is possible that alternative splicing of this gene may be physiologically important in the regulation of target genes. [provided by RefSeq, Apr 2011]
stress induction ->ATF3 ->apotosis induction by activating pro-apoptic genesTNRSF1-B and BBC3 cancer development ->ATF3 ->apoptosis inhibition by repressing proapoptic genes CDKN1A Systems analysis of ATF3 in stress response and cancer reveals opposing effects on pro-apoptotic genes in p53 pathway. PMID:22046379 Stress-induced ATF3 binds to 40% of p53 targets and activates pro-apoptotic genes such as TNFRSF10B/DR5 and BBC3/PUMA. Cancer-associated ATF3, by contrast, represses these pro-apoptotic genes in addition to CDKN1A/p21. ATF3 has opposing, cell context-dependent effects on p53 target genes in DNA damage response and cancer development.
Opposing roles for calcineurin and ATF3 in squamous skin cancer. Calcineurin/NFAT inhibition counteracts p53-dependent cancer cell senescence, thereby increasing tumorigenic potential. ATF3, a member of the 'enlarged' AP1 family, is selectively induced by calcineurin/NFAT inhibition, both under experimental conditions and in clinically occurring tumors, and increased ATF3 expression accounts for suppression of p53-dependent senescence and enhanced tumorigenic potential.
Systems analysis of ATF3 in stress response and cancer reveals opposing effects on pro-apoptotic genes in p53 pathway.
Analysis of ATF3, a transcription factor induced by physiological stresses and modulated by gadd153/Chop10
Dysfunction of mitochondrial respiratory electron transport chain is a subtype of dysfunctioning: A process that performs an abnormal and incomplete functioning of respiratory electron transport chain.
dysfunction of mitochondrial respiratory electron transport chain
Hypofunction of mitochondrial fatty acid beta-oxidation is a subtype of hypofunction of fatty acid beta-oxidation: A process that performs a decreased or insufficient mitochondrial fatty acid beta-oxidation. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
hypofunction of mitochondrial fatty acid beta-oxidation [ER stress]
Lipid storage in liver is a subtype of lipid storage: The accumulation and maintenance in cells or tissues of lipids in the liver. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
The multiplication or reproduction of cells, resulting in the rapid expansion of a cell population. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
cell proliferation [Eosinophilic granular degeneration]
Receiving signal is a subtype of receiving: A process that recognizes another object and changes into a signal.
The process carried out by a cell that restores the biological activity of an unfolded or misfolded protein, using helper proteins such as chaperones. This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of ER stress (sustained) .
protein refolding (sustained) [ER stress]
Dissociation of IRE1:BIP heterodimer is a subtype of detaching: A process that disaggregates IRE-1-BIP heterodimers into BIP and IRE1. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Dissociation of IRE1:BIP Heterodimer [ER stress]
Protein refolding insufficiency is a subtype of malfunctioning process: A process that lacks performing the function of protein refolding required. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
protein refolding insufficiency [ER stress]
A role played by the entity within a toxicological context.
Pancreatic beta cell damage is a subtype of cellular damage: A process that injuries the structure of the pancreatic beta cell as the direct or indirect result of an external force.
Abnormal protein production is a subtype of protein production: A process that makes existent of an abnormal protein due to biosynthesis or secretion resulting in an increase in its levels.
A role played by the entity which inhibits or decreases the frequency, rate or extent of the glycosylation of one or more amino acid residues within a protein.
Accumulation of abnormal proteins in ER is a subtype of accumulation of abnormal proteins: A process that keeps abnormal protein(s) in the ER (endoplasmic reticulum).
Hypofunction of carbohydrate metabolism is a subtype of hypofunction of metabolism: A process that performs a decreased or insufficient carbohydrate metabolism. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
hypofunction of carbohydrate metabolism [ER stress]
Insulin resistance (process) is a subtype of decreasing sensitivity: A process that changes the sensitivity to the circulating insulin to be lower.
see quality : http://purl.obolibrary.org/obo/HP_0000855
Hypofunction of drug metabolism is a subtype of hypofunction of metabolism: A process that performs a decreased or insufficient drug metabolism.
Hypofunction of drug metabolism is a subtype of hypofunction of metabolism: A process that performs a decreased or insufficient drug metabolism. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
hypofunction of drug metabolism [ER stress]
Hypofunction of sequestering of calcium ion is a subtype of hypofunctioning: A process that performs a decreased or insufficient sequestering of calcium ion.
hypofunction of sequestering of calcium ion
A role played by a process to maintain homeostasis and to ptotect the toxic insult.
Hypofunction of sequestering of calcium ion is a subtype of hypofunctioning: A process that performs a decreased or insufficient sequestering of calcium ion. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
hypofunction of sequestering of calcium ion [ER stress]
Redox-assisted regulation of Ca2+ homeostasis in the endoplasmic reticulum by disulfide reductase ERdj5.
Hypofunction of lipid biosynthesis is a subtype of hypofunction of biosynthesis: A process that performs a decreased or insufficient lipid biosynthesis.
A role played by the entity which regulates the formation of lipids.
Malfunction of lipid biosynthesis is a subtype of malfunctioning: A process that cannot perform the lipid biosynthesis function appropriately or cannot realize it at all. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
malfunction of lipid biosynthesis [ER stress]
Malfunctioning of cellular membrane is a subtype of malfunctioning process: A process that cannot perform a cellular membrane function appropriately or cannot realize it at all.
Malfunctioning of cellular membrane is a subtype of malfunctioning process: A process that cannot perform a cellular membrane function appropriately or cannot realize it at all. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
malfunctioning of cellular membrane [ER stress]
A type of cell death that is morphologically characterized by an increasingly translucent cytoplasm, swelling of organelles, minor ultrastructural modifications of the nucleus (specifically, dilatation of the nuclear membrane and condensation of chromatin into small, irregular, circumscribed patches) and increased cell volume (oncosis), culminating in the disruption of the plasma membrane and subsequent loss of intracellular contents. Necrotic cells do not fragment into discrete corpses as their apoptotic counterparts do. Moreover, their nuclei remain intact and can aggregate and accumulate in necrotic tissues. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Insulin resistance (process) is a subtype of decreasing sensitivity: A process that changes the sensitivity to the circulating insulin to be lower. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
insulin resistance (process) [ER stress]
XBP1s Is an Anti-lipogenic Protein: XBP1s reduces hepatic lipogenic gene expression and improves hepatosteatosis in mouse models of obesity and insulin resistance, which leads us to conclude that XBP1s has anti-lipogenic properties in the liver.
Hepatic cirrhosis is a subtype of changing hardness: A process that changes the hardness of the liver to become hard due to the replacement of normal liver tissue to scar tissue.
Hepatic cirrhosis is a subtype of changing hardness: A process that changes the hardness of the liver to become hard due to the replacement of normal liver tissue to scar tissue. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
The chemical reactions and pathways resulting in the breakdown of misfolded proteins transported from the endoplasmic reticulum and targeted to cytoplasmic proteasomes for degradation. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
ER-associated misfolded protein catabolic process [ER stress]
The process carried out by a cell that restores the biological activity of an unfolded or misfolded protein, using helper proteins such as chaperones. This entity is a specific course-dependent process. This process can constitute the course of ER stress (early stage).
protein refolding [ER stress (early stage)]
Hypofunction of ATP biosynthesis is a subtype of hypofunction of biosynthesis: A process that performs a decreased or insufficient ATP biosynthesis. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
hypofunction of ATP biosynthesis [ER stress]
Increasing demand for protein refolding is a subtype of increasing functional demand: A process that changes the functional demand for protein refolding to be higher. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
increasing demand for protein refolding [ER stress]
Increasing demand for protein refolding is a subtype of increasing functional demand: A process that changes the functional demand for protein refolding to be higher.
Accumulation of compound in ER is a subtype of accumulation of xenobiotics: A process that keeps compound in the ER (endoplasmic reticulum).
Dissociation of PERK:BIP heterodimer is a subtype of detaching: A process that disaggregates PERK-BIP heterodimers into BIP and PERK. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Dissociation of PERK:BIP Heterodimer [ER stress]
CAD accumulation in lysosome is a subtype of compound accumulation in lysosome: A process that keeps CAD (Cationic Amphiphilic Drugs cationic amphiphile drug) in the lysosome. And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (moderate).
CAD accumulation in lysosome [Phospholipidosis (moderate) ]
The totality of all processes through which the phospholipidosis is realized.
Phospholipidosis is the appearance of intracellular accumulation of phospholipids and lamellar bodies, most likely from an impaired phospholipid metabolism of the lysosome. In drug induced phospholipidosis, CAD induces its own specific phospho-lipid composition and selectively targets organs.
Drug induced phospholipidosis: an acquired lysosomal storage disorder. Biochim Biophys Acta. 2013, 1831(3):602-11.
A process that changes the activity of the NRF2 to be higher. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
A process that stops, prevents, or reduces the frequency, rate or extent of phospholipid degradation severely. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
negative regulation of phospholipid degradation [Phospholipidosis (severe) ]
Negative regulation of phospholipase transcription is a subtype of negative regulation of transcription, DNA-templated: A process that stops, prevents, or reduces the frequency, rate or extent of phospholipase transcription.
negative regulation of phospholipase transcription
Hypofunction of phospholipase gene expression is a subtype of hypofunction of phospholipase gene expression: A process that performs a decreased or insufficient phospholipase gene expression. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
hypofunction of phospholipase gene expression [Phospholipidosis (severe) ]
Lysosomal dysfunction is a subtype of dysfunctioning: A process that performs an abnormal and incomplete lysosomal function. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
lysosomal dysfunction [Phospholipidosis (severe) ]
Lysosomal dysfunction is a subtype of dysfunctioning: A process that performs an abnormal and incomplete lysosomal function.
Malfunctioning of cellular membrane is a subtype of malfunctioning process: A process that cannot perform a cellular membrane function appropriately or cannot realize it at all. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
malfunctioning of cellular membrane [Phospholipidosis (severe) ]
Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of phospholipids. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
positive regulation of phospholipid biosynthetic process [Phospholipidosis (severe) ]
glutathione synthetic gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) involved in glutathione synthesis.
Phospholipid material transport is a subtype of molecule transport: A process that of the directed movement of phospholipid materials into a peroxisome.
Hyperfunction of phospholipid material transport is a subtype of hyperfunction of transport: A process that performs an excesssive phospholipid material transport. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
hyperfunction of phospholipid material transport [Phospholipidosis (severe) ]
Increase in intracellular calcium level is a subtype of increase in calcium level: A process that changes the calcium ion concentration within a cell to be higher. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
increase in intracellular calcium level [Phospholipidosis]
In the imbalance model, the basic units are as follows: 1) a functioning process (supply) for biological defense and maintaining homeostasis; 2) a functional demand process (demand) as toxic activity; 3) balance/imbalance between toxic activity and defense processes; and 4) outcome from organelles, cells, or tissues to the organ exhibiting toxicity manifestations. This entity is a compound state that inculdes step 1 to 4. The defense performance level and the functional demand level are low, as a result, keeping the balance. This state reflects the adaptation in the body.
toxicological balance L=L (maintining homeostasis at lower level)
Increasing uptake amount of mitochondrial calcium ion is a subtype of increasing quantity: A process that changes the uptake amount of mitochondrial calcium ion to be higher.
increasing uptake amount of mitochondrial calcium ion
Hypofunction of ATP biosynthesis is a subtype of hypofunction of biosynthesis: A process that performs a decreased or insufficient ATP biosynthesis. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
hypofunction of ATP biosynthesis [Mitochondrial disorder]
Mitochondria-targeted cyclin B1/Cdk1 increases mitochondrial respiration with enhanced oxygen consumption and ATP generation, which provides cells with efficient bioenergy for G2/M transition and shortens overall cell-cycle time. As expected, in vivo phosphorylation of each subunit at G2/M phase was inhibited in cells transfected with Cdk1 siRNA (Figure 4C, lane 3), which arrested cells at the G2/M phase (Figure S5).
High-level exposures may result in increased fission, which blocks efficient ATP generation and limits rates of functional complementation, in addition to potentially leading to apoptosis.
Supporting this notion, PCK1 expression in SK-Hep-1 dramatically reduced cellular ATP level by 4 folds in cells cultured in low glucose medium, but not in normal medium (Fig. 4c). In addition, supplement of dimethyl-α-KG may also increase cellular ATP level and alleviate energy stress, as indicated by the decreased phosphorylation of AMPKα1 and ACC (Fig. 5f).
Mitochondrial-derived ROS also activate AMP-activated protein kinase (AMPK) secondary to redox changes and mitochondrial ATP production.
Accumulating evidence has shown that defective hepatic mitochondrial respiration characterized by damaged mitochondria accumulation can impair mitochondrial fatty acid β-oxidation, which sequentially causes various adverse consequences, such as excessive ROS, reduced ATP production, and hepatic fatty acid accumulation.
The directed movement of calcium from the lysosome.
Increasing uptake amount of mitochondrial calcium ion is a subtype of increasing quantity: A process that changes the uptake amount of mitochondrial calcium ion to be higher. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
increasing uptake amount of mitochondrial calcium ion [Phospholipidosis]
Decreasing mitochondrial membrane potential is a subtype of decreasing membrane potential: A process that changes the electrical potential of a mitochondrial membrane to be lower. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
decreasing mitochondrial membrane potential [Phospholipidosis]
Hypofunction of ATP biosynthesis is a subtype of hypofunction of biosynthesis: A process that performs a decreased or insufficient ATP biosynthesis. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
hypofunction of ATP biosynthesis [Phospholipidosis]
Autolysis is a subtype of dissolving: The disintegration of a cell by rupture of the cell membrane by the action of their own enzymes.
Stabilizing membrane structure is a subtype of keeping structure: A process that maintains the membrane structure.
Stabilizing lysosomal membrane structure is a subtype of stabilizing membrane structure: A process that maintains the membrane structure in the lysosome.
stabilizing lysosomal membrane structure
Stabilizing lysosomal membrane structure is a subtype of stabilizing membrane structure: A process that maintains the membrane structure in the lysosome. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
stabilizing lysosomal membrane structure [Phospholipidosis]
Attenuation of the lysosomal death pathway by lysosomal cholesterol accumulation.
Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense) .
Negative regulation of apoptotic process might be a defense process prevent the number of cells from decreasing too much.
negative regulation of apoptotic process [Phospholipidosis (excessive defense) ]
The directed movement of calcium from the lysosome. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
release of calcium ion from lysosome [Phospholipidosis]
Lysosomal Re-acidification Prevents Lysosphingolipid-Induced Lysosomal Impairment and Cellular Toxicity: Neutralization can cause release of lysosomal Ca2+ and cathepsins: Ca2+ release could compromise cytoskeletal function and hence cell division, whereas cathepsin release and activation could initiate cell death. In addition, increasing lysosomal pH would be predicted to decrease function of any lysosomal enzymes evolutionarily optimized for function in an acidic environment.
Obesity is a subtype of increasing weight: A process that changes the body weight to be higher. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
Negative regulation of inflammatory response is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of inflammatory response. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
negative regulation of inflammatory response [Phospholipidosis]
Negative regulation of inflammatory response is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of inflammatory response.
negative regulation of inflammatory response
Angiogenin is up-regulated in the nucleus and cytoplasm in human primary breast carcinoma and is associated with markers of hypoxia but not survival.
Angiogenin secretion from hepatoma cells activates hepatic stellate cells to amplify a self-sustained cycle promoting liver cancer.
Tumor growth is a subtype of cell growth: The process in which a tumor cell increases in size. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
A role played by the entity involved in DNA repair processes including direct reversal, base excision repair, nucleotide excision repair, photoreactivation, bypass, double-strand break repair pathway, and mismatch repair pathway.
A role played by the entity which involves in regulating a cell cycle process.
Increasing phospholipid metabolite is a subtype of increasing quantity: A process that changes the amount of phospholipid metabolites to be larger.
Gadd45a - cell cycle arrest factor (rat)[Phospholipidosis]
The GADD45 inhibition of Cdc2 kinase correlates with GADD45-mediated growth suppression.
Gadd45 may participate in the coupling between chromatin assembly and DNA repair.
NF-kappa B-mediated repression of growth arrest- and DNA-damage-inducible proteins 45alpha and gamma is essential for cancer cell survival.
Gadd45 in stress signaling, cell cycle control, and apoptosis.
Any substance that inhibits the process of fibrosis.
Gadd45a - fibrosis inhibitor (rat)[Phospholipidosis]
New role and molecular mechanism of Gadd45a in hepatic ﬁbrosis: Significant downregulation of Gadd45a, but not Gadd45b or Gadd45g, accompanied by activation of the TGF-beta (Smad) signaling pathways was detected in fibrotic liver tissues of mice and isolated HSCs with chronic liver injury induced by CCl4 treatment. Gadd45a may exert a protective effect against hepatic ﬁbrosis induced by CCl4, via the inhibition of canonical transforming growth factor-beta (Smad) signaling and ﬁbrogenic gene expression.
Decreasing CAD in lysosomal membranes is a subtype of decreasing quantity: A process that changes the quantity of the Cationic Amphiphilic Drugs (CAD) in lysosomal membranes to be smaller. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
decreasing CAD in lysosomal membranes [Phospholipidosis]
Decreasing CAD in lysosomal membranes is a subtype of decreasing quantity: A process that changes the quantity of the Cationic Amphiphilic Drugs (CAD) in lysosomal membranes to be smaller.
glutathione synthetic gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) involved in glutathione synthesis. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
glutathione synthetic gene expression [Glutathione depletion]
Any process that increases the rate, frequency, or extent of phospholipid catabolism, the chemical reactions and pathways resulting in the breakdown of phospholipids, any lipid containing phosphoric acid as a mono- or diester. This entity is a specific course-dependent process. This process can constitute the course of phospholipidosis.
positive regulation of phospholipid catabolic process [phopholipidosis - normal]
Hyperfunction of phospholipase gene expression is a subtype of hyperfunction of gene expression: A process that performs an excesssive phospholipase gene expression.
hyperfunction of phospholipase gene expression
Hyperfunction of phospholipase gene expression is a subtype of hyperfunction of gene expression: A process that performs an excesssive phospholipase gene expression. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
hyperfunction of phospholipase gene expression [Phospholipidosis]
Keeping acidic environment in lysosome is a subtype of keeping quality: A process that maintains the acidic environment within the interior of the lysosomes. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
keeping acidic environment in lysosome [Phospholipidosis]
Keeping acidic environment in lysosome is a subtype of keeping quality: A process that maintains the acidic environment within the interior of the lysosomes.
A role played by the entity which positively regulates the process of tumor cell growth.
A role played by the entity within a pharmacological context.
Increasing number of macrophage derived foam cell (niemann pick cell) is a subtype of increasing number of objects: A process that becomes larger in the number of foam cell, a type of macrophage (niemann pick cell) containing lipids in small vacuoles, in the liver. This entity is a specific course-dependent process. This process can constitute the course of Niemann Pick Disease Type A/ B.
increasing number of macrophage derived foam cell (niemann pick cell) [Niemann Pick Disease Type A/ B]
Hepatic cirrhosis is a subtype of changing hardness: A process that changes the hardness of the liver to become hard due to the replacement of normal liver tissue to scar tissue. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense).
hepatic cirrhosis [Phospholipidosis (excessive defense)]
Inflammatory cytokine gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature inflammatory cytokine gene product or products (proteins or RNA). This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
inflammatory cytokine gene expression [Phospholipidosis]
Inflammatory cytokine gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature inflammatory cytokine gene product or products (proteins or RNA).
interleukin 2 receptor, beta - apotosis restricting factor [Phospholipidosis]
IL2RB - apotosis inhibitor (human)[Phospholipidosis]
New role for Shc in activation of the phosphatidylinositol 3-kinase/Akt pathway.
interleukin 2 receptor, beta - cell cycle progression promoting factor [Phospholipidosis]
IL2RB - cell cycle progression promoting factor (human)[Phospholipidosis]
Biochem Biophys Res Commun. 2002 Aug 30;296(4):929-36. IL-2 receptor signaling through the Shb adapter protein in T and NK cells. Interleukin-2 induces heterodimerization of the IL-2 receptor beta and gamma subunits. The IL-2Rbeta and gamma chains were found to co-immunoprecipitate with Shb, when each alone was co-expressed with Shb in COS cells. Using fusion proteins, the Shb SH2 domain was found to associate in a phosphotyrosine-dependent manner with the IL-2 receptor beta and gamma subunits upon IL-2 stimulation in primary T cells and the NK cell line NK-92. JAK1 and JAK3 were also found to associate with Shb, but in contrast to the Shb-IL-2 receptor association, JAK1 and 3 appear to associate with the proline-rich regions of Shb. In conclusion, Shb links the IL-2 receptor to other signaling proteins and mediates the regulation of apoptosis in the presence of IL-2.
Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3627-32. Transduction of interleukin-2 antiapoptotic and proliferative signals via Akt protein kinase. The interleukin-2 (IL-2) receptor (IL-2R) is composed of three subunits. Of these, IL-2Ra is required for high-affinity IL-2 binding, while IL-2R beta and IL-2R gamma(c) are required for the transduction of IL-2-generated signals. Signals transduced via the S region of the IL-2R beta (amino acids 267-322) in BAF/3 cells activate the phosphatidylinositol 3-kinase (PI3-kinase) and induce the expression of Bcl-2 and c-myc. Through the induction of Bcl-2, IL-2 inhibits apoptosis and through the combination of Bcl-2 and c-myc it stimulates progression through the cell cycle. Akt activation by IL-2 depends on PI3-kinase signals transduced via the S region of the IL-2R beta and is linked to the translocation of Akt to the cell membrane. Expression of catalytically active Akt mutants in BAF/3 cells expressing IL-2R beta[A0]delta S promotes the expression of Bcl-2 and c-myc, inhibits apoptosis induced by IL-3 deprivation or staurosporine, and stimulates cell cycle progression. The same mutants also stimulate cell cycle progression in 2780a, an IL-2-dependent T cell line that undergoes G1 arrest rather than apoptosis after IL-2 deprivation. The activation of Akt by IL-2 via the PI3-kinase and the rescue of the PI3-kinase-mediated antiapoptotic and proliferative IL-2 signals by catalytically active Akt indicate that these signals are transduced by Akt.
A role played by the entity that positively regulates the process of cell cycle.
A role played by the entity that positively regulates the process of cell cycle arrest.
positive regulator of cell cycle arrest role
A role played by the entity which positively regulates the process of cell proliferation.
positive regulator of cell proliferation
A role played by the entity which positively regulates the process of tumor cell proliferation.
positive regulator of tumor cell proliferation
Any process involved in the maintenance of an internal steady state of phospholipid within an organism or cell. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (latent).
maintaining phospholipid homeostasis [Phospholipidosis (latent)]
Hyperfunction of biological defense function is a subtype of hyperfunction of defensive function: A process that performs an excessive biological defensive function.
hyperfunction of biological defense function
Hyperfunction of cell survival is a subtype of hyperfunctioning: A process that performs an excesssive cell survival.
Hyperfunction of cell survival is a subtype of hyperfunctioning: A process that performs an excesssive cell survival. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense).
hyperfunction of cell survival [Phospholipidosis (excessive defense)]
Hyperfunction of biological defense function is a subtype of hyperfunction of defensive function: A process that performs an excessive biological defensive function. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense).
hyperfunction of biological defense function [Phospholipidosis (excessive defense)]
Hyperfunction of removing is a subtype of hyperfunctioning: A process that performs an excessive removal function. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense).
hyperfunction of removing [Phospholipidosis (excessive defense)]
Hyperfunction of removing is a subtype of hyperfunctioning: A process that performs an excessive removal function.
AKT - apotosis inhibitor (canonical)[Phospholipidosis]
A pathologic process that involves the transformation of normal cells to a neoplastic state. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense).
carcinogenesis [Phospholipidosis (excessive defense)]
Converting type is a subtype of changing an operand: A process that changes the type, kind, or class of the operand.
Catalysis role of the hydrolysis of a lipid or phospholipid.
A role played by an entity that responds to immunity.
Glutathione depletion dependent gene is a subtype of toxic course dependent chemical entity. This gene can participate in the course of glutathione depletion as a gene product. Gene profile:Mice
glutathione depletion dependent gene [mouse]
A role played by the entity that ipositive regulates the cytokine production.
A role played by the entity that ipositive regulates the IL-2 production.
A role played by the entity which inhibits the process of infmammatory response.
PLA2G5 - anntiinflammation factor (human)[Phospholipidosis]
Catalysis of the reaction: ATP + a protein tyrosine = ADP + protein tyrosine phosphate.
Phospholipid metabolism balance is a subtype of maintaining balance: A process that keeps a balance of phospholipid metabolism. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (latent).
phospholipid metabolism balance [Phospholipidosis (latent) ]
This gene encodes a 105 kD protein which can undergo cotranslational processing by the 26S proteasome to produce a 50 kD protein. The 105 kD protein is a Rel protein-specific transcription inhibitor and the 50 kD protein is a DNA binding subunit of the NF-kappa-B (NFKB) protein complex. NFKB is a transcription regulator that is activated by various intra- and extra-cellular stimuli such as cytokines, oxidant-free radicals, ultraviolet irradiation, and bacterial or viral products. Activated NFKB translocates into the nucleus and stimulates the expression of genes involved in a wide variety of biological functions. Inappropriate activation of NFKB has been associated with a number of inflammatory diseases while persistent inhibition of NFKB leads to inappropriate immune cell development or delayed cell growth. Alternative splicing results in multiple transcript variants encoding different isoforms, at least one of which is proteolytically processed. [provided by RefSeq, Feb 2016]
The Nuclear Factor NF-κB Pathway in InflammationThe nuclear factor NF-kappaB pathway in inflammation.
Hypofunction of phospholipase gene expression is a subtype of hypofunction of transcription, DNA-templated: A process that performs a decreased or insufficient phospholipase gene expression.
decreasing function of phospholipase transcription, DNA-templated
hypofunction of phospholipase gene expression
Any process that stops, prevents, or reduces the frequency, rate or extent of endocytosis. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
negative regulation of endocytosis [Phospholipidosis (severe) ]
Catalysis role of the reaction: ATP + creatine = N-phosphocreatine + ADP + 2 H(+).
In both mammals and birds, the creatine kinase (CK) family consists of four types of genes: cytosolic brain type (B-CK); cytosolic muscle type (M-CK); mitochondrial ubiquitous, acidic type (Mia-CK); and mitochondrial sarcomeric, basic type (Mib-CK).
Increasing demand for response to mitochondrial oxidative stress is a subtype of increasing demand for response to oxidative stress: A process that changes the functional demand for the response to the mitochondrial oxidative stress to be higher.
increasing demand for response to mitochondrial oxidative stress
Glutathione conjugation (supply) - function demand imbalance is a subtype of imbalance: A process that becomes lacking a homeostastasis balance between glutathione conjugation supply and demand.
Glutathione conjugation (supply) - function demand imbalance
Hyperfunction of biological repair function is a subtype of hyperfunctioning: A process that performs an excessive biological repair function.
hyperfunction of biological repair function
Hypofunction of xenobiotics conjugate excretion is a subtype of hypofunction of liver's excretion: A process that performs a decreased or insufficient xenobiotics conjugate excretion.
hypofunction of xenobiotics conjugate excretion
Decreasing excretion quantity of bile acid is a subtype of decreasing quantity: A process that changes the excretion quantity of of bile acids to be lower.
decreasing excretion quantity of the bile acid
Catalysis of the transfer of acyl groups from an acyl-CoA to lysophosphatidic acid to form phosphatidic acid.
Lysophosphatidic acid (LPA) acyltransferase (LPAAT), also known as 1-acyl sn-glycerol-3-phosphate acyltransferase (1-AGPAT) (EC 2.3.1.51), catalyzes the conversion of LPA to phosphatidic acid (PA).
Catalysis role of the reaction: triacylglycerol + H2O = diacylglycerol + a carboxylate.
triacylglycerol ester hydrolase activity
Phospholipid metabolism imbalance is a subtype of imbalance: A process that becomes lacking a homeostastasis balance of phospholipid metabolism.
Constitutive androstane receptor activation by phenobarbital is a subtype of activating nuclear receptor: A process that changes the activity of the activating CAR ( constitutive androstane receptor) with a nuclear receptor role to be higher by phenobarbital. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
activating CAR [Ground glass degeneration]
constitutive androstane receptor activation by phenobarbital [Ground glass appearance]
In vitro CAR-RXR heterodimer bound to the ER6 responsive element of the human CYP3A4 gene and mediated PB-dependent expression in a stable HepG2 cell line.
Dysfunction of glycerophospholipid degradation is a subtype of dysfunction of phospholipid degradation: A process that performs an abnormal and incomplete glycerophospholipid degradation.
dysfunction of glycerophospholipid degradation
Hyperfunction of increasing the amount of phenobarbital is a process of performing an excessive function of increasing the amount of drugs. This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (sustained) .
hyperfunction of increasing the amount of phenobarbital (sustained) [Ground glass appearance]
Dysfunction ofphosphatidylinositol degradation is a subtype of dysfunction of glycerophospholipid degradation: A process that performs an abnormal and incomplete phosphatidylinositol degradation.
dysfunction ofphosphatidylinositol degradation
Dysfunction of phosphatidylethanolamine degradation is a subtype of dysfunction of glycerophospholipid degradation: A process that performs an abnormal and incomplete phosphatidylethanolamine degradation.
dysfunction of phosphatidylethanolamine degradation
Dysfunction of phosphatidylglycerol degradation is a subtype of dysfunction of glycerophospholipid degradation: A process that performs an abnormal and incomplete phosphatidylglycerol degradation.
dysfunction of phosphatidylglycerol degradation
Dysfunction of phosphatidylcholine degradation is a subtype of dysfunction of glycerophospholipid degradation: A process that performs an abnormal and incomplete phosphatidylcholine degradation.
dysfunction of phosphatidylcholine degradation
Dysfunction of phosphatidyl-L-serine degradation is a subtype of dysfunction of glycerophospholipid degradation: A process that performs an abnormal and incomplete phosphatidyl-L-serine degradation.
dysfunction of phosphatidyl-L-serine degradation
Dysfunction of phosphatidic acid degradation is a subtype of dysfunction of glycerophospholipid degradation: A process that performs an abnormal and incomplete phosphatidic acid degradation.
dysfunction of phosphatidic acid degradation
Hyperfunction of cell proliferation is a subtype of hyperfunction of increasing number: A process that performs an excessive cell proliferation.
A pathologic process that involves the transformation of normal cells to a neoplastic state. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
carcinogenesis [Ground glass appearance]
A single dose of N-nitrosomorpholine by daily treatments with phenobarbital for 12M in rats initiates and promotes neoplastic transformation in the liver. Phenobarbital is representive of a large number of compounds that appear to promote liver tumor formation in mice
A process that results in an increase in hepatic cell number by cell division, often leading to an increase in the size of an liver. This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (sustained) .
hepatocyte proliferation (sustained) [Ground glass appearance]
In mice and rats phenobarbital and related compounds only cause liver tumors at doses that cause liver enlargement due to an increase in cell number (hepatocyte hyperplasia) and cell size (hepatocellular hypertrophy).
Hyperfunction of hepatocyte proliferation is a subtype of hyperfunction of cell proliferation: The multiplication or reproduction of hepatocytes, resulting in the expansion of a cell population. Hepatocytes form the main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules.
hyperfunction of hepatocyte proliferation
Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process. This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (sustained) .
negative regulation of apoptotic process (sustained) [Ground glass appearance]
Any process that stops, prevents, or reduces the frequency, rate or extent of autophagy. Autophagy is the process in which cells digest parts of their own cytoplasm. This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (sustained) .
negative regulation of autophagy (sustained) [Ground glass appearance]
Phospholipid metabolism imbalance is a subtype of imbalance: A process that becomes lacking a homeostastasis balance of phospholipid metabolism. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
phospholipid metabolism imbalance [Phospholipidosis]
Accumulation of drug in hepatocyte is a subtype of accumulation of xenobiotics: A process that keeps compound in the hepatocyte.
Increasing demand for NAPQI metabolism is a subtype of increasing functional demand: A process changes the functional demand for the for NAPQI metabolism to be higher.
In the imbalance model, the basic units are as follows: 1) a functioning process (supply) for biological defense and maintaining homeostasis; 2) a functional demand process (demand) as toxic activity; 3) balance/imbalance between toxic activity and defense processes; and 4) outcome from organelles, cells, or tissues to the organ exhibiting toxicity manifestations. This entity is a compound state that inculdes step 1 to 4. The defense performance level is very low (L) than the moderate (M) in normal condition. Threfore even if the functional demand level is Moderatelevel (M) in the daily life in the helathy person, which leads to the imbalance and leads to toxicity manifestation.
The totality of all processes through which hepatic fibrosis is realized.
Hypofunction of drug metabolism phase II is a subtype of hypofunction of drug metabolism: A process that performs a decreased or insufficient drug metabolism phase II.
hypofunction of drug metabolism phase II
glutamate-cysteine ligase modifier subunit
Hyperfunction of drug metabolizing enzyme gene expression is a subtype of hyperfunction of gene expression: A process that performs an excesssive drug metabolizing enzyme gene expression.
hyperfunction of drug metabolizing enzyme gene expression
Increasing number of dead cells in liver is a subtype of cell proliferation: A process that becomes larger in the number of dead cells in the liver. This entity is a specific course-dependent process. This process can constitute the course of Oxidative stress.
increasing number of dead cells in liver [Oxidative stress]
Cel cycle related gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature cell cycle related gene product or products (proteins or RNA).
Hyperfunction of fatty acid biosynthesis is a subtype of hyperfunction of biosynthesis: A process that performs an excessive fatty acid biosynthesis.
hyperfunction of fatty acid biosynthesis
Lipid metabolism imbalance is a subtype of imbalance: A process that becomes lacking a homeostastasis balance of lipid metabolism.
Hyperfunction of lipid biosynthesis is a subtype of hyperfunction of biosynthesis: A process that performs an excessive lipid biosynthesis.
Hyperfunction of lipid synthetic gene expression is a subtype of hyperfunction of gene expression: A process that performs an excesssive lipid biosynthetic gene expression.
hyperfunction of lipid synthetic gene expression
Lipid vacuole organization is a subtype of vacuole organization: A process that s carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a lipid vacuole.
Liver carcinogenesis dependent process is a subtype of toxic course dependent process: A process that can constitute the course of liver carcinogenesis.
Leaking proton ion is a subtype of leaking: A process that leaks the proton from the mitochondria.
Negative regulation of respiratory electron transport chain is a subtype of negative regulation process: Any process that stops, prevents or reduces the frequency, rate or extent of mrespiratory electron transport chain.
negative regulation of respiratory electron transport chain
Changing iron ion concentration is a subtype of changing concentration: A process that changes the iron (Fe) concentration in the blood to be lower.
Hyperfunction of mitochondrial fatty acid beta-oxidation is a subtype of hyperfunction of fatty acid beta-oxidation: A process that performs an excessive mitochondrial fatty acid beta-oxidation.
hyperfunction of mitochondrial fatty acid beta-oxidation
Hyperfunction of gene expression is a subtype of hyperfunctioning: A process that performs an excesssive gene expression.
Hyperfunction of biosynthesis is a subtype of hyperfunctioning: A process that performs an excessive biosynthesis.
Hyperfunction of drug metabolism is a subtype of hyperfunctioning of metabolism: A process that performs an excessive drug metabolism.
Decreasing bile flow in bile canaliculus is a subtype of decreasing bile flow: A process that changes the amount of bile flow in bile canaliculus to be lower.
decreasing bile flow in bile canaliculus
Hyperfunction of decompoing is a subtype of hyperfunctioning: A process that performs an excessive decomposition.
A role played by the entity for peroxisome proliferation
Hyperfunction of transport is a subtype of hyperfunctioning: A process that performs an excesssive transport.
Hyperfunction of metabolism is a subtype of hyperfunctioning: A process that performs an excessive metabolism.
A role played by the entity that activates or increases the frequency, rate or extent of feeding behavior.
positive regulator role of feeding behavior
Hypofunction of metabolism is a subtype of hypofunction of changing between operands: A process that performs a decreased or insufficient metabolism.
Hypofunction of removing is a subtype of hypofunctioning: A process that performs a decreased or insufficient removing.
Hypofunction of transcription, DNA-templated is a subtype of hypofunctioning: A process that hypofunction of transcription, DNA-templated
decreasing function of transcription, DNA-templated
hypofunction of transcription, DNA-templated
PPARalpha inactivation is a subtype of inactivation: A process that changes the activity of the activating PPAR alpha (Peroxisome Proliferator Activated Receptor Alpha) with a nuclear receptor role to be lower. This entity is a specific course-dependent process. This process can constitute the course of alcoholic fatty liver.
PPARalpha inactivation [alcoholic fatty liver]
A role played by the entity which regulates lipid metabolic process.
Hyperfunction of moving drug to the inside of liver is a subtype of hyperfunction of moving A to the inside of B: A process that performs an excesssive moving drug to the inside of liver.
hyperfunction of moving drug to the inside of liver
Hyperfunction of defensive function is a subtype of hyperfunctioning: A process that performs an excessive defensive function.
Mitochondrial dysfunction is a subtype of dysfunctioning: A process that performs an abnormal and incomplete mitochondrial function.
A role played by the entity which positively regulates the formation of phospholipids.
phospholipid biosynthetic positive regulator role
Cell survial is a subtype of keeong quantity: A process that keeps the viability of a cell. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
Increasing drug metabolite is a subtype of increasing quantity: A process that changes the amount of drug metabolites to be higher.
Dissociation of Nrf2-Keap1 complex is a subtype of detaching: A process that disaggregates a Nrf2-Keap1 complexe into Nrf2 and Keap1. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
dissociation of Nrf2-Keap1 complex [Glutathione depletion]
Activation of thioredoxin pathway is a subtype of activating: A process that changes the activity of the thioredoxin pathway to be higher. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
activation of thioredoxin pathway [Glutathione depletion]
Under GSH deprivation, the cytosolic thioredoxin/thioredoxin reductase system plays an essential role for the cells to deal with the excess amount of intracellular cystine.
Hyperfunction of anti-oxidative stress is a subtype of hyperfunctioning: A process that performs an excesssive response to oxidative stress. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
hyperfunction of anti-oxidative stress [Glutathione depletion]
P53 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by p53. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
p53 signaling (primitive) [Glutathione depletion]
Caspase signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the caspase. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
caspase signaling (primitive) [Glutathione depletion]
A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
apoptotic process [Glutathione depletion]
Cell Death and Differentiation (2009) 16, 1303–1314; Apoptosis and glutathione: beyond an antioxidant Glutathione (GSH) depletion is a common feature of apoptotic cell death triggered by a wide variety of stimuli including activation of death receptors, stress, environmental agents, and cytotoxic drugs. Although initial studies suggested that GSH depletion was only a byproduct of oxidative stress generated during cell death, recent discoveries suggest that GSH depletion and post-translational modifications of proteins through glutathionylation are critical regulators of apoptosis. GSH is essential for cell survival as the GSH-depleted knock-out mouse of γ-GCS dies from massive apoptotic cell death. As the availability of cysteine is the rate-limiting factor in GSH formation, cysteine starvation has been shown to induce apoptosis by GSH depletion.
Increasing number of dead cells in liver is a subtype of cell proliferation: A process that becomes larger in the number of dead cells in the liver. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
increasing number of dead cells in liver [Glutathione depletion]
Liver dysfunction is a subtype of dysfunctioning: A process that performs an abnormal and incomplete liver function. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
liver dysfunction [Glutathione depletion]
A role played by the entity that activates the activity of cytochrome P450 involved in catalysis of organic substances.
JNK signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the JNK (a stress-activated protein kinase (SAPK) ). This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
JNK signaling (primitive) [Glutathione depletion]
APAP-induced liver injury involves JNK activation, due to increased reactive oxygen species generated by GSH-depleted mitochondria, and translocation of activated JNK to mitochondria where JNK induces mitochondrial permeability transition and inhibits mitochondria bioenergetics.
Any process that modulates the rate or extent of progression through the cell cycle. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
regulation of cell cycle [Glutathione depletion]
Keap1 oxidative modification by electrophiles is a subtype of protein binding: Interacting between a protein and electrophiles. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
Keap1 oxidative modification by electrophiles
A process that changes the activity of the eIF2a by PERK. This process is dependent on the PERK-eIF2A pathway and can constitute the course of ER stress.
changing activity of eIF2a by PERK [ER stress PERK - eIF2A pathway]
A metabolic process that generates a pool of NADPH by the reduction of NADP+. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
NADPH regeneration [Glutathione depletion]
Nat Rev Drug Discov. 2013 Dec;12(12):931-47. doi: 10.1038/nrd4002. Modulation of oxidative stress as an anticancer strategy. Both GSH and TXN utilize NADPH to regenerate themselves once they have reduced reactive oxygen species (ROS). These are all upregulated by NRF2.
Keap1 inactivation is a subtype of molecular inactivation: A process that changes the activity of the Keap1 to be lower.
Abnormality of membrane is a subtype of changing abnormal cellular structure: A process that changes the membrane stucture abnormally. The degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
abnormality of membrane (severe) [Cell death]
TP53 - cell cycle regulation factor (canonical)[Cell death]
Eosinogranular degeneration dependent chemical compound is a subtype of toxic course dependent chemical entity. This entity (drug) can participate in the course of eosinogranular degeneration.
eosinogranular degeneration dependent chemical compound
Chaperon production is a subtype of protein production: A process that makes existent of a protein with a chaperon role due to biosynthesis or secretion resulting in an increase in its levels. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Generating a chparon protein is a generating process to make a protein as an output in the course of ER stress.
Heat Shock Protein Family A (Hsp70) Member 5 [ER stress]
ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of Golgi localization signals.
Localization of the gene encoding human BiP/GRP78, the endoplasmic reticulum cognate of the HSP70 family, to chromosome 9q34. Genomics 20: 281-284, 1994. BiP/GRP78 is a member of the HSP70 family involved in the folding and assembly of proteins in the endoplasmic reticulum.
A type of cell death that is morphologically characterized by an increasingly translucent cytoplasm, swelling of organelles, minor ultrastructural modifications of the nucleus (specifically, dilatation of the nuclear membrane and condensation of chromatin into small, irregular, circumscribed patches) and increased cell volume (oncosis), culminating in the disruption of the plasma membrane and subsequent loss of intracellular contents. Necrotic cells do not fragment into discrete corpses as their apoptotic counterparts do. Moreover, their nuclei remain intact and can aggregate and accumulate in necrotic tissues. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
The cleavage of DNA during apoptosis, which usually occurs in two stages: cleavage into fragments of about 50 kbp followed by cleavage between nucleosomes to yield 200 bp fragments. This entity is a specific course-dependent process. This process can constitute the course of Apoptosis.
Increasing cell volume is a changing process to change the volume of the cell to increase. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
reduced oxygenation of body tissues resulting in the decreased pressure of this component of body gases; commonly due to hypoxemia This entity is a specific course-dependent process. This process can constitute the course of Cell death.
Fatty acid homeostasis imbalance in peroxisome is a subtype of changing balance: A process that becomes lacking afatty acid homeostastasis balance. The degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
fatty acid homeostasis imbalance in peroxisome (severe) [Eosinophilic granular degeneration]
Refolding gene expression by ATF6 is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) related to the protein refolding function by ATF6. This process is dependent on the refolding and can constitute the course of ER stress.
refolding gene expression by ATF6 [ER stress - refolding]
The active form of ATF6 is produced faster than that of XBP1 in ER-stressed cells because the former is derived from preexisting precursor protein, whereas the latter must be newly translated from mRNA that is transcriptionally induced and then spliced. XBP1 can function in a more sustained fashion than ATF6 because, once produced, the spliced form of XBP1 can keep activating transcription by autoregulating its own transcription as far as IRE1 is activated. In contrast, ATF6 mRNA is not upregulated during ER stress. Low levels of ER stress may be dealt with only by proteolytic activation of ATF6, medium to high levels of ER stress may be handled by activating both ATF6 and IRE1-XBP1 systems, and extremely high levels of ER stress may be overcome by multiple rounds of activation of the XBP1 cycle.
On release from BiP, ATF6α transfers to the Golgi compartment where it is processed by the Golgi enzymes site 1 protease (S1P) and S2P to produce a cytosolic p50 fragment that migrates to the nucleus. The p50 fragment activates the expression of genes encoding proteins that function to increase ER capacity and folding (including, BiP, GRP94, p58IPK (also known as DNAJC3) and XBP1), as well as the ERAD pathway
A role played by the entity which is a first rate-limiting enzyme and regulates the glutathione biosynthetic process.
glutathione biosynthetic limiting enzyme agent role
A role that stimulates a cell to grow or proliferate. Most growth factors have other actions besides the induction of cell growth or proliferation.
Extracellular polypeptide signal molecule that can stimulate a cell grow or proliferate. Examples are EGF and PDGF. Most growth factors also have other actions.
A role played by the entity which involves in poritively regulating a gulutathione expression process.
glutathione expression positive regulator role
A role played by the entity which induces the process of cell death.
An enzyme inhibitor that interferes with the activity of p53.
A role played by the entity which positively regulates the glutathione biosynthetic process.
glutathione biosynthetic promoting agent
A role played by small molecule that is formed in or released into the cytosol in response to an extracellular signal and helps to relay the signal to the interior of the cell. Examples include cAMP, IP3, and Ca++.
A role played by the entity which positively regulates the reduced glutathione biosynthetic process
reduced glutathione biosynthetic promoting agent
The process that results in the movement of cytochrome c from the mitochondrial intermembrane space into the cytosol, which is part of the apoptotic signaling pathway and leads to caspase activation. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
release of cytochrome c from mitochondria [Cell death]
Keap1 inactivation is a subtype of molecular inactivation: A process that changes the activity of the Keap1 to be lower. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
Keap1 inactivation [Glutathione depletion]
BIP-stress sensor complex is a subtype of molecular complex. This entity has sub-parts of molecules, BIP/GRP78 and other molecule which has role of stress sensor.
A role played by the entity which regulates the process of cell death.
Keap1 modification by electrophiles is a subtype of oxidation by electrophiles. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
Keap1 modification by electrophiles [Glutathione depletion]
PLA2G5 (human)(canonical)[Phospholipidosis]
This gene is a member of the secretory phospholipase A2 family. It is located in a tightly-linked cluster of secretory phospholipase A2 genes on chromosome 1. The encoded enzyme catalyzes the hydrolysis of membrane phospholipids to generate lysophospholipids and free fatty acids including arachidonic acid. It preferentially hydrolyzes linoleoyl-containing phosphatidylcholine substrates. Secretion of this enzyme is thought to induce inflammatory responses in neighboring cells. Alternatively spliced transcript variants have been found, but their full-length nature has not been determined. [provided by RefSeq, Jul 2008]
Electrophiles formation is a subtype of biosynthetic process: A process that that generates electrophiles. Electrophile is a reagent that forms a bond to its reaction partner (the nucleophile) by accepting both bonding electrons from that reaction partner. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
A process in which a signal to eIF2a is transduced by PERK. This process is dependent on the refolding and can constitute the course of ER stress.
PERK signaling to eIF2a [ER stress - refolding]
An attribute related to the power or force.
A physical attribute that inheres in a bearer by virtue of the proportion of the bearer's amount of matter.
A 1-D extent attribute which is equal to the distance between two points.
A 3-D extent attribute related to amount of 3-dimensional space it occupies.
A physical attribute relaeted to the amount of force per unit area the bearer exerts.
A physical attribute entity inhering in a bearer by virtue of the bearer's rate of change of momentum.
An attribute to the potential energy per unit charge associated with a static (time-invariant) electric field, also called the electrostatic potential.
An attribute entity inhering in a cell's plasma membrane by virtue of the electrical potential difference across it.
A physical attribute inhering in a bearer by virtue the bearer's disposition to having an affinity for water; it is readily absorbing or dissolving in water.
A physical attribute inhering in a bearer by virtue the bearer's disposition to being water-repellent; tending to repel and not absorb water.
A time attribute inhering in a bearer by virtue of how long the bearer has existed.
An organismal attribute inhering in a bearer by virtue of the bearer's ability to undergo sexual reproduction in order to differentiate the individuals or types involved.
An organismal value of an attribute inhering in a bearer by virtue of the bearer's ability to undergo sexual reproduction in order to differentiate the individuals or types involved.
A biological sex value inhering in an individual or a population that only produces gametes that can be fertilised by male gametes.
A biological sex attribute inhering in an individual or a population whose sex organs contain only male gametes.
An attribute that inheres in a bearer in virtue of its realizing one of its functions.
Negative regulation of inflammatory response is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of inflammatory response. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
negative regulation of inflammatory response [Glutathione depletion]
The cellular catabolic process in which cells digest parts of their own cytoplasm; allows for both recycling of macromolecular constituents under conditions of cellular stress and remodeling the intracellular structure for cell differentiation This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
autophagy dependent Keap1 catabolic process [Glutathione depletion]
Nrf2 target gene products, such as Gst-m1 and Gst-p1, were prominent proteins in autophagy-deficient liver. Surprisingly, Gst-m1 constituted 7.69 ± 1.25% of the cytosolic proteins in Atg7-deficient livers.
The chemical reaction resulting in the breakdown of NRF2, which is mediated by the proteasome.
proteasome-mediated ubiquitin-dependent NRF2 catabolic process
Gene expression by ATF4 is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) by ATF4.
The chemical reaction resulting in the breakdown of NRF2, which is mediated by the proteasome. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
proteasome-mediated NRF2 degradation [Glutathione depletion]
Pancreatic beta cell damage is a subtype of cellular damage: A process that injuries the structure of the pancreatic beta cell as the direct or indirect result of an external force. This entity is a specific course-dependent process. This process can constitute the course of Type I Diabetes mellitus.
pancreatic beta cell damage [Type I Diabetes mellitus]
Dysfunction of dysfunction of insulin secretion is a subtype of dysfunctioning: A process that performs an abnormal and incomplete insulin secretion.
dysfunction of dysfunction of insulin secretion
Dysfunction of insulin secretion is a subtype of dysfunctioning: A process that performs an abnormal and incomplete insulin secretion. This entity is a specific course-dependent process. This process can constitute the course of Type I Diabetes mellitus.
dysfunction of insulin secretion [Type I Diabetes mellitus]
Changing concentration is a subtype of changing quality: A process that changes the concentration of the object.
Decreasing blood glucose level in blood is a subtype of decreasing concentration: A process that changes the blood glucose concentration in the blood to be lower.
A process in which a signal to eIF2a is transduced by PERK. This process is dependent on the apoptosis and can constitute the course of ER stress.
PERK signaling to eIF2a [ER stress apoptosis]
Any process that stops, prevents, or reduces the frequency, rate or extent of the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of ubiquitin, and mediated by the proteasome.
negative regulation of proteasomal ubiquitin-dependent protein catabolic process
Any process that stops, prevents, or reduces the frequency, rate or extent of the breakdown of NRF2 by hydrolysis of its peptide bonds, initiated by the covalent attachment of ubiquitin, and mediated by the proteasome.
negative regulation of proteasomal ubiquitin-dependent NRF2 catabolic process
Overeating is a subtype of increasing quantity: A process that changes the ingestion amount of food to be larger. This entity is a specific course-dependent process. This process can constitute the course of Type II Diabetes mellitus.
Increasing insulin demand is a subtype of increasing functional demand: A process changes the demand for insulin to be higher.
autophagy dependent Keap1 catabolic process
Fatty acid homeostasis imbalance in peroxisome is a subtype of changing balance: A process that becomes lacking afatty acid homeostastasis balance.
fatty acid homeostasis imbalance in peroxisome
Receiving abnormal protein signal by ATF6 is a subtype of receiving signal: A process that recognizes another object and changes into an abnormal protein (e.g., misfolded protein, etc.) signal by ATF6. This process is dependent on the refolding and can constitute the course of ER stress.
receiving abnormal protein signal by ATF6 [ER stress - refolding]
Regulation of beta oxidation related gene expression is a subtype of regulation of gene expression: A process that modulates the frequency, rate or extent of fatty acid beta oxidation related gene expression. This entity is a specific course-dependent process. The degree is severe. This process can constitute the course of Eosinogranular degeneration.
regulation of beta oxidation related gene expression (severe) [Eosinophilic granular degeneration]
A process in which a signal to eIF2a is transduced by PERK. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Hyperfunction of peroxisomal fatty acid beta-oxidation is a subtype of hyperfunction of fatty acid beta-oxidation: A process that performs an excessive peroxisomal fatty acid beta-oxidation. The degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
hyperfunction of peroxisomal fatty acid beta-oxidation (severe) [Eosinophilic granular degeneration]
After 24h treatment with the hepatotoxins, there was evidence for the initiation of a late defence response. BB significantly increased both HO-1 and GCLC protein at this time point, CCl4 increased GCLC protein alone.
Synergistic effects of phorone on the hepatotoxicity of bromobenzene and paracetamol in mice.
Significant GSH depletion was seen with APAP (9.6+/-1.7% of control levels) and BB (52.8+/-6.2% of control levels) 1h after administration, but not with FS and CCl4. Treatment with APAP for 1h caused a significant increase in the levels of haem oxygenase-1 (HO-1; 2.85-fold) and glutamate cysteine ligase (GCLC; 1.62-fold) mRNA. BB and FS did not affect the mRNA levels of either gene after 1h of treatment; however CCl4 significantly increased HO-1 mRNA at this time point. After 24h treatment with the hepatotoxins, there was evidence for the initiation of a late defence response. BB significantly increased both HO-1 and GCLC protein at this time point, CCl4 increased GCLC protein alone.
Signaling molecule activation is a subtype of molecular activation: A process that changes the activity of the molecule with a signaling molecule role to be higher.
Excretion of glutathione conjugates from hepatocyte to bile tube is a subtype of compound excretion: A process that excretes the glutathione conjugates from the hepatocyte to to the bile tube.
excretion of glutathione conjugates from hepatocyte to bile tube
Excretion of glutathione conjugates from hepatocyte to blood is a subtype of compound excretion: A process that excretes the glutathione conjugates from the hepatocyte to to blood.
excretion of glutathione conjugates from hepatocyte to blood
glutathione export from hepatocyte to blood is a subtype of glutathione transport: A process that exports the glutathione from the hepatocyte to to the blood.
glutathione export from hepatocyte to blood
Refolding-unfolding imbalance is a subtype of imbalance: A process that lacks a balance between protein refolding and unfolding. This entity is a specific course-dependent process. This process can constitute the course of ER stress (mild).
refolding-unfolding imbalance [ER stress (mild) ]
Refolding-unfolding imbalance is a subtype of imbalance: A process that lacks a balance between protein refolding and unfolding.
Refolding-unfolding imbalance is a subtype of imbalance: A process that lacks a balance between protein refolding and unfolding. And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of ER stress (moderate).
refolding-unfolding imbalance [ER stress (moderate) ]
PERK-NRF2 signal integration system is a subtype of PERK pathway system. This entity has sub-parts and has a goal of transmitting signals and a gene regulation via PERK and NRF2 as a systemic context.
A physical attribute inhering in a bearer by virtue of the bearer's motion characteristic.
A role of receiving a signal and transmitting it in the cell to initiate a change in cell activity. A signal is a physical entity or change in state that is used to transfer information in order to trigger a response.
Stress sensor activation, is a subtype of molecular activation: A process that changes the activity of the molecule with stress sensor role to be higher.
Transport ATF-6 from the endoplasmic reticulum (ER) to the Golgi is a subtype of ER to Golgi transport: A process of the directed movement of ATF6 from the endoplasmic reticulum (ER) to the Golgi.
Transport ATF-6 from the endoplasmic reticulum (ER) to the Golgi
Transport ATF-6 from the endoplasmic reticulum (ER) to the Golgi is a subtype of ER to Golgi transport: A process of the directed movement of ATF6 from the endoplasmic reticulum (ER) to the Golgi. This process is dependent on the refolding and can constitute the course of ER stress.
The association between ATF6-alpha and BiP causes ATF6-alpha to be retained in the endoplasmic reticulum (ER). Once dissociated from BiP, the 2 Golgi Localization Sequences on ATF6-alpha are exposed and ATF6-alpha transits from the ER to the Golgi Apparatus.
Transport ATF-6 from the endoplasmic reticulum (ER) to the Golgi [ER stress - refolding]
ATF6 processing is a subtype of protein processing: A process that ATF6 maturation process achieved by the cleavage of a peptide bond or bonds within ATF6 protein. This process is dependent on the refolding and can constitute the course of ER stress.
Increasing demand for protein refolding is a subtype of increasing functional demand: A process that changes the functional demand for protein refolding to be higher. This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of ER stress (sustained).
increasing demand for protein refolding [ER stress (sustained)]
Accumulation of abnormal proteins in ER is a subtype of accumulation of abnormal proteins: A process that keeps abnormal protein(s) in the ER (endoplasmic reticulum). And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of ER stress (moderate).
accumulation of abnormal proteins in ER [ER stress (moderate) ]
Increasing demand for protein degradation is a subtype of increasing functional demand: A process that is subjected to increasing load of protein degradation.
increasing demand for protein degradation
Increasing demand for abnormal protein degradation is a subtype of increasing demand of protein degradation: A process is subjected to increasing load of abnormal protein degradation.
increasing demand for abnormal protein degradation
Increasing demand for abnormal protein degradation is a subtype of increasing demand of protein degradation: A process is subjected to increasing load of abnormal protein degradation. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
increasing demand for abnormal protein degradation [ER stress]
Protein refolding insufficiency is a subtype of malfunctioning process: A process that lacks performing the function of protein refolding required.
Protein refolding insufficiency is a subtype of malfunctioning process: A process that lacks performing the function of protein refolding required. This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of ER stress (sustained) .
protein refolding insufficiency (sustained) [ER stress]
Protein degradation insufficiency is a subtype of malfunctioning process: A process that lacks performing the function of protein degradation required.
Protein degradation insufficiency is a subtype of malfunctioning process: A process that lacks performing the function of protein degradation required. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
protein degradation insufficiency [ER stress]
Abnormal protein production- degradation imbalance is a subtype of imbalance: A process that lacks a balance between abnormal protein production and degradation.
abnormal protein production- degradation imbalance
Abnormal protein production- degradation imbalance is a subtype of imbalance: A process that lacks a balance between abnormal protein production and degradation. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
abnormal protein production- degradation imbalance [ER stress]
glutathione export from hepatocyte to bile tube is a subtype of glutathione transport: A process that exports the glutathione from the hepatocyte to to the blood.
glutathione export from hepatocyte to bile tube
A series of reactions within the signal-receiving cell, mediated by the intracellular phosphatidylinositol 3-kinase (PI3K). Many cell surface receptor linked signaling pathways signal through PI3K to regulate numerous cellular functions.
A series of molecular signals mediated by Caspase family.
ATF4 gene regulation pathway is a subtype of gene regulation pathway: Sequence of reactions to regulate genes by ATF4.
ATF4 gene regulation pathway is a subtype of gene regulation pathway: Sequence of reactions to regulate genes by ATF4. This pathway is dependent on the apoptosis and can constitute the course of ER stress.
ATF4 gene regulation pathway [ER stress - apoptosis]
CHOP gene regulation pathway is a subtype of gene regulation pathway: Sequence of reactions to regulate genes by CHOP.
XBP1s gene regulation pathway is a subtype of gene regulation pathway: A series of process in which XBP1s regulates the gene expression.
IRE1-mediated unfolded protein response [ER stress]
glutathione export from hepatocyte is a subtype of glutathione transport: A process that exports the glutathione from the hepatocyte.
GSH itself is often cotranported with other xenobiotics or xenobiotics metabolites, namely, by MRP2 into bile, and by MRP1,4,5 into blood. Casarett & Doull's Toxicology: The Basic Science of Poisons, Eighth Edition
The Mrp proteins mediate not only GSH efflux, but they also export oxidized glutathione derivatives (e.g., glutathione disulfide (GSSG), S-nitrosoglutathione (GS-NO), and glutathione-metal complexes), as well as other glutathione S-conjugates.
PI3K-AKT signaling is a subtype of integrated signaling pathway: Sequence of linked reactions, which has PI3 signaling and activation of the AKT gene.
NRF2 signaling (integrated pathway) is a subtype of integrated signaling pathway: Sequence of linked reactions, which has NRF2 signaling and gene regulation pathway.
nuclear factor erythroid 2 like 2 signaling pathway
glutathione export from hepatocyte is a subtype of glutathione transport: A process that exports the glutathione from the hepatocyte. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
glutathione export from hepatocyte [Glutathione depletion]
Dissociation of NF-kappaB -I-kappaB is a subtype of detaching: A process that disaggregates a NF-kappaB-I-kappaB to NF-kappaB dimers and I-kappaB. In a resting state, NF-kappaB dimers are bound to I-kappaB proteins, sequestering NF-kappaB in the cytoplasm. Phosphorylation of I-kappaB targets I-kappaB for ubiquitination and proteasomal degradation, thus releasing the NF-kappaB dimers, which can translocate to the nucleus to bind DNA and regulate transcription.
The release of NF-kappaB from specific molecules in the cytoplasm to which it was bound, thereby allowing its translocation into the nucleus.
NF-kappaB transport into nucleus is a subtype of nuclear transport: A process that of the directed movement of NF-kappaB from the cytoplasm to the nucleus.
The process of introducing a phosphate group into an inhibitor of kappa B (I-kappaB) protein. Phosphorylation of I-kappaB targets I-kappaB for ubiquitination and proteasomal degradation, thus releasing bound NF-kappaB dimers, which can translocate to the nucleus to bind DNA and regulate transcription. PMID:21772278
ATP Binding Cassette Subfamily C Member 2
ATP-Binding Cassette, Sub-Family C (CFTR/MRP), Member 2
Canalicular Multispecific Organic Anion Transporter 1
Multidrug Resistance-Associated Protein 2
IGFBP1 gene expression by ATF4 is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature IGFBP1 product or products (proteins or RNA) by ATF4. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
IGFBP1 gene expression by ATF4 [ER stress]
Abnormal protein production is a subtype of protein production: A process that makes existent of an abnormal protein due to biosynthesis or secretion resulting in an increase in its levels. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
ATP Binding Cassette Subfamily C Member 1
ATP-Binding Cassette, Sub-Family C (CFTR/MRP), Member 1
Multidrug Resistance-Associated Protein 1
Hyperfunction of protein unfolding is a subtype of hyperfunctioning: A process that performs an excesssive protein unfolding. This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of ER stress (sustained) .
hyperfunction of protein unfolding (sustained) [ER stress]
Accumulation of compound in ER is a subtype of accumulation of xenobiotics: A process that keeps compound in the ER (endoplasmic reticulum). This entity is a specific course-dependent process. This process can constitute the course of ER stress (severe) .
accumulation of compound in ER [ER stress (severe) ]
Hyperfunction of repeated protein unfolding is a subtype of hyperfunctioning: A process that performs an excesssive protein unfolding. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
hyperfunction of repeated protein unfolding [ER stress]
Protein aggregation is a subtype of molecular assembly: The aggregation, arrangement and bonding together of molecules. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Protein aggregating [ER stress] is an assembling process to make proteins an aggregate in the course of ER stress.
A process that changes the activity of the eIF2a by PERK. This process is dependent on the translation attenuation and can constitute the course of ER stress.
changing activity of eIF2a by PERK [ER stress - translation attenuation]
Phosphorylation of eIF2-alpha by PERK is a subtype of eIF2a phosphorylation: A process that The process of introducing a phosphate group into eIF2a by PERK. This process is dependent on the translation attenuation and can constitute the course of ER stress.
Phosphorylation of eIF2-alpha by PERK [ER stress - translation attenuation]
Phosphorylation of eIF2-alpha by PERK is a subtype of eIF2a phosphorylation: A process that The process of introducing a phosphate group into eIF2a by PERK. This process is dependent on the refolding and can constitute the course of ER stress.
Phosphorylation of eIF2-alpha by PERK [ER stress - refolding]
Phosphorylation of eIF2-alpha by PERK is a subtype of eIF2a phosphorylation: A process that The process of introducing a phosphate group into eIF2a by PERK. This process is dependent on the apoptosis and can constitute the course of ER stress.
Phosphorylation of eIF2-alpha by PERK [ER stress - apoptosis]
Phosphorylation of eIF2-alpha by PERK is a subtype of eIF2a phosphorylation: A process that The process of introducing a phosphate group into eIF2a by PERK. This process is dependent on the inflammation and can constitute the course of ER stress.
Phosphorylation of eIF2-alpha by PERK [ER stress - inflammation]
Chaperone gene regulation pathway by ATF6 is a subtype of ATF6 gene regulation pathway: Sequence of reactions to regulate genes which have a chaperone role by ATF6. This process can constitute the course of ER stress.
chaperone gene regulation pathway by ATF6 [ER stress]
PERK-eIF2a-ATF4 mediated pathway is a subtype of PERK-eIF2a signaling: Sequence of linked reactions, which has PERK-eIF2a signaling and gene regulation by ATF4.
PERK activation is a subtype of Molecular activation: A process that changes the activity of PERK to be higher. This process is dependent on the translation attenuation and can constitute the course of ER stress.
PERK activation [ER stress - translation attenuation]
PERK activation is a subtype of Molecular activation: A process that changes the activity of PERK to be higher. This process persists for a certain period or over a long period. This process is dependent on the apoptosis (sutained) and can constitute the course of ER stress.
PERK activation [ER stress - apoptosis (sutained ) ]
PERK activation is a subtype of Molecular activation: A process that changes the activity of PERK to be higher. This process is dependent on the refolding and can constitute the course of ER stress.
A process that changes the activity of the eIF2a by PERK. This process is dependent on the apoptosis and can constitute the course of ER stress.
changing activity of eIF2a by PERK [ER stress - apoptosis]
A process that changes the activity of the eIF2a by PERK. This process is dependent on the refolding and can constitute the course of ER stress.
changing activity of eIF2a by PERK [ER stress - refolding]
PERK-eIF2a-ATF4-CHOP pathway is a subtype of PERK-eIF2a-ATF4 signaling: Sequence of linked reactions, which has PERK-eIF2a-ATF4 signaling and gene regulation by CHOP. This pathway is dependent on the apoptosis and can constitute the course of ER stress.
PERK-ATF4-CHOP signaling [ER stress - apoptosis]
ATF6 gene regulation pathway is a subtype of gene regulation pathway: Sequence of reactions to regulate genes by ATF6.
The process in which a gene's sequence is converted into a mature gene product or products (proteins or RNA) by ATF6. is a subtype of Gene expression by transcriptional regulator: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) by ATF6.
The process in which a gene's sequence is converted into a mature gene product or products (proteins or RNA) by ATF6.
CAD accumulation in lysosome is a subtype of compound accumulation in lysosome: A process that keeps CAD (Cationic Amphiphilic Drugs) in the lysosome. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (latent).
CAD accumulation in lysosome [Phospholipidosis (latent)]
NRF2 gene expression regulation system is a subtype of pathway system. This entity has sub-parts and has a goal of regulating gene expressions by NRF2 as a systemic context.
The totality of all processes through which endoplasmic reticulum (ER) stress is realized.
The ER stress is a cellular response that occurs after sustained pertubation of ER protein synthesis, folding, and export machinery. Tis is likely to be induced by oxidative or covalent modification of ER proteins, which leads to misfolding of proteins.
endoplasmic reticulum stress [toxic course]
Drug-Induced Liver Disease 3rd Edition Editors: Neil Kaplowitz Laurie DeLeve Academic Press 2013
Aggregated protein production- degradation imbalance is a subtype of imbalance: A process that lacks a balance between aggregated protein production and degradation. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
aggregated protein production- degradation imbalance [ER stress]
Aggregated protein production- degradation imbalance is a subtype of imbalance: A process that lacks a balance between aggregated protein production and degradation.
aggregated protein production- degradation imbalance
Increasing number of abnormal cells in liver is a subtype of cell proliferation: A process that becomes larger in the number of autodigestion of abnormal cells in the liver.
increasing number of abnormal cells in liver
Increasing number of abnormal cells in liver is a subtype of cell proliferation: A process that becomes larger in the number of autodigestion of abnormal cells in the liver. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
increasing number of abnormal cells in liver [ER stress]
Hyperfunction of cell survival is a subtype of hyperfunctioning: A process that performs an excesssive cell survival. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
hyperfunction of cell survival[ER stress]
A pathologic process that involves the transformation of normal cells to a neoplastic state. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Tumor cell proliferation is a subtype of cell proliferation: A process of the multiplication or reproduction of tumor cells, resulting in the rapid expansion of a tumor cell population. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Increasing hepatocellular volume is a changing process to change the volume of the hepatocyte to increase. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
increasing hepatocellular volume [ER stress]
Negative regulation of increasing insulin resistance is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of insulin resistance.
negative regulation of increasing insulin resistance
Increasing volume of liver is a subtype of increasing volume: A process that changes the volume of the liver to be higher. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Protein quality control for misfolded or incompletely synthesized proteins is a subtype of keeping quality: A process that maintains the protein quality in an early stage of toxic course. This entity is a specific course-dependent process. This process can constitute the course of ER stress (early stage).
protein quality control for unfolded proteins [ER stress (early stage)]
BIP- chaperone [ER stress - refolding [early stage]
HEL-S-89n- chaperone [ER stress - refolding [early stage]
HSPA5- chaperone [ER stress - refolding [early stage]
Heat Shock Protein Family A (Hsp70) Member 5- chaperone [ER stress - refolding [early stage]
MIF2- chaperone [ER stress - refolding [early stage]
GRP78 - chaperone (canonical)[ER stress - refolding [early stage]
Optional contribution processis a subtype of meta-functioning and it represents optional contribution to functioning. The “optional” means that the effect of fa is not mandatory to ft, that is, ft can be performed without the effect of fa.
Enhancing is a type of functioning process of meta-function. Both enhancing and improveing represents optional contribution to other function. The “optional” means that the effect of fa is not mandatory to ft, that is, the target function can be performed without improving or enhancing. The discrimination between improving and enhancing is made by whether augmentation of the output can be made without increase of the amount of the input energy or not. For example, the “to make low pressure” of the condenser contributes to the efficiency of the “to generate torque” function without increment of input energy, so its functioning is “Improving”. On the other hand, the “to super-heat” function of the boiler optionally increases the amount of the input energy to make a contribution. Its meta-function is “Enhancing” .
A chromosome that encodes the nuclear genome and is found in the nucleus of a eukaryotic cell during the cell cycle phases when the nucleus is intact.
Protein quality control for misfolded or incompletely synthesized proteins is a subtype of keeping quality: A process that maintains the protein quality. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
protein quality control for unfolded proteins [ER stress]
Regulation of lipolytic gene expression is a subtype of regulation of gene expression: A process that modulates the frequency, rate or extent of lipid degradation related gene expression.
Refolding promoting gene expression by ATF6 is a subtype of gene expression: The process in which a gene sequence is converted into a mature refolding inducing gene product or products (proteins or RNA) by ATF6 . This entity is a specific course-dependent process. This process can constitute the course of ER stress.
refolding promoting gene expression by ATF6 [ER stress]
Negative regulation of increasing insulin resistance is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of insulin resistance. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
negative regulation of increasing insulin resistance [ER stress]
ATF6 signaling (integrated pathway) is a subtype of integrated signaling pathway: Sequence of linked reactions, which has ATF6 signaling and gene regulation pathway.
ATF6 mediated chaperon gene regulation pathway is a subtype of ATF6 signaling (integrated pathway): Sequence of linked reactions, which has ATF6 signaling and gene regulation pathway. This process is dependent on the refolding and can constitute the course of ER stress.
ATF6 mediated chaperon gene producion pathway [ER stress -refolding]
ATF6 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the ATF6 (activating transcription factor 6). ATF6 generally plays a endoplasmic reticulum membrane stress sensor role. This process is dependent on the refolding and can constitute the course of ER stress.
ATF6 signaling (primitive) [ER stress - refolding]
Excretion of glutathione conjugates from hepatocyte is a subtype of compound excretion: A process that excretes the glutathione conjugates from the hepatocyte.
excretion of glutathione conjugates from hepatocyte
Blood coagulation factor synthesis is a subtype of biosynthetic process: The chemical reactions resulting in the formation of substances with blood coagulation factor role.
CYP4A11 - tumor progression marker (human)[Phospholipidosis]
CYP4A11 expression level was higher in non-neoplastic hepatocytes than those in HCC cells (P < 0.001), and CYP4A11 expression positively correlated with favorable prognostic factors, including tumor size, histological grade, and pathological tumor stage (P = 0.007, P = 0.005, and P = 0.007)
Receiving signal in ATF6 signal transduction pathway is a subtype of receiving signal: A process that recognizes another object and changes into a signal in a ATF6 signal transduction pathway. This entity is a specific course-dependent process. This process can constitute the course of ATF6 pathway.
This gene encodes a eukaryotic translation initiation factor that catalyzes the formation of puromycin-sensitive 80 S preinitiation complexes and the poly(U)-directed synthesis of polyphenylalanine at low concentrations of Mg2+. This gene should not be confused with eIF2-alpha (EIF2S1, Gene ID: 1965), the alpha subunit of the eIF2 translation initiation complex. Although both of these proteins function in binding initiator tRNA to the 40 S ribosomal subunit, the encoded protein does so in a codon-dependent manner, whereas eIF2 complex requires GTP. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]
P-EIF2A - translation initiation inhibitor (canonical)[ER stress - translation attenuation]
phosphorylated eIF2A -ATF4 promoting factor [ER stress - proteinrefolding]
P-EIF2A -ATF4 promoting factor (canonical)[ER stress - proteinrefolding]
A role played by the entity which modulates the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of proteins by the translation of mRNA or circRNA.
ATF4 - transcriptional regulator (canonical)[ER stress - apotosis]
ATF4 - transcriptional regulator (canonical)[ER stress - inflammation]
ATF4 - transcriptional regulator (canonical)[ER stress - insulin resistance]
PERK-eIF2a-ATF4 mediated pathway is a subtype of PERK-eIF2a signaling: Sequence of linked reactions, which has PERK-eIF2a signaling and TRIB3 gene regulation by ATF4. This pathway is dependent on the insulin resistance and can constitute the course of ER stress.
PERK-ATF4-TRIB3 signaling [ER stress - insulin resistance]
Trib3 gene expression by ATF4 is a subtype of gene expression by transcriptional factor: The process in which a gene sequence of Trib3 is converted into a mature gene product or products (proteins or RNA) related to the refolding by ATF4. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Trib3 gene expression by ATF4 [ER stress]
IRE1 signaling (integrated pathway) is a subtype of integrated signaling pathway: Sequence of linked reactions, which has IRE1 signaling and gene regulation pathway.
Excretion of glutathione conjugates from hepatocyte is a subtype of compound excretion: A process that excretes the glutathione conjugates from the hepatocyte. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
excretion of glutathione conjugates from hepatocyte [Glutathione depletion.]
Changing protein fold is a subtype of changing protein structure: A process that changes the folding stucture of the protein.
Changing structure is a subtype of changing an operand: A process that change sthe stucture of the operand.
Converting to information is a subtype of converting type: A process that changes a type of object to information.
Changing composition is a subtype of changing between operands: A process that changes the relationship of the overall components.
Combining is a subtype of assembling: A process that merges different parts into one. Each element can be recognized after combination.
Dissolving is a subtype of assembling: A process that creates a solvent-solute relationship between components.
IRE1 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the IRE1 (Inositol-requiring transmembrane kinase/endonuclease). IRE1 generally plays a endoplasmic reticulum membrane stress sensor role. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
CAD insertion into phospholipase binding site to lysosomal inner membrane is a subtype of binding: A process that CAD inserts and replaces the phospholipase binding site in the lysosomal inner membrane. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (latent).
CAD insertion into phospholipase binding site to lysosomal inner membrane [Phospholipidosis (latent)]
Mixing is a subtype of assembling: A process that combines two or more substances to a single element, and they cannot be distinguished.
Composing is a subtype of assembling: A process that makes the different constituents into a connected whole.
Gathering is a subtype of assembling: A process that groups components of the same type.
Splitting is a subtype of separating: A process that divides the whole object into the same kinds of parts. A + A+ A
Taking is a subtype of separating: A process that separates and chooses an object .
Extracting is a subtype of taking: A process that obtains a necessary component from the whole object
異種成分の１つに注目して取り出すこと
FNIP2 (predicted)(human)[Phospholipidosis]
Decreasing distance is a subtype of changing distance: A process that brings object A close to object B.
Making contact between A and B is a subtype of decreasing distance: A process that brings object A close to object B to set the distance to 0.
Glutathione conjugation (supply) - function demand imbalance (severe) is a subtype of imbalance: A process that becomes lacking a homeostastasis balance between glutathione conjugation supply and demand. The degree is severe This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
Glutathione conjugation (supply) - function demand imbalance (severe) [Glutathione depletion]
Keeping distance is a subtype of changing distance: A process that maintains the relative positional relationship between objects.
Keeping adhesivity is a subtype of keeping distance: A process that maintains the relative positional relationship between objects with no distance.
Keeping distance (d>0) is a subtype of keeping distance: A process that maintains the relative positional relationship between objects with a certain distance (>0) .
Changing the relationship between inside and outside is a subtype of changing position: A process that that changes the relative position between an inside object and an outside object.
changing the relationship between inside and outside
Moving A to the inside of B is a subtype of changing the relationship between inside and outside: A process that that places an object from the outside to the inside of the boundary.
Moving A to the outside of B is a subtype of changing the relationship between inside and outside: A process that that places an object from the inside to the outside of the boundary.
Discharging unnecessary object is a subtype of giving: A process that sends out an unnecessary object to an other medium.
Changing material is a subtype of changing relationship between operands: A process that replaces the old material into new material.
IRE1 activation is a subtype of molecular activation: A process that changes the activity of the IRE1 to be higher. This entity is a specific course-dependent process. This process can constitute the course of IRE1 pathway.
XBP1 activation by IRE1 is a subtype of activation of transcription factor: A process that changes the activity of XBP1 (X-Box Binding Protein 1) to be higher by IRE1. This entity is a specific course-dependent process. This process can constitute the course of IRE1 pathway.
The XBP1 gene is transcribed to yield mRNA, which is spliced and translated to transcription factor Xbp(s).
IRE1 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the IRE1 (Inositol-requiring transmembrane kinase/endonuclease). IRE1 generally plays a endoplasmic reticulum membrane stress sensor role. This entity is a specific course-dependent process. This process can constitute the course of IRE1 pathway.
IRE1 signaling (primitive) [IRE1 pathway]
A process in which a signal to TRAF2 is transduced by the IRE1. This process is dependent on the inflammation and can constitute the course of ER stress.
IRE1 signaling to TRAF2 [ER stress - inflammation]
IRE1 dimerization is a subtype of protein dimerization: The formation of a IRE1 dimer, a macromolecular structure consists of two noncovalently associated identical or nonidentical subunits.
IRE1 dimerization is a subtype of protein dimerization: The formation of a IRE1 dimer, a macromolecular structure consists of two noncovalently associated identical or nonidentical subunits. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
IRE1 autophosphorylation is a subtype of protein autophosphorylation: The phosphorylation by IRE1 of one or more of its own amino acid residues (cis-autophosphorylation), or residues on IRE1 (trans-autophosphorylation).
IRE1 autophosphorylation is a subtype of protein autophosphorylation: The phosphorylation by IRE1 of one or more of its own amino acid residues (cis-autophosphorylation), or residues on IRE1 (trans-autophosphorylation). This entity is a specific course-dependent process. This process can constitute the course of ER stress.
IRE1-Traf2-ASK-JNK-AP1 pathway is a subtype of IRE1 signaling (integrated pathway): Sequence of linked reactions, which has IRE1-Traf2-ASK-JNK signaling and gene regulation by AP1. This pathway is dependent on the inflammation and can constitute the course of ER stress.
IRE1-TRAF2-ASK1 complex A protein complex of the endoplasmic reticulum membrane that consists of IRE1 (Inositol-requiring enzyme-1), TRAF2 (TNF receptor-associated factor 2) and ASK1 (Apoptosis signal-regulating kinase 1, a MAP3K). http://purl.obolibrary.org/obo/GO_1990604
IRE1-Traf2-ASK-JNK-AP1 pathway [ER stress - inflammation]
The IRE1α–TRAF2 complex can, in addition to the activation of NF-κB, recruit ASK1( also known as MAP3K5) and can activate JNK, leading to the increased expression of pro-inflammatory genes through enhanced AP1 activity
Hyperfunction of moving drug to the inside of liver is a subtype of hyperfunction of moving A to the inside of B: A process that performs an excesssive moving drug to the inside of liver. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
hyperfunction of moving drug to the inside of liver [Ground glass appearance]
IRE1 - signal sensor (canonical)[IRE1 signalling system]
IRE1 - signaling factor (canonical)[IRE1 signalling system]
Receiving signal in IRE1 signal transduction pathway is a subtype of receiving signal: A process that recognizes another object and changes into a signal in a IRE1 signal transduction pathway. This entity is a specific course-dependent process. This process can constitute the course of IRE1 pathway.
receiving signal in IRE1 signal transduction pathway [ILE1 pathway]
XBP1 - transcriptional regulator (canonical)[ER stress -ERAD]
Gene expression by XBP1 is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) by XBP1.
Gene expression by XBP1 is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) by XBP1. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
ERAD gene expression by XBP1 is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA)related to the ER associated degradation (ERAD) by XBP1. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
ERAD gene expression by XBP1 [ER stress]
IRE1-XBP1 mediated pathway is a subtype of IRE1 signaling (integrated pathway): Sequence of linked reactions, which has IRE1 signaling and gene regulation by XBP1. This process is dependent on refolding and can constitute the course of ER stress.
IRE1-XBP1 mediated pathway [ER stress - refolding]
IRE1-XBP1 mediated pathway is a subtype of IRE1 signaling (integrated pathway): Sequence of linked reactions, which has IRE1 signaling and gene regulation by XBP1. This process is dependent on ERAD and can constitute the course of ER stress.
IRE1-XBP1 mediated pathway [ER stress - ERAD]
Hyou gene expression by XBP1 is a subtype of gene expression by transcriptional factor: The process in which a Hyou gene sequence is converted into a mature gene product or products (proteins or RNA) by XBP1. This process is dependent on the refolding and can constitute the course of ER stress.
Hyou gene expression by XBP1 [ER stress - refolding]
DNAJB9 gene expression by XBP1 is a subtype of gene expression by transcriptional factor: The process in which a DNAJB9 gene sequence is converted into a mature gene product or products (proteins or RNA) by XBP1. This process is dependent on the refolding and can constitute the course of ER stress.
DNAJB9 gene expression by XBP1 [ER stress - refolding]
Hyperfunctio of glutathione conjugates excretion from hepatocyte is a subtype of compound excretion: A process that excretes the glutathione conjugates from the hepatocyte. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
hyperfunction of glutathione conjugates excretion from hepatocyte [Glutathione depletion]
A release process of the cholesterol from one side of a membrane of hepatocyte to the other side of canaliculus. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
cholesterol efflux (from heptocyte menbrane to canaliculus) [cholestasis]
Enabling translation is a subtype of enabling: A process that sets conditions for translation to work correctly.
Antioxidant gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature antioxidant gene product or products (proteins or RNA). This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Heat Shock Protein Family A (Hsp70) Member 5
GRP78 - stress sensor inhibitor (canonical)[ER stress - proteinrefolding [short-term]]
A role played by the entity that inhibits or desensitizes the stress sensor. By dissociating this inhibitor from the sensor, it can be received the stress and converted into a molecular signal.
negative regulator role of stress sensor
BIP- stress sensor inhibitor [ER stress - proteinrefolding [persist] -IRE1 pathway]
HSPA5- stress sensor inhibitor [ER stress - proteinrefolding [persist] -IRE1 pathway]
Heat Shock Protein Family A (Hsp70) Member 5 - stress sensor inhibitor [ER stress - proteinrefolding [persist] -IRE1 pathway]
GRP78 - stress sensor inhibitor (canonical)[ER stress - proteinrefolding [persist] -IRE1 pathway]
BIP- stress sensor inhibitor[ER stress - proteinrefolding [persist] -ATF6 pathway]
HEL-S-89n- stress sensor inhibitor [ER stress - proteinrefolding [persist] -ATF6 pathway]
HSPA5- stress sensor inhibitor [ER stress - proteinrefolding [persist] -ATF6 pathway]
Heat Shock Protein Family A (Hsp70) Member 5- stress sensor inhibitor [ER stress - proteinrefolding [persist] -ATF6 pathway]
MIF2- stress sensor inhibitor[ER stress - proteinrefolding [persist] -ATF6 pathway]
GRP78 - stress sensor inhibitor (canonical)[ER stress - proteinrefolding [persist] -ATF6 pathway]
PERK-eIF2a-ATF4 mediated pathway is a subtype of PERK-eIF2a signaling: Sequence of linked reactions, which has PERK-eIF2a signaling and gene regulation by ATF4. This pathway is dependent on the inflammation and can constitute the course of ER stress.
PERK-eIF2a-ATF4 pathway [ER stress - inflammation]
PERK - signal sensor (canonical)[ER stress - translation attenuation]
A release process of the phosphatidylcholine from one side of a membrane of hepatocyte to the other side of canaliculus. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
Bile salts, by acting as detergents, release phosphatidylcholine from the outer can canalicular leaflet into the canaliculus
phosphatidylcholine efflux (from heptocyte menbrane to canaliculus) [cholestasis]
A release process of the phospholipids from one side of a membrane of hepatocyte to the other side of canaliculus. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
Bile is rich in phospholipids and organic anions such as bilirubin conjugates. Phospholipids are the main component of biliary lipids and need MFR3 (multidrug resistance protein 3, ABCB4) to enter the canalicular bile . This ABC transporter translocates the main biliary lipid phosphatidylcholine from the inner to the outer leaflet of the canalicular membrane. Bile salts, by acting as detergents, release phosphatidylcholine from the outer can canalicular leaflet into the canaliculus. Cholesterol release from the canalicular membrane it; in part mediated by the heterodimeric ABC transporter ABCG5/ABCG8 (ABCG5/ABCG8)
phospholipid efflux (from heptocyte menbrane to canaliculus) [cholestasis]
A role played by the entity which enables the transmembrane transfer of an ion by a channel that opens when a specific intracellular ligand has been bound by the channel complex or one of its constituent parts.
Autophagy regulator is a role played by any compound that regulates the process of autophagy (the self-digestion of one or more components of a cell through the action of enzymes originating within the same cell).
A release process of the bile from one side of a membrane of hepatocyte to the other side of canaliculus druing the cholestasis. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
Export into the canaliculus is mediated by the BSEP (bile salt export pump, ABCB11) .
Bile circulation (whole body): From the blood vessel side (sinusoidal side) -> hepatocyte ttransport -> bile secretion/excretion from the bile duct side membrane to the capillary bile duct, then to the bile duct, duodenum, intestinal hepatic circulation. Hepatocytes have polarity and have transporters in the membranes on the side of the sinusoidal side and the bile duct. Sinusoid side: OATP family (OATP 1 B 1, OATP 1 B 3): organic anion NTCP: Na dependent uptake MRP 3, 4: Excretion of organic anion from inside the liver into sinusoids Bile duct membrane side: BSEP (ABCG 11): (amino acid conjugation) excretion of bile acid into the bile canaliculi MRP 2: Excretion of organic anions such as sulfate conjugated bile acid, glucuronic acid conjugated bile acid, conjugated bilirubin MDR1: cation excretion MDR 3: phospholipid excretion ABCG 5 / ABCG 8: cholesterol excretion
bile secretion (from heptocyte menbrane to canaliculus) [cholestasis]
A release process of organic anions from one side of a membrane of hepatocyte to the other side of canaliculus. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
Biliary organic anions other than bile salts are mainly conjugates of bilirubin and GSH. Drug metabolites excreted into bile are also organic anions, which are transported by the two ABC transporters, MRP2 (canalicular multi specific organic anion transport 1/multi drug resistance-associated protein 2, ABCC2) and ABCG2 (ABCG2).
Conjugates of glutathione, glucuronide, and sulfate are exported by multidrug resistance-associated protein2 (MRP2).
oranic anion export (from heptocyte menbrane to canaliculus) [cholestasis]
NF-kappaB transport into nucleus is a subtype of nuclear transport: A process that of the directed movement of NF-kappaB from the cytoplasm to the nucleus. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Drug export from the hepatocyte to to bile tube is a subtype of compound excretion: A process that excretes the drug from the hepatocyte to the bile tube. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
Export into the canaliculus is mediated by MDR1 . MDR1 is also expressed at many oegan boundaries.
drug export from the hepatocyte to to bile tube [Cholestasis]
Expcretion of drug metabolite from hepatocyte to bile tube is a subtype of excretion of compound: A process that excretes the drug metabolite from the hepatocyte to to the bile tube. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
Export into the canaliculus is mediated by MDR1 . MDR1 is also expressed at many organ boundaries.
expcretion of drug metabolite from hepatocyte to bile tube [cholestasis]
The directed movement of drugs into hepatocyte vascular side (sinusoidal side) membrane. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
importing substance into hepatocyte vascular side (sinusoidal side) membrane [cholestasis] [Cholestasis]
Bile tube occlusion is a subtype of occlusion: Obstruction or a closure of bile tube. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
Bile salts activate a bile sil sensor, FXR (bile acid receptor; NR1H4) in hepatocytes.
FARNESOID X-ACTIVATED RECEPTOR [cholestasis]
Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis. Clinical features of severe, NR1H4-related cholestasis include neonatal onset with rapid progression to end-stage liver disease, vitamin K-independent coagulopathy, low-to-normal serum gamma-glutamyl transferase activity, elevated serum alpha-fetoprotein and undetectable liver bile salt export pump (ABCB11) expression.
Farnesoid X receptor activation is a subtype of activating nuclear receptor: A process that changes the activity of the activating FxR (farnesoid X receptor) with a nuclear receptor role to be higher. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
Bile salts activate a bile salt sensor, FXR (bile acid receptor; NR1H4) in hepatocytes.
farnesoid X receptor activation [Cholestasis]
Positive regulation of bile export is a subtype of positive regulation process: A process that that activates or increases the frequency, rate or extent of bile acid secretion. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
FXR regulates of metabolic processes. Activation of FXR by increased bile salt concentrations in hepatocytes downregulates the uptake systems for bile salts and maintains or upregulates bill salt efflux systems
positive regulation of bile export [Cholestasis]
Negative regularuion of bile acid and bile salt transport is a subtype of negative regulation of transport: Any process that stops, prevents, or reduces the frequency, rate or extent of a bile acid and bile salts transport . This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
トランスポーター遺伝子の発現を変えることで阻害
negative regularuion of bile acid and bile salt transport [Cholestasis]
oeganic cation transporter [Cholestasis]
Decreasing cross-sectional area is a subtype of decreasing area: A process that changes the cross-sectional area of the object to be smaller.
The regulated release of bile acid, composed of any of a group of steroid carboxylic acids occurring in bile, by a cell or a tissue. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
Impairment of the bile flow caused by obstruction within the liver.
Impairment of the bile flow caused by an obstruction in the portion of the bile duct system located outside of the liver.
Binding to bile canaliculus membrane transporter by drug is a subtype of protein binding: Interacting process with the membrane transporter of bile canaliculus by the drug. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
binding to bile canaliculus membrane transporter by drug [Cholestasis]
Bile transport (import-export) imbalance is a subtype of imbalance: A process that lacks a balance between bile import and export.
bile transport (import-export) imbalance
Bile transport (import-export) imbalance is a subtype of imbalance: A process that lacks a balance between bile import and export. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
bile transport (import-export) imbalance [Cholestasis]
Biliary tract stenosis is a subtype of decreasing cross-sectional area: A process that changes the cross-sectional area of the biliary tract to be smaller.
Changing topology is a subtype of changing structure: A process that changes the setting of the subsets of a topological space.
Decreasing bile flow in bile canaliculus is a subtype of decreasing bile flow: A process that changes the amount of bile flow in bile canaliculus to be lower. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
decreasing bile flow in bile canaliculus [Cholestasis]
Decreasing bile acid production level is a subtype of decreasing quantity: A process that changes the production amount of bile acid to be lower. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
decreasing bile acid production level [Cholestasis]
Regulation of bile acid and bile salt transport is a subtype of regulation of transport (biology): Any process that modulates the frequency, rate or extent of the directed movement of bile acid and bile salts . This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
regulation of bile acid and bile salt transport [Cholestasis]
Bile thrombus formation in bile canaliculus is a subtype of bile thrombus formation: A process that constructs bile thrombus in bile canaliculus. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
bile thrombus formation in bile canaliculus [Cholestasis]
Protein aggregation is a subtype of molecular assembly: The aggregation, arrangement and bonding together of molecules.
Increasing vomume of bile canaliculus is a subtype of increasing volume: A process that changes the volume of the bile canaliculus to be higher. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
increasing vomume of bile canaliculus [Cholestasis]
Increasing canalicular membrane permeability is a subtype of increasing membrane permeabilization: A process that changes the permeability of the canalicular membrane to be higher. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
increasing canalicular membrane permeability [Cholestasis]
Bile reflux is a subtype of back-flow: A process that changes the bile flow to the opposite direction. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
Regulation of cell survival is a subtype of controlling: A process that modulates the frequency, rate or extent of cell survival.
Contraction of bile canaliculus is a subtype of contraction: A process that generates the directed movement in which the bile canaliculus decreases in volume. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
contraction of bile canaliculus [Cholestasis]
Negative regulation of contractile movement of bile canaliculus is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of contractile movement of bile canaliculus. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
negative regulation of contractile movement of bile canaliculus [Cholestasis]
phospholipidosis dependent molecule (HepG2_24h_sawada)
A type of cell death that is morphologically characterized by an increasingly translucent cytoplasm, swelling of organelles, minor ultrastructural modifications of the nucleus (specifically, dilatation of the nuclear membrane and condensation of chromatin into small, irregular, circumscribed patches) and increased cell volume (oncosis), culminating in the disruption of the plasma membrane and subsequent loss of intracellular contents. Necrotic cells do not fragment into discrete corpses as their apoptotic counterparts do. Moreover, their nuclei remain intact and can aggregate and accumulate in necrotic tissues. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
Inflammatory response is a subtype of changing material: The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
The totality of all processes through which a given type I diabetes instance is realized.
Decreasing flow is a subtype of decreasing quantity: A process that changes the amount of flow to be lower.
Decreasing flow is a deacreasing process to decrease the magnitude of the flow.
Decreasing bile flow is a subtype of decreasing flow: A process that changes the amount of bile flow to be lower.
Decreasing bile flow is a subtype of decreasing flow: A process that changes the amount of bile flow to be lower. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
Enterohepatic circulation is a subtype of changing between operands: Bile salts secreted by the liver pass into the intestine, are absorbed in large part by the ileum, and return to the liver by way of the portal vein. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
Increasing bile concentration in blood is a subtype of increasing concentration: A process that changes the concentration of the bile in the blood to be higher. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
increasing bile concentration in blood [Cholestasis]
GRP78 - chaperone (canonical)[ER stress - proteinrefolding (sustained)]
ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of Golgi localization signals. Dev. Cell 3: 99-111, 2002. ATF6 is an endoplasmic reticulum (ER) stress-regulated transmembrane transcription factor that activates the transcription of ER molecular chaperones. Upon ER stress, ATF6 translocates from the ER to the Golgi where it is processed to its active form. ER chaperone BiP/GRP78 binds ATF6 and dissociates in response to ER stress. BiP retains ATF6 in the ER by inhibiting its GLSs and that dissociation of BiP during ER stress allows ATF6 to be transported to the Golgi.
ERdj5 is required as a disulfide reductase for degradation of misfolded proteins in the ER. Science 321: 569-572, 2008. Misfolded or unassembled proteins are discarded by ER-associated degradation (ERAD), which involves their retrotranslocation into the cytosol. ERAD substrates frequently contain disulfide bonds that must be cleaved before their retrotranslocation. ER-resident protein ERdj5 had a reductase activity, cleaved the disulfide bonds of misfolded proteins, and accelerated ERAD through its physical and functional associations with EDEM (ER degradation-enhancing alpha-mannosidase-like protein) and an ER-resident chaperone BiP.
Acumulation of bile pigment in bile canaliculus is a subtype of bile pigment deposition: The aggregation of bile pigmentin a particular location in a bile canaliculus. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
acumulation of bile pigment in bile canaliculus [Cholestasis]
Acumulation of bile pigment in hepatocyte is a subtype of bile pigment deposition: The aggregation of bile pigmentin a particular location in a hepatocyte. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
acumulation of bile pigment in hepatocyte [Cholestasis]
XBP1 activation by IRE1 is a subtype of activation of transcription factor: A process that changes the activity of XBP1 (X-Box Binding Protein 1) to be higher by IRE1. This entity is a specific course-dependent process. This process is dependent on the ERAD process and can constitute the course of ER stress.
The XBP1 gene is transcribed to yield mRNA, the mRNA is spliced to yield Xbp(s) mRNA, and the mRNA is translated to yield protein.
XBP1 activation by IRE1 [ER stress - ERAD]
Negative regulation of bile acid and bile salts export from the hepatocyte to bile tube is a subtype of negative regulation of transport: A process that stops, prevents, or reduces the frequency, rate or extent of bile acid and bile salts export from the hepatocyte to the bile tube. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
Export into the canaliculus is mediated by the BSEP (bile salt export pump, ABCB11) . Rifampicin, bosentan, and troglitazone directly inhibit bile salt export pump (BSEP).
negative regulation of bile acid and bile salts export from the hepatocyte to bile tube [Cholestasis]
Negative regulation of transport is a subtype of negative regulation process: Any process that stops, prevents, or reduces the frequency, rate or extent of the directed movement of substances (such as macromolecules, small molecules, ions) into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
Bile secretion is a subtype of moving A to the outside of B: A process of the release of the bile to the outside of the liver.
IRE1 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the IRE1 (Inositol-requiring transmembrane kinase/endonuclease). IRE1 generally plays a endoplasmic reticulum membrane stress sensor role. This entity is a specific course-dependent process. This process is dependent on ERAD and can constitute the course of ER stress.
IRE1 signaling (primitive) [ER stress - ERAD]
IRE1 activation is a subtype of molecular activation: A process that changes the activity of the IRE1 to be higher. This entity is a specific course-dependent process. This process is dependent on ERAD and can constitute the course of ER stress.
IRE1 activation is a subtype of molecular activation: A process that changes the activity of the IRE1 to be higher. This process is dependent on the refolding and can constitute the course of ER stress.
IRE1 activation is a subtype of molecular activation: A process that changes the activity of the IRE1 to be higher. This process is dependent on the apoptosis and can constitute the course of ER stress.
IRE1 activation is a subtype of molecular activation: A process that changes the activity of the IRE1 to be higher. This process is dependent on the inflammation and can constitute the course of ER stress.
IRE1 activation [ER stress - inflammation]
XBP1 activation by IRE1 is a subtype of activation of transcription factor: A process that changes the activity of XBP1 (X-Box Binding Protein 1) to be higher by IRE1. This process is dependent on the refolding and can constitute the course of ER stress.
XBP1 activation by IRE1 [ER stress - refolding]
XBP1 activation by IRE1 is a subtype of activation of transcription factor: A process that changes the activity of XBP1 (X-Box Binding Protein 1) to be higher by IRE1. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
ATF6 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the ATF6 (activating transcription factor 6). ATF6 generally plays a endoplasmic reticulum membrane stress sensor role. This process is dependent on ERAD and can constitute the course of ER stress.
ATF6 signaling (primitive) [ER stress - ERAD]
Bile secretion to bile canaliculus is a subtype of bile secretion: A process that of the release from one side of a hepatocyte plasma membrane to a bile canaliculus. Bile canaliculi are the thin tubes formed by hepatocyte membranes.
Bile acid and bile salt transport to hepatocyte is a subtype of bile acid and bile salt transport: A process that transports bile acid and bile salts within a hepatocyte by means of some agent such as a transporter or pore.
bile acid and bile salt transport to hepatocyte
A family of transmembrane proteins that usually function as dimers to hydrolyze ATP, which permits them to transport a wide variety of substrates across cellular membranes. These proteins consist of two distinct domains, a transmembrane domain and a nucleotide-binding domain. ATP binding is required for both dimerization and transporter activity.
Contraction of bile canaliculus is a subtype of contraction: A process that generates the directed movement in which the bile canaliculus decreases in volume.
ERAD related gene expression by XBP1s is a subtype of gene expression: The process in which a gene sequence is converted into a mature ER-associated degradation (ERAD) gene product or products (proteins or RNA) by XBP1s. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
ERAD related gene expression byXBP1s [ER stress]
OATP transporters are a critical factor controlling the uptake of glibenclamide by the liver. GLB is a substrate for OATP2B1 and OATP1B1, which are expressed at the sinusoidal membrane of hepatocytes.
rifampicin, cyclosporine A, rifamycin SV, bosentan, troglitazone, erythromycin estolate, and glibenclamide inhibit Bsep in rats
The directed movement of drugs into hepatocyte vascular side (sinusoidal side) membrane by OATP. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
importing substance into hepatocyte vascular side (sinusoidal side) membrane by OATP [Cholestasis]
Extracts misfolded glycoproteins, but not glycoproteins undergoing productive folding, from the calnexin cycle. It is directly involved in endoplasmic reticulum-associated degradation (ERAD) and targets misfolded glycoproteins for degradation in an N-glycan-independent manner, probably by forming a complex with SEL1L. It has low mannosidase activity, catalyzing mannose trimming from Man8GlcNAc2 to Man7GlcNAc2.
ERdj5 is required as a disulfide reductase for degradation of misfolded proteins in the ER. Science 321: 569-572, 2008.
EDEM -ERAD promoting factor (canonical)[ER stress -ERAD]
Hyperfunctioning of glutathione conjugates excretion from hepatocyte is a subtype of hyperfunctioning: A process that performs an excessive excretion of the glutathione conjugates from the hepatocyte.
hyperfunctioning of glutathione conjugates excretion from hepatocyte
Converting cell type is a subtype of converting type: A process that changes the type of the cell.
Changing permeability is a subtype of changing quality: A process that changes the temperature of the object.
Changing size is a subtype of changing quality: A process that changes the size of the object.
Increasing canalicular membrane permeability is a subtype of increasing membrane permeabilization: A process that changes the permeability of the canalicular membrane to be higher.
increasing canalicular membrane permeability
An estrogen that has formula C18H22O2. This compound might be participated in the process involved in the course of cholestasis.
Hyperfunction of glutathione export from hepatocyte is a subtype of hyperfunction of transport: A process that performs an excesssive export of the glutathione from the hepatocyte.
hyperfunction of glutathione export from hepatocyte
A process in which a signal to XBP1 is transduced by the IRE1. This entity is a specific course-dependent process. This process is dependent on ERAD and can constitute the course of ER stress.
Receiving abnormal protein signal by IRE1 is a subtype of receiving signal: A process that recognizes another object and changes into an abnormal protein (e.g., misfolded protein, etc.) signal by IRE1. This process is dependent on the ERAD and can constitute the course of ER stress.
receiving abnormal protein signal by IRE1 [ER stress - ERAD]
Hyperfunction of glutathione export from hepatocyte is a subtype of hyperfunction of transport: A process that performs an excesssive export of the glutathione from the hepatocyte. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
hyperfunction of glutathione export from hepatocyte [Glutathione depletion]
A role played by the entity which regulatess OATP bile acid transport process.
Bile tube occlusion is a subtype of occlusion: Obstruction or a closure of bile tube.
Increasing bile level is a subtype of increasing quantity: A process that changes the amount of bile to be higher.
Increasing bile concentration in blood is a subtype of increasing concentration: A process that changes the concentration of the bile in the blood to be higher.
Refolding promoting gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature refolding inducing gene product or products (proteins or RNA) . This entity is a specific course-dependent process. This process can constitute the course of ER stress.
refolding promoting gene expression [ER stress]
Increasing vomume of bile canaliculus is a subtype of increasing volume: A process that changes the volume of the bile canaliculus to be higher.
Hyperfunction of protein unfolding is a subtype of hyperfunctioning: A process that performs an excesssive protein unfolding.
A process that performs an excesssive moving phenobarbital to the inside of liver. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
hyperfunction of moving phenobarbital to the inside of liver [Ground glass appearance]
ATF4 gene expression by eIF2a is a subtype of gene expression: The process in which a gene sequence is converted into a mature ATF4 gene product or products (proteins or RNA) by eIF2a. This process is dependent on the apoptosis and can constitute the course of ER stress.
ATF4 gene expression by eIF2a [ER stress - apoptosis]
Chop expession by ATF4 is a subtype of gene expression by transcriptional factor: The process in which a sequence of the Chop is converted into a mature gene product or products (proteins or RNA) by ATF4. This process is dependent on the apoptosis and can constitute the course of ER stress.
Chop expression by ATF4 [ER stress] [ER stress - apoptosis]
Nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. SHP-1 represses expression of CYP7A1 by inhibiting the activity of liver receptor homolog 1 (LRH-1), an orphan nuclear receptor known to regulate CYP7A1 expression.
Genes encoding for organic anion uptake (NTCP, OATPs), canalicular export (BSEP, MRP2) and alternative basolateral export (MRP3, MRP4) in liver are regulated by hepatocyte nuclear factors (HNF1, 3, 4) and nuclear (orphan) receptors (e.g., FXR, PXR, CAR, RAR, LRH-1, SHP, GR). Bile acids, proinflammatory cytokines, hormones and drugs mediate causative and adaptive transporter changes at a transcriptional level by interacting with these nuclear factors and receptors.
Ubiquitination of IkB is a subtype of protein ubiquitination: The process in which one or more ubiquitin groups are added to IkB.
PERK - signaling factor (canonical)[ER stress - apotosis]
PERK - signaling factor (canonical)[ER stress - Refolding]
PERK - signal sensor (canonical)[ER stress - apotosis]
Receiving abnormal protein signal by PERK is a subtype of receiving signal: A process that recognizes another object and changes into an abnormal protein (e.g., misfolded protein, etc.) signal by PERK. This process is dependent on the apoptosis and can constitute the course of ER stress via apoptosis.
receiving abnormal protein signal by PERK [ER stress - apoptosis]
Positive regulation of bile export is a subtype of positive regulation process: A process that that activates or increases the frequency, rate or extent of bile acid secretion.
Negative regulation of bile acid and bile salts export from the hepatocyte to bile tube is a subtype of negative regulation of transport: A process that stops, prevents, or reduces the frequency, rate or extent of bile acid and bile salts export from the hepatocyte to the bile tube. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
negative regulation of bile acid and bile salts export from the hepatocyte to bile tube [Glutathione depletion]
Cholestasis is a subtype of stagnating: A process that changes the bile flow to be slower due to obstruction. This entity is a specific course-dependent process. This process can constitute the course of glutathione depletion.
PERK-Nrf2 mediated pathway is a subtype of PERK signaling (integrated pathway): Sequence of linked reactions, which has PERK signaling and gene regulation pathway.
PERK-Nrf2 mediated pathway (integrated pathway)
A process that changes the activity of the NRF2 to be higher by PERK. This entity is a specific course-dependent process. This process can constitute the course of PERK - NRF2 pathway.
NRF2 activation by PERK [PERK - NRF2 pathway]
Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival.
Dissociation of Nrf2-Keap1 complex is a subtype of detaching: A process that disaggregates a Nrf2-Keap1 complexe into Nrf2 and Keap1.
Dissociation of Nrf2-Keap1 complex by Perk is a subtype of detaching: A process that disaggregates a Nrf2-Keap1 complex into Nrf2 and Keap1 by Perk. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
PERK activation->dissociation of Nrf2/Keap in ER stress
PERK-dependent phosphorylation triggers dissociation of Nrf2/Keap1 complexes and inhibits reassociation of Nrf2/Keap1 complexes in vitro.
dissociation of Nrf2-Keap1 complex by PERK [ER stress]
A process that changes the activity of the NRF2 to be higher by PERK. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
PERK-NRF2 mediated pathway is a subtype of PERK signaling (integrated pathway): Sequence of linked reactions, which has PERK-NRF2 signaling and gene regulation pathway. This pathway is a specific course-dependent process. This process can constitute the course of ER stress.
Receiving abnormal protein signal by PERK is a subtype of receiving signal: A process that recognizes another object and changes into an abnormal protein (e.g., misfolded protein, etc.) signal by PERK. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
receiving abnormal protein signal by PERK [ER stress]
A process in which a signal to NRF2 is transduced PERK. This entity is a specific course-dependent process. This process can constitute the course of PERK - eIF2A pathway.
PERK signaling to Nrf2 [PERK - eIF2A pathway]
A process in which a signal to NRF2 is transduced PERK . This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Antioxidant gene expression by NRF2 is a subtype of gene expression: The process in which an antioxidant gene sequence is converted into a mature antioxidant gene product or products (proteins or RNA) by NRF2. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
antioxidant gene expression by NRF2 [ER stress]
NRF2 - transcriptional regulator (canonical)[ER stress]
Any process that activates or increases the frequency, rate or extent of cellular response to oxidative stress. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
positive regulation of cellular response to oxidative stress [ER stress]
Oxidation-antioxidtion inbalance is a subtype of imbalance: A process that lacks a balance between oxidation and anti-oxidation that inhibits oxidation. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
oxidation-antioxidtion inbalance [ER stress]
Oxidation-antioxidtion inbalance is a subtype of imbalance: A process that lacks a balance between oxidation and anti-oxidation that inhibits oxidation.
Receiving oxidative signal by PERK is a subtype of receiving signal: A process that recognizes another object and changes into a oxidative signal by PERK. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
receiving oxidative signal by PERK [ER stress]
PERK activation is a subtype of Molecular activation: A process that changes the activity of PERK to be higher. This process is dependent on the antioxidation and can constitute the course of ER stress.
PERK activation [ER stress - antioxidation]
Enabling translation is a subtype of enabling: A process that sets conditions for translation to work correctly. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
This entity refers to the process of restarting translation. During protein refolding, it is known that a translation attenuation is occurred temporarily to reduce the production of new proteins.
The process of removing one or more phosphoric (ester or anhydride) residues from the eIF2a. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Gene expression patheway dependent molecule is a subtype of system dependeny functional molecule. This entity is dependent on a gene expresion system for functioning.
gene expression patheway dependent molecule
eIF2a gene regulation pathway is a subtype of gene regulation pathway: Sequence of reactions to regulate translation of genes by eIF2a.
Regulation of translation by eIF2a is a subtype of regulation of translation: A process that modulates the frequency, rate or extent of eIF2 alpha mediated translation. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
regulation of translation by eIF2a [ER stress]
Positive regulation of uORF dependent gene expression is a subtype of positive regulation of gene expression: A process that modulates the frequency, rate or extent of uORF dependent gene expression.
positive regulation of uORF dependent gene expression
Positive regulation of uORF dependent gene expression is a subtype of positive regulation of gene expression: A process that modulates the frequency, rate or extent of uORF dependent gene expression. This entity is a specific eIF2a translational system depedent.
positive regulation of uORF dependent gene expression [eIF2a [translation regulation]
Degradation of I-kappaB is a subtype of protein catabolic process: A process of the chemical reactions resulting in the breakdown of inhibitor of kappa B (I-kappaB) protein
Bile acid accumulation in hepatocyte is a subtype of accumulation of substances in a biological object: A process that keeps bile acid within the hepatocute in the liver (intrahepatic). This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
Bile acid accumulation in hepatocyte [Glutathione depletion]
Refolding promoting gene expression by XBP1s is a subtype of gene expression: The process in which a gene sequence is converted into a mature refolding inducing gene product or products (proteins or RNA) by XbP1s . This entity is a specific course-dependent process. This process can constitute the course of ER stress.
refolding promoting gene expression by XBP1s [ER stress]
A process in which a signal to XBP1 is transduced by the IRE1. This process is dependent on the refolding and can constitute the course of ER stress.
IRE1 signaling to XBP1 [ER stress - refolding]
Any process that modulates the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of proteins by the translation of mRNA or circRNA by eIF2A in the course of ER stress. This process is dependent on the translation attenuation and can constitute the course of ER stress.
regulation of translation by eIF2a [ER stress - translation attenuation]
Gene expression by NRF2 is a subtype of Gene expression by transcriptional regulator: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) by NRF2.
Gene expression by NRF2 is a subtype of Gene expression by transcriptional regulator: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) by NRF2. This entity is a specific course-dependent process. This process can constitute the course of PERK - NRF2 pathway.
gene expression by NRF2 [PERK - NRF2 pathway]
Gene expression by NRF2 is a subtype of Gene expression by transcriptional regulator: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) by NRF2. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Inflammatory cytokine gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature inflammatory cytokine gene product or products (proteins or RNA). This entity is a specific course-dependent process. This process can constitute the course of ER stress.
inflammatory cytokine gene expression [ER stress]
Gene expression by CHOP (DDIT3, GADD153) is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) by CHOP (DDIT3, GADD153). This process is dependent on the apoptosis and can constitute the course of ER stress.
gene expression by CHOP (DDIT3, GADD153) [ER stress - apoptosis]
NFKB - transcriptional regulator (canonical)[ER stress - inflammation]
Gene expression bu NF-kappaB is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) by NF-kappaB.
I-kappaB phosphorylation is a subtype of phosphorylation: The process of introducing a phosphate group into an inhibitor of kappa B (I-kappaB) protein. Phosphorylation of I-kappaB targets I-kappaB for ubiquitination and proteasomal degradation, thus releasing bound NF-kappaB dimers, which can translocate to the nucleus to bind DNA and regulate transcription. This entity is a specific course-dependent process. This process can constitute the course of NfKB pathway.
XBP1 splicing is a subtype of removing: The process of removing sections of the XBP1 RNA transcript to remove sequences. This process is dependent on the inflammation and can constitute the course of ER stress.
XBP1 splicing [ER stress - inflammation]
A series of molecular signals transduced with the regulation of transcription of target genes by NF-kappaB. In a resting state, NF-kappaB dimers are bound to I-kappaB proteins, sequestering NF-kappaB in the cytoplasm. Phosphorylation of I-kappaB targets I-kappaB for ubiquitination and proteasomal degradation, thus releasing the NF-kappaB dimers, which can translocate to the nucleus to bind DNA and regulate transcription.
Inflammatory gene expression by NF-kappa B is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) related to the inflammation by NF-kappa B. This process is dependent on the IRE1-TRAF2-NfkB pathway mediated inflammation and can constitute the course of ER stress.
inflammatory gene expression by NF-kappa B [ER stress - inflammation - IRE1-TRAF-NfkB pathway]
Ubiquitination of IkB is a subtype of protein ubiquitination: The process in which one or more ubiquitin groups are added to IkB. This entity is a specific course-dependent process. This process can constitute the course of NfKB pathway.
Degradation of I-kappaB is a subtype of protein catabolic process: A process of the chemical reactions resulting in the breakdown of inhibitor of kappa B (I-kappaB) protein This entity is a specific course-dependent process. This process can constitute the course of NfKB pathway.
NF-kappaB transport into nucleus is a subtype of nuclear transport: A process that of the directed movement of NF-kappaB from the cytoplasm to the nucleus. This entity is a specific course-dependent process. This process can constitute the course of NfKB pathway.
Translocation of NF-kappaB [NfKB pathway]
IKK activation is a subtype of molecular activation: A process that changes the activity of the IKK (kappaB Kinase) to be higher.
IKK activation is a subtype of molecular activation: A process that changes the activity of the IIKK (kappaB Kinase) to be higher. This entity is a specific course-dependent process. This process can constitute the course of NfKB pathway.
NF-kappaB activation is a subtype of transcription factor activation: A process that changes the activity of the NF-kappaB to be higher.
NF-kappaB activation is a subtype of transcription factor activation: A process that changes the activity of the NF-kappaB to be higher. This entity is a specific course-dependent process. This process can constitute the course of NfKB pathway.
Regulation of gene expression by NfKB is a subtype of regulation of gene expression: A process that stops, prevents, or reduces the frequency, rate or extent of gene expression by NfkB.
Regulation of gene expression by NfKB is a subtype of regulation of gene expression: A process that stops, prevents, or reduces the frequency, rate or extent of gene expression by NfkB. This entity is a specific course-dependent process. This process can constitute the course of NfKB pathway.
regulation of gene expression by NfKB [NfKB pathway]
Binding of NF-kappaB and I-kappaB in cytosol is a subtype of binding: The selective interaction of a inhibitory-kappaB (I-kappaB/IKB) protein with NF-kappaB. In the resting state, NF-kappaB dimers are bound to I-kappaB proteins, sequestering NF-kappaB in the cytoplasm.
http://purl.obolibrary.org/obo/IEV_0000214 (obsolete)
Binding of NF-kappaB and I-kappaB in cytosol
ABCC4 (canonical)[Glutathione depletion]
Forming disulfide bond 2 is a subtype of binding: The interaction between molecules with interchain disulfide bonds. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
The selective interaction of the transcription factor NF-kappaB with specific molecules in the cytoplasm, thereby inhibiting its translocation into the nucleus. This entity is a specific course-dependent process. This process can constitute the course of NfKB pathway.
cytoplasmic sequestering of NF-kappaB [NfKB pathway]
The selective interaction of a inhibitory-kappaB (I-kappaB/IKB) protein with NF-kappaB. In the resting state, NF-kappaB dimers are bound to I-kappaB proteins, sequestering NF-kappaB in the cytoplasm. This entity is a specific course-dependent process. This process can constitute the course of NfKB pathway.
Binding of NF-kappaB and I-kappaB in cytosol [NfkB pathway]
Dissociation of NF-kappaB -I-kappaB is a subtype of detaching: A process that disaggregates a NF-kappaB-I-kappaB to NF-kappaB dimers and I-kappaB. In a resting state, NF-kappaB dimers are bound to I-kappaB proteins, sequestering NF-kappaB in the cytoplasm. Phosphorylation of I-kappaB targets I-kappaB for ubiquitination and proteasomal degradation, thus releasing the NF-kappaB dimers, which can translocate to the nucleus to bind DNA and regulate transcription. This entity is a specific course-dependent process. This process can constitute the course of NfKB pathway.
dissociation of NF-kappaB - IkappaB [NfKB pathway]
ABCC5 (canonical)[Glutathione depletion]
PERK-NFkB pathway is a subtype of PERK signaling (integrated pathway): Sequence of linked reactions, which has PERK signaling and gene regulation pathway. This pathway is dependent on the inflammation and can constitute the course of ER stress.
PERK-NFkB pathway [ER stress - inflammation]
PERK-eIF2a-NFkB pathway is a subtype of PERK-eIF2a signaling: Sequence of linked reactions, which has PERK-eIF2a signaling and gene regulation by NF-kappa B. This pathway is dependent on the inflammation and can constitute the course of ER stress.
PERK-eIF2a-NFkB pathway [ER stress - inflammation]
Both the IRE1α and PERK branches of the UPR can lead to activation of the NF-κB-IKK pathway. This pathway also plays a critical role in the induction of multiple inflammatory mediators and has been implicated in insulin resistance.
phosphorylated eIF2α attenuates general mRNA translation, During translational attenuation, IκB, an inhibitor of NF-κB, is depleted (due to its short half-life) to activate NF-κB.
IRE1-TRAF2-NFkB signal transduction pathway is a subtype of IRE1 signaling (integrated pathway): Sequence of linked reactions, which has IRE1-TRAF2 signaling and gene regulation by NF-kappaB. This pathway is dependent on the inflammation and can constitute the course of ER stress.
IRE1-TRAF2-NFkB signal transduction pathway [ER stress - inflammation]
NF-kB was activated by ER stress-inducing agents, thapsigargin and tunicamycin. The activation was inhibited by a dominant-negative IRE1. In addition, a dominant-negative TRAF2 also suppressed the activation of NF-kB by ER stress. These results suggest that ER stress-induced NF-kB activation is also mediated by the IRE1- TRAF2 pathway, as well as JNK activation.
Result indicates that the RNase domain of IRE1 in the C-terminus is necessary for the binding of IRE1 with TRAF2, and that ER stress-induced NF-kB activation is dependent on not only the interaction between IRE1 and TRAF2, but also the kinase activity of IRE1.
IRE-1 directly triggers IκB kinase and as such IκB phosphorylation, in a TNF receptor associated factor (TRAF)-2 dependent manne
ATF6-NFkB signal transduction pathway is a subtype of ATF6 signaling (integrated pathway): Sequence of linked reactions, which has ATF6 signaling and gene regulation by NF-kappaB. This process is dependent on positive inflammation and can constitute the course of ER stress.
ATF6-NFkB signal transduction pathway [ER stress - inflammation]
The ATF6 branch of the UPR has also been linked to NF-κB-IKK signaling, suggesting that specific inflammatory triggers may signal through different branches of the UPR.
PERK-eIF2a signaling is a subtype of PERK signaling (integrated pathway): Sequence of linked reactions, which has PERK-eIF2a signaling and gene regulation pathway. This pathway is dependent on the inflammation and can constitute the course of ER stress.
PERK-eIF2a signaling [ER stress - inflammation]
NF-kappaB activation is a subtype of transcription factor activation: A process that changes the activity of the NF-kappaB to be higher. This process is dependent on the inflammation and can constitute the course of ER stress.
CHOP Knock Down resulted in reduced cytokine-induced NF-κB activity and expression of key NF-κB target genes involved in apoptosis and inflammation, including iNOS, FAS, IRF-7, IL-15, CCL5 and CXCL10. This was due to decreased IκB degradation and p65 translocation to the nucleus
NF-kappaB activation [ER stress - inflammation]
Decreasing I-kappaB production is a subtype of decreasing production quantity of protein: A process that changes the quantity of the Iinhibitor of kappa B (I-kappaB) to be lower.
Decreasing I-kappaB production is a subtype of decreasing production quantity of protein: A process that changes the quantity of the Iinhibitor of kappa B (I-kappaB) to be lower. This process is dependent on the Perk-eIF2a-NfkB pathway mediated inflammation and can constitute the course of ER stress.
decreasing I-kappaB production [ER stress - inflammation -Perk-eIF2a-NfkB]
Activation of PERK and concomitant translational inhibition leads to a disequilibrium in the ratio of the short-lived IκB protein (inhibitor of NF-κB) to the longer-lived NF-κB protein, resulting in activation of NF-κB, independent of IκB phosphorylation
inhibitor of NF-kappaB [ER stress - inflammation]
I-kappaB -NfkB inhibitor [ER stress - inflammation]
A role played by the entity which enables the energy-independent passage of cations across a lipid bilayer down a concentration gradient.
NF-kappaB transport into nucleus is a subtype of nuclear transport: A process that of the directed movement of NF-kappaB from the cytoplasm to the nucleus. This process is dependent on the inflammation and can constitute the course of ER stress.
Translocation of NF-kappaB [ER stress - inflammation]
Inflammatory gene expression by NF-kappa B via PERK is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) related to the inflammation by NF-kappa B via PERK. This process is dependent on the inflammation and can constitute the course of ER stress.
inflammatory cytokine gene expression by NF-kappa B via PERK [ER stress - inflammation]
Inflammatory cytokine gene expression via JNK is a subtype of gene expression: The process in which a gene sequence is converted into a mature inflammatory cytokine gene product or products (proteins or RNA) via JNK pathway. This process is dependent on the inflammation and can constitute the course of ER stress.
inflammatory cytokine gene expression via JNK [ER stress - inflammation]
NF-kappaB activation is a subtype of transcription factor activation: A process that changes the activity of the NF-kappaB to be higher. This process is dependent on the IRE1-TRAF2-IkB-NfkB pathway mediated inflammation and can constitute the course of ER stress.
NF-kappaB activation [ER stress - inflammation - IRE1-TRAF2-IkB-NfkB pathway]
I-kappaB phosphorylation is a subtype of phosphorylation: The process of introducing a phosphate group into an inhibitor of kappa B (I-kappaB) protein. Phosphorylation of I-kappaB targets I-kappaB for ubiquitination and proteasomal degradation, thus releasing bound NF-kappaB dimers, which can translocate to the nucleus to bind DNA and regulate transcription. This process is dependent on the IRE1-NfkB pathway mediated inflammation and can constitute the course of ER stress.
I-kappaB phosphorylation [ER stress - inflammation - IRE1-NfkB pathway]
Ubiquitination of IkB is a subtype of protein ubiquitination: The process in which one or more ubiquitin groups are added to IkB. This process is dependent on the IRE1-NfkB pathway mediated inflammation and can constitute the course of ER stress.
ubiquitination of IkB [ER stress - inflammation - IRE1-NfKB pathway]
Degradation of I-kappaB is a subtype of protein catabolic process: A process of the chemical reactions resulting in the breakdown of inhibitor of kappa B (I-kappaB) protein. This process is dependent on the IRE1-NfkB pathway mediated inflammation and can constitute the course of ER stress.
Inflammatory gene expression by NF-kappa B via IRE1 is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) related to the inflammation by NF-kappa B via IRE1. This process is dependent on the inflammation and can constitute the course of ER stress.
inflammatory cytokine gene expression by NF-kappa B via IRE1 [ER stress - inflammation]
Regulation of gene expression by NfKB is a subtype of regulation of gene expression: A process that stops, prevents, or reduces the frequency, rate or extent of gene expression by NfkB. This process is dependent on the PERK-eIF2a-NfkB pathway mediated inflammation and can constitute the course of ER stress.
regulation of gene expression by NfKB [ER stress - inflammation - PERK-eIF2a-NfkB pathway]
Regulation of gene expression by NfKB is a subtype of regulation of gene expression: A process that stops, prevents, or reduces the frequency, rate or extent of gene expression by NfkB. This process is dependent on the IRE1-TARF2-NfkB pathway mediated inflammation and can constitute the course of ER stress.
regulation of gene expression by NfKB [ER stress - inflammation - IRE1-Traf2-NfkB pathway]
Translocation of NF-kappaB from the Cytosol to the Nucleus is a subtype of nuclear transport: A process that of the directed movement of NF-kappaB from the cytoplasm to the nucleus. This process is dependent on the Perk-eIF2a-NfkB pathway mediated inflammation and can constitute the course of ER stress.
Translocation of NF-kappaB from the Cytosol to the Nucleus [ER stress - inflammation - Perk-eIF2a-NfkB pathway]
Translocation of NF-kappaB from the Cytosol to the Nucleus is a subtype of nuclear transport: A process that of the directed movement of NF-kappaB from the cytoplasm to the nucleus. This process is dependent on the IRE1-TRAF2-NfkB pathway mediated inflammation and can constitute the course of ER stress.
Translocation of NF-kappaB from the Cytosol to the Nucleus [ER stress - inflammation - IRE1-TRAF2-NfkB pathway]
TRAF2 activation by IRE1 is a subtype of molecular activation: A process that changes the activity of the TARF2 to be higher by IRE1. This process is dependent on the IRE1-TRAF2-IKK-NfkB pathway mediated inflammation and can constitute the course of ER stress.
TRAF2 activation by IRE1 [ER stress - inflammation - IRE1-TRAF2-IKK-NfkB pathway]
IRE-1 directly triggers IκB kinase and as such IκB phosphorylation, in a TNF receptor associated factor (TRAF)-2 dependent manner
IKK activation is a subtype of molecular activation: A process that changes the activity of the IIKK (kappaB Kinase) to be higher. This process is dependent on the IRE1-TRAF2-NfkB pathway mediated inflammation and can constitute the course of ER stress.
IKK activation [ER stress - inflammation - IRE1-TRAF2-NfkB pathway]
TRAF2 -IRE1 adaptor protein (canonical)[ER stress - inflammation -IRE1-NfkB]
TRAF2 activation by IRE1 is a subtype of molecular activation: A process that changes the activity of the TARF2 to be higher by IRE1. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
TRAF2 activation by IRE1 is a subtype of molecular activation: A process that changes the activity of the TARF2 to be higher by IRE1. This process is dependent on the IRE1-TRAF2-ASK-JNK pathway mediated inflammation and can constitute the course of ER stress.
TRAF2 activation by IRE1 [ER stress - inflammation - IRE1-TRAF2-ASK-JNK pathway]
IRE-1 also mediates phosphorylation of JNK in a TRAF2-ASK dependent pathway18, which was linked to insulin receptor substrate (IRS)-1 phosphorylation and the development of insulin resistance in type II diabetes
TRAF2 -IRE1 adaptor protein (canonical)[ER stress - inflammation -IRE1-JNK]
ASK activation is a subtype of molecular activation: A process that changes the activity of one of the ASK (apoptosis signal-regulating kinase) family to be higher. This process is dependent on the inflammation and can constitute the course of ER stress.
ASK activation [ER stress - inflammation]
IRE-1 also mediates phosphorylation of JNK in a TRAF2-ASK dependent pathway, which was linked to insulin receptor substrate (IRS)-1 phosphorylation and the development of insulin resistance in type II diabetes.
ASK activation is a subtype of molecular activation: A process that changes the activity of one of the ASK (apoptosis signal-regulating kinase) family to be higher. This entity is a specific course-dependent process. This process can constitute the course of IRE-TRAF2-ASK-JNK pathway.
ASK activation [IRE-TRAF2-ASK-JNK pathway]
ASK activation is a subtype of molecular activation: A process that changes the activity of one of the ASK （apoptosis signal-regulating kinase) family to be higher.
JNK activation is a subtype of molecular activation: A process that changes the activity of the JNK to be higher. This entity is a specific course-dependent process. This process can constitute the course of JNK pathway.
JNK activation is a subtype of molecular activation: A process that changes the activity of the JNK to be higher. This process is dependent on the IRE1-TRAF2-ASK-JNK pathway mediated inflammation and can constitute the course of ER stress.
JNK activation [ER stress - inflammation - IRE1-TRAF2-ASK-JNK pathway]
JNK activation is a subtype of molecular activation: A process that changes the activity of the JNK to be higher.
AP-1 activation is a subtype of AP-1 activation: A process that changes the activity of the AP-1 to be higher by JNK. This process is dependent on the IRE1-TRAF2-ASK-JNK pathway mediated inflammation and can constitute the course of ER stress.
AP-1 activation by JNK [ER stress - inflammation - IRE1-TRAF2-ASK-JNK pathway]
Inflammatory gene expression by XBP1s is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) related to the inflammation by XBP1s. This process is dependent on the inflammation and can constitute the course of ER stress.
inflammatory cytokine gene expression by XBP1s [ER stress - inflammation]
A process in which a signal to XBP1 is transduced by the IRE1. This process is dependent on the inflammation and can constitute the course of ER stress.
IRE1 signaling to XBP1 [ER stress - inflammation]
XBP1 activation by IRE1 is a subtype of activation of transcription factor: A process that changes the activity of XBP1 (X-Box Binding Protein 1) to be higher by IRE1. This process is dependent on the inflammation and can constitute the course of ER stress.
XBP1 activation by IRE1 [ER stress - inflammation]
Inflammatory gene expression by AP-1 is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) related to the inflammation by AP-1. This process is dependent on the inflammation and can constitute the course of ER stress.
inflammatory cytokine gene expression by AP-1 [ER stress - inflammation]
The IRE1a branch of the UPR is responsible for AP-1 activation. Genes tran- scribed by AP-1 include those encoding tumor necrosis factor (TNF), keratinocyte growth factor (KGF), granulo- cyte macrophage colony-stimulating factor (GM-CSF), in- terleukin (IL)-8, and certain cytokine receptors .
A process in which a signal to TRAF2 is transduced by the IRE1. This process is dependent on the IRE1-TRAF2-IKK-NfkB pathway mediated inflammation and can constitute the course of ER stress.
IRE1 signaling to TRAF2 [ER stress - inflammation - IRE1-TRAF2-IKK-NfkB pathway]
A process in which a signal to TRAF2 is transduced by the IRE1. This process is dependent on the IRE1-TRAF2-ASK-JNK pathway mediated inflammation and can constitute the course of ER stress.
IRE1 signaling to TRAF2 [ER stress - inflammation - IRE1-TRAF2-ASK-JNK pathway]
IRE1-XBP1 mediated pathway is a subtype of IRE1 signaling (integrated pathway): Sequence of linked reactions, which has IRE1 signaling and gene regulation by XBP1. This process is dependent on inflammation and can constitute the course of ER stress.
IRE1-XBP1 mediated pathway [ER stress - inflammation]
Translocation of NF-kappaB from the Cytosol to the Nucleus is a subtype of nuclear transport: A process that of the directed movement of NF-kappaB from the cytoplasm to the nucleus. This process is dependent on the ATF6-NfkB pathway mediated inflammation and can constitute the course of ER stress.
Translocation of NF-kappaB from the Cytosol to the Nucleus [ER stress - inflammation - ATF6-NfkB pathway]
ATF6 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the ATF6 (activating transcription factor 6). ATF6 generally plays a endoplasmic reticulum membrane stress sensor role. This process is dependent on the inflammation and can constitute the course of ER stress.
ATF6 signaling (primitive) [ER stress - inflammation]
PERK - stress sensor (canonical)[ER stress - translation attenuation]
Regulation of gene expression by NfKB is a subtype of regulation of gene expression: A process that stops, prevents, or reduces the frequency, rate or extent of gene expression by NfkB. This process is dependent on the ATF6-NfkB Pathway mediated inflammation and can constitute the course of ER stress.
regulation of gene expression by NfKB [ER stress - inflammation - ATF6-NfkB Pathway]
NF-kappaB activation is a subtype of transcription factor activation: A process that changes the activity of the NF-kappaB to be higher. This process is dependent on the ATF6-NfkB pathway mediated inflammation and can constitute the course of ER stress.
NF-kappaB activation [ER stress - inflammation - ATF6-NfkB]
Decreasing I-kappaB production is a subtype of decreasing production quantity of protein: A process that changes the quantity of the Iinhibitor of kappa B (I-kappaB) to be lower. This process is dependent on the ATF6-NfkB pathway mediated inflammation and can constitute the course of ER stress.
decreasing I-kappaB production [ER stress -inflmmation- ATF6-NfkB]
Inflammatory cytokine gene expression by NF-kappaB via ATF6 is a subtype of gene expression: The process in which a gene sequence is converted into a mature inflammatory cytokine gene product or products (proteins or RNA) by NF-kappaB via ATF6 signaling. This process is dependent on the inflammation and can constitute the course of ER stress.
inflammatory cytokine gene expression by NF-kappa B via ATF6 [ER stress - inflammation]
ATF6 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the ATF6 (activating transcription factor 6). ATF6 generally plays a endoplasmic reticulum membrane stress sensor role. This process is dependent on the ATF6-NfkB pathway mediated inflammation and can constitute the course of ER stress.
ATF6 signaling (primitive) [ER stress - inflammation - ATF6-NfkB pathway]
PERK - stress sensor (canonical)[ER stress - apotosis]
PERK - stress sensor (canonical)[ER stress - inflammation]
Receiving abnormal protein signal by PERK is a subtype of receiving signal: A process that recognizes another object and changes into an abnormal protein (e.g., misfolded protein, etc.) signal by PERK. This process is dependent on the inflammation and can constitute the course of ER stress via inflammation.
receiving abnormal protein signal by PERK [ER stress - inflammation]
PERK - signal sensor (canonical)[ER stress - inflammation]
A process in which a signal to eIF2a is transduced by PERK. This process is dependent on the inflammation and can constitute the course of ER stress.
PERK signaling to eIF2a [ER stress - inflammation]
PERK - signaling factor (canonical)[ER stress - inflammation]
XBP1 splicing is a subtype of removing: The process of removing sections of the XBP1 RNA transcript to remove sequences. This process is dependent on the refolding process and can constitute the course of ER stress.
A process that changes the activity of the eIF2a by PERK. This process is dependent on the inflammation and can constitute the course of ER stress.
changing activity of eIF2a by PERK [ER stress - inflammation]
Any process that stops, prevents, or reduces the frequency, rate or extent of I-Kappa B translation by eIF2a. This process is dependent on the inflammation and can constitute the course of ER stress.
attenuation of I-kappaB translation by eIF2a [ER stress - inflammation]
PERK activation is a subtype of Molecular activation: A process that changes the activity of PERK to be higher. This process is dependent on the inflammation and can constitute the course of ER stress.
PERK activation [ER stress - inflammation]
PERK dimerization is a subtype of protein dimerization: The formation of a PERK dimer, a macromolecular structure consists of two noncovalently associated identical or nonidentical subunits. This process is dependent on the inflammation and can constitute the course of ER stress.
PERK dimerization [ER stress - inflammation]
PERK - kinase (canonical)[ER stress - inflammation]
PERK - kinase (canonical)[ER stress - translation attenuation]
PERK - autophosphorylation kinase (canonical)[ER stress - translation attenuation]
PERK - autophosphorylation kinase (canonical)[ER stress - inflammation]
PERK - autophosphorylation kinase (canonical)[ER stress - apotosis]
PERK - autophosphorylation kinase (canonical)[ER stress - Refolding]
PERK - kinase (canonical)[ER stress - apotosis]
PERK - kinase (canonical)[ER stress - Refolding]
PERK - stress sensor (canonical)[ER stress - Refolding]
Dissociation of PERK:BIP heterodimer is a subtype of detaching: A process that disaggregates PERK-BIP heterodimers into BIP and PERK. This process is dependent on the inflammation and can constitute the course of ER stress.
Dissociation of PERK:BIP Heterodimer [ER stress - inflammation]
PERK dimerization is a subtype of protein dimerization: The formation of a PERK dimer, a macromolecular structure consists of two noncovalently associated identical or nonidentical subunits. This process is dependent on the apoptosis and can constitute the course of ER stress.
PERK dimerization [ER stress - apoptosis]
PERK dimerization is a subtype of protein dimerization: The formation of a PERK dimer, a macromolecular structure consists of two noncovalently associated identical or nonidentical subunits. This process is dependent on the refolding and can constitute the course of ER stress.
PERK dimerization [ER stress - refolding]
PERK autophosphorylation is a subtype of protein autophosphorylation: The phosphorylation by PERK of one or more of its own amino acid residues (cis-autophosphorylation), or residues on PERK (trans-autophosphorylation). This process is dependent on the inflammation and can constitute the course of ER stress.
PERK autophosphorylation [ER stress - inflammation]
PERK autophosphorylation is a subtype of protein autophosphorylation: The phosphorylation by PERK of one or more of its own amino acid residues (cis-autophosphorylation), or residues on PERK (trans-autophosphorylation). This process is dependent on the apoptosis and can constitute the course of ER stress.
PERK autophosphorylation [ER stress - apoptosis]
PERK autophosphorylation is a subtype of protein autophosphorylation: The phosphorylation by PERK of one or more of its own amino acid residues (cis-autophosphorylation), or residues on PERK (trans-autophosphorylation). This process is dependent on the refolding and can constitute the course of ER stress.
PERK autophosphorylation [ER stress - refolding]
XBP1 splicing is a subtype of removing: The process of removing sections of the XBP1 RNA transcript to remove sequences. This entity is a specific course-dependent process. This process is dependent on the ERAD process and can constitute the course of ER stress.
TRAF2 activation by IRE1 is a subtype of molecular activation: A process that changes the activity of the TARF2 to be higher by IRE1.
A duration quality of a process inhering in a bearer by virtue of the bearer's having slow progressive course of indefinite duration.
Regulation of translation by eIF2a is a subtype of regulation of translation: A process that modulates the frequency, rate or extent of eIF2 alpha mediated translation.
A series of molecular signals mediated by the endoplasmic reticulum stress sensor IRE1 (Inositol-requiring transmembrane kinase/endonuclease). This process is dependent on the apoptosis that can constitute the course of ER stress.
A series of molecular signals mediated by the endoplasmic reticulum stress sensor IRE1 (Inositol-requiring transmembrane kinase/endonuclease). This process is dependent on the inflammation via IRE1-XBP1 pathway that can constitute the course of ER stress.
IRE1 pathway [ER stress - inflammation - IRE1-XBP1 pathway]
A series of molecular signals mediated by the endoplasmic reticulum stress sensor IRE1 (Inositol-requiring transmembrane kinase/endonuclease). This process is dependent on the inflammation that can constitute the course of ER stress.
A series of molecular signals mediated by the endoplasmic reticulum stress sensor IRE1 (Inositol-requiring transmembrane kinase/endonuclease). This process is dependent on the inflammation via IRE1-JNK pathway that can constitute the course of ER stress.
IRE1 pathway [ER stress - inflammation - IRE1-JNK pathway]
A series of molecular signals mediated by the endoplasmic reticulum stress sensor IRE1 (Inositol-requiring transmembrane kinase/endonuclease). This process is dependent on the inflammation via IRE1-NfkB pathway that can constitute the course of ER stress.
IRE1 pathway [ER stress - inflammation - IRE1-NfkB pathway]
PERK dimer (canonical)[ER stress - Refolding]
PERK dimer (canonical)[ER stress - inflammation]
PERK dimer (canonical)[ER stress - apotosis]
PERK dimer (canonical)[ER stress - translation attenuation]
Dissociation of IRE1:BIP heterodimer is a subtype of detaching: A process that disaggregates IRE-1-BIP heterodimers into BIP and IRE1. This process is dependent on the inflammation and can constitute the course of ER stress.
Dissociation of IRE1:BIP Heterodimer [ER stress - inflammation]
IRE - stress sensor (canonical)[ER stress - inflammation]
Receiving abnormal protein signal by IRE1 is a subtype of receiving signal: A process that recognizes another object and changes into an abnormal protein (e.g., misfolded protein, etc.) signal by IRE1. This process is dependent on the inflammation and can constitute the course of ER stress.
receiving abnormal protein signal by IRE1 [ER stress - inflammation]
Receiving abnormal protein signal by IRE1 is a subtype of receiving signal: A process that recognizes another object and changes into an abnormal protein (e.g., misfolded protein, etc.) signal by IRE1. This process is dependent on the IRE1-TRAF2-ASK-JNK pathway mediated inflammation and can constitute the course of ER stress.
receiving abnormal protein signal by IRE1 [ER stress - inflammation - IRE1-TRAF2-ASK-JNK pathway]
Receiving abnormal protein signal by IRE1 is a subtype of receiving signal: A process that recognizes another object and changes into an abnormal protein (e.g., misfolded protein, etc.) signal by IRE1. This process is dependent on the IRE1-TRAF2-IKK-NfkB pathway mediated inflammation and can constitute the course of ER stress.
receiving abnormal protein signal by IRE1 [ER stress - inflammation - IRE1-TRAF2-IKK-NfkB pathway]
IRE1 - signal sensor (canonical)[ER stress - inflammation]
IRE1 - signaling factor (canonical)[ER stress - inflammation]
IRE1 - signaling factor (canonical)[ER stress -ERAD]
IRE1 - signaling factor (canonical)[ER stress - inflammation -Xbp1]
IRE1 - signaling factor (canonical)[ER stress - inflammation -TRAF2]
Receiving abnormal protein signal by IRE1 is a subtype of receiving signal: A process that recognizes another object and changes into an abnormal protein (e.g., misfolded protein, etc.) signal by IRE1. This process is dependent on the IRE1-XBP1 pathway mediated inflammation and can constitute the course of ER stress.
receiving abnormal protein signal by IRE1 [ER stress - inflammation - IRE1-XBP1 pathway]
phosphorylated eIF2A - translation initiation inhibitor [ER stress - inflammation]
P-EIF2A - translation initiation inhibitor (canonical)[ER stress - inflammation]
Calreticulin is a multifunctional protein that acts as a major Ca(2+)-binding (storage) protein in the lumen of the endoplasmic reticulum. It is also found in the nucleus, suggesting that it may have a role in transcription regulation.
CALR - chaperone [ER stress -Refolding [persist]]
CALRETICULIN - chaperone (canonical)[ER stress -Refolding [persist]]
Calnexin and calreticulin promote the efficient folding of glycoproteins by: (1) stabilizing folding events or slowing the folding process in a domain specific manner; (2) preventing aggregation and turnover; (3) retaining nonnative substrates in the ER to support additional attempts for proper folding; (4) facilitating the formation of disulfide bond formation through their association with the oxidoreductase ERp57 ; (5) perhaps facilitating Pro isomerization through association with the PPIase CypB
ATF6 - transcriptional factor (canonical)[ER stress - Refolding]
ATF6 - stress sensor (canonical)[ER stress - Refolding]
ATF6 - signaling factor (canonical)[ER stress - Refolding]
ATF6 - signaling factor (canonical)[ER stress - inflammation]
Dissociation of ATF6:BIP heterodimer is a subtype of detaching: A process that disaggregates ATF6-BIP heterodimers into BIP and ATF6. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Dissociation of ATF6-alpha:BIP Complex [ER stress]
Dissociation of ATF6:BIP heterodimer is a subtype of detaching: A process that disaggregates ATF6-BIP heterodimers into BIP and ATF6. This process is dependent on the refolding and can constitute the course of ER stress.
Dissociation of ATF6-alpha:BIP Complex [ER stress - refolding]
Bip-unfolded protein is a subtype of a molecular complex. This entity has sub-parts of molecules: BIP/GRP78, and an unfolded protein. This entity can participate in the infmallation of ER stress via PERK pathway.
Bip-unfolded protein complex 1 [ER stress - refolding]
Bip-unfolded protein is a subtype of a molecular complex. This entity has sub-parts of molecules: BIP/GRP78, and an unfolded protein. This entity can participate in the protein refolding of ER stress.
Bip-Unfolded Protein complex 2 [ER stress - refolding]
Bip-unfolded protein is a subtype of a molecular complex. This entity has sub-parts of molecules: BIP/GRP78, and an unfolded protein. This entity can participate in the inflammation of ER stress via IRE1 pathway.
Bip-unfolded protein complex 3 [ER stress - inflammation]
ATF6 mediated proapoptic gene production pathway is a subtype of ATF6 signaling (integrated pathway): Sequence of linked reactions, which has ATF6 signaling and gene regulation pathway. This process is dependent on positive regulation of apoptosis and can constitute the course of ER stress.
ATF6 mediated proapoptic gene production pathway [ER stress - apoptosis]
ATF6 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the ATF6 (activating transcription factor 6). ATF6 generally plays a endoplasmic reticulum membrane stress sensor role. This process is dependent on the apoptosis and can constitute the course of ER stress.
ATF6 signaling (primitive) [ER stress - apoptosis]
ATF6 - signaling factor (canonical)[ER stress - apotosis]
ATF6 activation is a subtype of molecular activation: A process that changes the activity of the ATF6 (Activating Transcription Factor 6) to be higher. This process is dependent on the apoptosis and can constitute the course of ER stress.
Refolding gene expression by ATF6 is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) related to the apoptosis by ATF6. This process is dependent on the apoptosis and can constitute the course of ER stress.
apoptotic gene expression by ATF6 [ER stress - apoptosis]
These findings support the idea that PERK/ATF6 cross-talk is a primary driver of CHOP expression within the liver ( A previous study of CHO and COS-1 cell lines suggested that ATF6 can contribute to CHOP expression by an ER-stress element situated in the CHOP promoter (Ma et al., 2002 blue right-pointing triangle). We addressed the role played by ATF6 in CHOP expression in Hepa1-6 cells by depleting ATF6 using shRNA, followed by treatment with 2 μM tunicamycin. Loss of ATF6 led to reductions in the expression of well-defined ATF6-target genes, including ER chaperone BiP (GRP78/HSPA5) and XBP1t and its spliced variant XBP1s (Figure 2A; Yoshida et al., 2001 blue right-pointing triangle; Baumeister et al., 2005 blue right-pointing triangle). ATF4 mRNA levels were also modestly reduced in the ATF6-depleted cells treated with tunicamycin, but there was no measurable reduction in ATF4 protein levels (Figure 2, A and B). Of importance, depletion of ATF6 sharply lowered the induction of CHOP mRNA and protein upon ER stress in the Hepa1-6 cells. The CHOP protein levels were reduced by 76 and 51% at 3 and 6 h, respectively. These results suggest that ATF6 can be a major contributor to CHOP expression, especially during ER stress. To address whether other ATF transcription factors regulated by PERK can effect CHOP expression, we depleted ATF5 expression in Hepa1-6 cells using shRNA and found no changes in induced expression of CHOP protein by ER stress (Figure 2C). These findings indicate that the requirement of ATF6 for induced CHOP expression in the Hepa1-6 hepatocytes is not broadly shared among other transcription factors controlled by PERK.
ATF6 - transcriptional factor (canonical)[ER stress - apotosis]
DDIT3 [ER stress - apoptosis - apoptosis inducer ]
CHOP - apotosis inducing factor (canonical)[ER stress - apotosis]
Apoptosis inducing gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature apoptosis inducing gene product or products (proteins or RNA). This entity is a specific course-dependent process. This process can constitute the course of ER stress.
apoptosis promoting gene expression [ER stress]
Apoptosis inducing gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature apoptosis inducing gene product or products (proteins or RNA).
ATF6 activation is a subtype of molecular activation: A process that changes the activity of the ATF6 (Activating Transcription Factor 6) to be higher. This process is dependent on ERAD and can constitute the course of ER stress.
Refolding gene expression by XBP1 is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) related to the protein refolding function by XBP1. This process is dependent on the refolding and can constitute the course of ER stress.
refolding gene expression by XBP1 [ER stress - refolding]
GRP170 - chaperone [ER stress - Refolding]
HYOU1 - chaperone (canonical)[ER stress - Refolding]
A comprehensive review of GRP170 as a putative GRP78 co-chaperone is available.
150-kDa oxygen-regulated protein (ORP150) suppresses hypoxia-induced apoptotic cell death.
A role played by the entity that assists chaperon and ensures correct protein folding.
XBP1 - transcriptional regulator (canonical)[ER stress - Refolding]
ATF6 activation is a subtype of molecular activation: A process that changes the activity of the ATF6 (Activating Transcription Factor 6) to be higher. This process is dependent on the inflammation and can constitute the course of ER stress.
ATF6 activation [ER stress - inflammation]
Positive regulation of gene expression via JNK signaling is a subtype of positive regulation of gene expression: A process that that activates or increases the frequency, rate or extent of gene expression via JNK signaling. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
positive regulation of gene expression via JNK signaling [ER stress]
Receiving abnormal protein signal by IRE1 is a subtype of receiving signal: A process that recognizes another object and changes into an abnormal protein (e.g., misfolded protein, etc.) signal by IRE1. This process is dependent on the apoptosis and can constitute the course of ER stress.
receiving abnormal protein signal by IRE1 [ER stress - apoptosis]
JNK - kinase (canonical)[ER stress - inflammation]
JNK - kinase (canonical)[ER stress - apotosis]
JNK - signalling factor (canonical)[ER stress - apotosis]
JNK - signalling factor (canonical)[ER stress - inflammation]
P-EIF2A - translation initiation inhibitor (canonical)[ER stress - translation]
EIF2A - translation initiation factor (canonical)[ER stress - translation]
A role played by the entity that activates, or increases the frequency, rate or extent of translation initiation
positive regulator role of translational initiation
GADD34 - phosphatase (canonical)[ER stress - translation]
IRE1-Traf2-ASK-JNK-Bcl2 pathway is a subtype of IRE1 signaling (integrated pathway): Sequence of linked reactions, which has IRE1-Traf2-ASK-JNK-BCL2 pathway and gene regulation. This pathway is dependent on the apoptosis and can constitute the course of ER stress.
IRE1-Traf2-ASK-JNK-Bcl2 pathway [ER stress - apoptosis]
TRAF2 activation by IRE1 is a subtype of molecular activation: A process that changes the activity of the TARF2 to be higher by IRE1. This process is dependent on the IRE1−TRAF2-ASK-JNK-Bcl2 pathway mediated apoptosis and can constitute the course of ER stress.
TRAF2 activation by IRE1 [ER stress - apoptosis - IRE1−TRAF2-ASK-JNK-Bcl2 pathway]
TRAF2 -IRE1 adaptor protein (canonical)[ER stress - apotosis -IRE1-JNK]
ASK activation is a subtype of molecular activation: A process that changes the activity of one of the ASK (apoptosis signal-regulating kinase) family to be higher. This process is dependent on the apoptosis and can constitute the course of ER stress.
ASK activation [ER stress - apoptosis - IRE1-TRAF2-ASK-JNK-Bcl2 pathway]
JNK activation is a subtype of molecular activation: A process that changes the activity of the JNK to be higher. This process is dependent on the IRE1−TRAF2-ASK-JNK-Bcl2 pathway mediated apoptosis and can constitute the course of ER stress.
JNK activation [ER stress - apoptosis - IRE1−TRAF2-ASK-JNK-Bcl2 pathway]
IRE1 - signaling factor (canonical)[ER stress - apotosis]
ASK - signaling factor (canonical)[ER stress - inflammation]
ASK - signaling factor (canonical)[ER stress - inflammation -TRAF2]
ASK - signaling factor (canonical)[ER stress - apotosis -TRAF2]
A process that changes the activity of the Bcl2 to be lower by JNK. This process is dependent on the IRE1-TRAF2-JNK pathway mediated apoptosis and can constitute the course of ER stress.
Inhibition of anti-apoptotic factor Bcl-2 results in the promotion of apoptosis.
Bcl2 inactivation by JNK [ER stress - apoptosis - IRE1-TRAF2-JNK pathway]
Bcl2 inactivation by JNK is a subtype of inactivating: A process that changes the activity of the Bcl2 to be lower by JNK.
BIM activation is a subtype of molecular activation: A process that changes the activity of the BIM (BCL2L11), BH3-only BCL-2 family, to be higher. This process is dependent on the IRE1−TRAF2-JNK-Bcl2 pathway mediated apoptosis and can constitute the course of ER stress.
BIM activation [ER stress - apoptosis - IRE1−TRAF2-JNK-Bcl2 pathway]
BIM activation is a subtype of molecular activation: A process that changes the activity of the BIM (BCL2L11), BH3-only BCL-2 family, to be higher.
Bcl2 phosphorylation by JNK is a subtype of Bcl2 phosphorylation: A process that The process of introducing a phosphate group into Bcl2 by JNK. This process is dependent on the apoptosis and can constitute the course of ER stress.
Bcl2 phosphorylation by JNK [ER stress - apoptosis]
Bcl2 phosphorylation by JNK is a subtype of Bcl2 phosphorylation: A process that The process of introducing a phosphate group into Bcl2 by JNK. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
IRE1 can bind to the adaptor protein TRAF2 to initiate the activation of ASK1 and JNK signaling pathways. JNK can then phosphorylate BCL-2 to reduce its antiapoptotic activity and phosphorylate the pro-apoptotic protein BIM (BCL2-interacting mediator of cell death) resulting in BCL-2-associated X protein (BAX)-dependent apoptosis.
Bcl2 phosphorylation by JNK is a subtype of Bcl2 phosphorylation: A process that The process of introducing a phosphate group into Bcl2 by JNK.
IRE1 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the IRE1 (Inositol-requiring transmembrane kinase/endonuclease). IRE1 generally plays a endoplasmic reticulum membrane stress sensor role. This process is dependent on the apoptosis and can constitute the course of ER stress.
IRE1 signaling (primitive) [ER stress - apoptosis]
A series of molecular signals mediated by the endoplasmic reticulum stress sensor IRE1 (Inositol-requiring transmembrane kinase/endonuclease). This process is dependent on the protein refolding that can constitute the course of ER stress.
Receiving abnormal protein signal by IRE1 is a subtype of receiving signal: A process that recognizes another object and changes into an abnormal protein (e.g., misfolded protein, etc.) signal by IRE1. This entity is a specific course-dependent process. This process can constitute the course of ER stress via protein refolding.
receiving abnormal protein signal by IRE1 [ER stress - refolding]
ATF6 - signaling factor (canonical)[ER stress -ERAD]
XBP1s gene regulation pathway is a subtype of gene regulation pathway: A series of process in which XBP1s regulates the gene expression. This process is dependent on the protein refolding and can constitute the course of ER stress.
XBP1s gene regulation pathway [ER stress - refolding]
XBP1s gene regulation pathway is a subtype of gene regulation pathway: A series of process in which XBP1s regulates the gene expression. This process is dependent on the inflammation that can constitute the course of ER stress.
XBP1s gene regulation pathway [ER stress - ERAD]
CHOP gene regulation pathway is a subtype of gene regulation pathway: Sequence of reactions to regulate genes by CHOP. This pathway is dependent on the apoptosis and can constitute the course of ER stress.
CHOP gene regulation pathway [ER stress - apoptosis]
NRF2 signaling (integrated pathway) is a subtype of integrated signaling pathway: Sequence of linked reactions, which has NRF2 signaling and gene regulation pathway. This pathway is a specific course-dependent process. This process can constitute the course of ER stress.
NRF2 gene regulation pathway [ER stress]
Refolding gene regulation pathway by ATF4 is a subtype of ATF4 gene regulation pathway: Sequence of reactions to regulate refolding genes by ATF4. This pathway can constitute the course of ER stress.
Refolding gene regulation pathway by ATF4 [ER stress]
Refolding gene expression by ATF4 is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) related to the refolding by ATF4. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
refolding gene expression by ATF4 [ER stress]
ATF4 - transcriptional regulator (canonical)[ER stress - Refolding]
Inflammatiory gene expression by ATF4 is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) related to apoptosis by ATF4. This process is dependent on the apoptosis and can constitute the course of ER stress.
apoptotic gene expression by ATF4 [ER stress - apoptosis]
Carbohydrate metabolism related gene expression by ATF4 is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) related carbohydrate metabolism by ATF4. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
carbohydrate metabolism gene expression by ATF4 [ER stress]
Lipid metabolism gene expression by ATF4 is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) related to the lipid metabolism by ATF4. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
lipid metabolism gene expression by ATF4 [ER stress]
ATF4 - transcriptional regulator (canonical)[ER stress - glucose metabolism disorder]
ATF4 - transcriptional regulator (canonical)[ER stress - dyslipidemia]
IRE1 dimerization is a subtype of protein dimerization: The formation of a IRE1 dimer, a macromolecular structure consists of two noncovalently associated identical or nonidentical subunits. This process is dependent on the refolding and can constitute the course of ER stress.
IRE1 dimerization [ER stress - refolding]
IRE1 dimer (canonical)[ER stress - Refolding]
IRE1 dimerization is a subtype of protein dimerization: The formation of a IRE1 dimer, a macromolecular structure consists of two noncovalently associated identical or nonidentical subunits. This entity is a specific course-dependent process. This process is dependent on ERAD and can constitute the course of ER stress.
IRE1 autophosphorylation is a subtype of protein autophosphorylation: The phosphorylation by IRE1 of one or more of its own amino acid residues (cis-autophosphorylation), or residues on IRE1 (trans-autophosphorylation). This process is dependent on the refolding and can constitute the course of ER stress.
IRE1 autophosphorylation [ER stress - refolding]
IRE1 autophosphorylation is a subtype of protein autophosphorylation: The phosphorylation by IRE1 of one or more of its own amino acid residues (cis-autophosphorylation), or residues on IRE1 (trans-autophosphorylation). This process is dependent on the ERAD and can constitute the course of ER stress.
IRE1 autophosphorylation [ER stress - ERAD]
IRE1 - autophosphorylation kinase (canonical)[ER stress - Refolding]
IRE1 - autophosphorylation kinase (canonical)[ER stress -ERAD]
Translocation of XBP1s from the cytosol to the nucleus is a subtype of nuclear transport: A process that of the directed movement of XBP1s from the cytoplasm to the nucleus.
Translocation of XBP1s from the cytosol to the nucleus
Translocation of XBP1s from the cytosol to the nucleus is a subtype of nuclear transport: A process that of the directed movement of XBP1s from the cytoplasm to the nucleus. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Translocation of XBP1s from the cytosol to the nucleus [ER stress]
Translocation of XBP1s from the cytosol to the nucleus is a subtype of nuclear transport: A process that of the directed movement of XBP1s from the cytoplasm to the nucleus. This process is dependent on the refolding and can constitute the course of ER stress.
Translocation of XBP1s from the cytosol to the nucleus [ER stress - refolding]
Translocation of XBP1s from the cytosol to the nucleus is a subtype of nuclear transport: A process that of the directed movement of XBP1s from the cytoplasm to the nucleus. This entity is a specific course-dependent process. This process is dependent on the ERAD and can constitute the course of ER stress.
Translocation of XBP1s from the cytosol to the nucleus [ER stress - ERAD]
XBP1s gene regulation pathway is a subtype of gene regulation pathway: A series of process in which XBP1s regulates the gene expression. This pathway is dependent on the inflammation and can constitute the course of ER stress.
XBP1s gene regulation pathway[ER stress - inflammation]
Translocation of XBP1s from the cytosol to the nucleus is a subtype of nuclear transport: A process that of the directed movement of XBP1s from the cytoplasm to the nucleus. This process is dependent on the inflammation and can constitute the course of ER stress.
Translocation of XBP1s from the cytosol to the nucleus [ER stress - inflammation]
PERK-eIF2a-CyclinD1 pathway is a subtype of PERK-eIF2a signaling: Sequence of linked reactions, which has PERK-eIF2a signaling and CyclinD1 gene regulation. This pathway is dependent on the cell cycle arrest and can constitute the course of ER stress.
PERK-eIF2a-CyclinD1 pathway [ER stress - cell cycle arrest]
Regulation of cell cycle related gene expression is a subtype of regulation of gene expression: A process that modulates the frequency, rate or extent of cel cycle related gene expression. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
regulation of cell cycle related gene expression [ER stress]
Negative regulation of formation of cytoplasmic translation initiation complex is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of formation of cytoplasmic translation initiation complex. This process is dependent on the inflammation and can constitute the course of ER stress.
negative regulation of formation of cytoplasmic translation initiation complex by eIF2a [ER stress - inflammation]
Any process that stops, prevents, or reduces the frequency, rate or extent of Cyclin D1 translation by eIF2a. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
attenuation of Cyclin D1 translation by eIF2a [ER stress]
Negative regulation of cell cycle regulator gene expression is a subtype of negative regulation of gene expression: A process that stops, prevents, or reduces the frequency, rate or extent of cell cycle regulator gene expression. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
negative regulation of cell cycle regulator gene expression [ER stress]
A process in which a signal to eIF2a is transduced by PERK. This process is dependent on the cell cycle arrest and can constitute the course of ER stress.
PERK signaling to eIF2a [ER stress - cell cycle arrest]
Receiving abnormal protein signal by PERK is a subtype of receiving signal: A process that recognizes another object and changes into an abnormal protein (e.g., misfolded protein, etc.) signal by PERK. This entity is a specific course-dependent process. This process can constitute the course of ER stress via cell cycle arrest.
receiving abnormal protein signal by PERK [ER stress - cell cycle arrest]
PERK - signal sensor (canonical)[ER stress - cell cycle arrest]
PERK - signal sensor (canonical)[ER stress - Refolding]
Dissociation of PERK:BIP heterodimer is a subtype of detaching: A process that disaggregates PERK-BIP heterodimers into BIP and PERK. This process is dependent on the cell cycle arrest and can constitute the course of ER stress.
Dissociation of PERK:BIP Heterodimer [ER stress - cell cycle arrest]
PERK - stress sensor (canonical)[ER stress - cell cycle arrest]
PERK autophosphorylation is a subtype of protein autophosphorylation: The phosphorylation by PERK of one or more of its own amino acid residues (cis-autophosphorylation), or residues on PERK (trans-autophosphorylation). This process is dependent on the cell cycle arrest and can constitute the course of ER stress.
PERK autophosphorylation [ER stress - cell cycle arrest]
PERK - autophosphorylation kinase (canonical)[ER stress - cell cycle arrest]
PERK - kinase (canonical)[ER stress - cell cycle arrest]
Phosphorylation of eIF2-alpha by PERK is a subtype of eIF2a phosphorylation: A process that The process of introducing a phosphate group into eIF2a by PERK. This process is dependent on the cell cycle arrest and can constitute the course of ER stress.
Phosphorylation of eIF2-alpha by PERK [ER stress - cell cycle arrest]
A process that changes the activity of the eIF2a by PERK. This process is dependent on the cell cycle arrest and can constitute the course of ER stress.
changing activity of eIF2a by PERK [ER stress - cell cycle arrest]
PERK activation is a subtype of Molecular activation: A process that changes the activity of PERK to be higher. This process is dependent on the cell cycle arrest and can constitute the course of ER stress.
PERK activation [ER stress - cell cycle arrest]
PERK - signaling factor (canonical)[ER stress - cell cycle arrest]
PERK dimerization is a subtype of protein dimerization: The formation of a PERK dimer, a macromolecular structure consists of two noncovalently associated identical or nonidentical subunits. This entity is a specific course-dependent process. This process is dependent on the process of cell cycle arrest and can constitute the course of ER stress.
PERK dimerization [ER stress - cell cycle arrest]
PERK dimer (canonical)[ER stress - cell cycle arrest]
Activated PERK can phosphorylate eIF2α. Phospho-eIF2α leads to translation attenuation with immediate effects on proteins with short half-lives Cyclin D1 which results in immediate cell cycle arrest.
Changing calcium ion concentration is a subtype of changing concentration: A process that changes the calcium ion concentration in the blood.
Changing calcium ion concentration in ER is a subtype of changing calcium ion concentration: A process that changes the calcium ion concentration in the endoplasmic reticulum (ER). This entity is a specific course-dependent process. This process can constitute the course of ER stress.
changing calcium ion concentration in ER [ER stress]
Ritonavir and lopinavir may also have effects on ER Ca2+ levels by inhibition of SERCA
Changing calcium ion concentration in ER is a subtype of changing calcium ion concentration: A process that changes the calcium ion concentration in the endoplasmic reticulum (ER).
changing calcium ion concentration in ER
HIV protease inhibitor lopinavir-induced TNF-alpha and IL-6 expression is coupled to the unfolded protein response and ERK signaling pathways in macrophages.
HIV protease inhibitors induce endoplasmic reticulum stress and disrupt barrier integrity in intestinal epithelial cells.
ER stress dependent chemical compound is a subtype of toxic course dependent chemical entity. This entity (drug) can participate in the course of ER stress.
Negative regulation of SERCA gene expression is a subtype of negative regulation of gene expression: A process that stops, prevents, or reduces the frequency, rate or extent of SERCA gene expression.
negative regulation of SERCA gene expression
Negative regulation of SERCA gene expression is a subtype of negative regulation of gene expression: A process that stops, prevents, or reduces the frequency, rate or extent of SERCA gene expression. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
negative regulation of SERCA gene expression [ER stress]
In alcohol plus RIT and LOP, alcohol synergistically increased the HIV drug-induced GRP78 and ratio of spliced sXbp1 to Xbp1. In addition, RIT and LOP inhibited protein expression of the Sarco/ER Calcium-ATPase (SERCA) which was further inhibited in the presence of alcohol. CYP2E1 was not significantly affected in response to any of these acute treatments. An increased alcohol exposure induces oxidative stress and/or hyperhomocysteinmia, which disturb SERCA further and exacerbate the HIV drug-induced ER stress leading to hepatic steatosis and fibrosis
Reduced endoplasmic reticulum luminal calcium links saturated fatty acid-mediated endoplasmic reticulum stress and cell death in liver cells.
Negative regulation of endoplasmic reticulum-associated degradation is a subtype of negative regulation of protein catabolic process: A process that stops, prevents, or reduces the frequency, rate or extent of endoplasmic reticulum-associated degradation. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
negative regulation of endoplasmic reticulum-associated degradation [ER stress]
Any process that stops, prevents or reduces the frequency, rate or extent of proteasomal protein catabolic process. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
negative regulation of proteasomal protein catabolic process [ER stress]
Hepatic CYP3A suppression by high concentrations of proteasomal inhibitors (MG-132): a consequence of endoplasmic reticulum (ER) stress induction, activation of PERK and general control nonderepressible-2 eIF2alpha kinase (GCN2), and global translational shutoff.
ATP Binding Cassette Subfamily C Member 5
ATP-Binding Cassette, Sub-Family C (CFTR/MRP), Member 5
Multi-Specific Organic Anion Transporter C
Multidrug Resistance-Associated Protein 5
ATP Binding Cassette Subfamily C Member 4
ATP-Binding Cassette, Sub-Family C (CFTR/MRP), Member 4
Multidrug Resistance-Associated Protein 4
Marked (approximately 4-fold) MG132 concentration-dependent PERK autophosphorylation, along with an 8-fold increase in eIF2alpha-phosphorylation was found. MG132 also activated GCN2 [general control nonderepressible-2 (EIF2AK4)] eIF2alpha kinase in a concentration-dependent manner, but not the heme-regulated inhibitor eIF2alpha kinase [(EIF2AK1)]. Pulse-chase, immunoprecipitation/immunoblotting analyses documented the consequently dramatic translational shutoff of total hepatic protein, including but not limited to CYP3A and tryptophan 2,3-dioxygenase protein syntheses. These findings reveal that at high concentrations, MG132 is indeed cytotoxic and can suppress CYP3A synthesis, a result confirmed by confocal immunofluorescence analyses of MG132-treated hepatocytes
Intercellular transmission of the unfolded protein response promotes survival and drug resistance in cancer cells.
Peroxisome Proliferator-Activated Receptor Alpha - inactivated[lipidosis]
PPARA - inactivated (canonical)[lipidosis]
HIV-1 protease inhibitors nelfinavir and atazanavir induce malignant glioma death by triggering endoplasmic reticulum stress.
New therapeutic strategy for hepatocellular carcinoma by molecular targeting agents via inhibition of cellular stress defense mechanisms.
RACK1 modulates apoptosis induced by sorafenib in HCC cells by interfering with the IRE1/XBP1 axis.
Alpha-fetoprotein is a biomarker of unfolded protein response and altered proteostasis in hepatocellular carcinoma cells exposed to sorafenib. Sorafenib activated the Regulated Inositol-Requiring Enzyme-1α (IRE-1α) and the PKR-like ER Kinase (PERK)-dependent arms of the Unfolded Protein Response (UPR). The inhibition of IRE-1α partially restored the mRNA levels of AFP upon treatment with sorafenib. The inhibition of both pathways partially prevented the drop in the production of AFP induced by sorafenib.
Intrinsic apoptosis signaling (primitive) is a subtype of signaling [biological]: A process in which an intracellular signal is conveyed to trigger the apoptotic death of a cell. The process starts with reception of an intracellular signal (e.g. DNA damage, endoplasmic reticulum stress, oxidative stress etc.). This process is crucially regulated by permeabilization of the mitochondrial outer membrane (MOMP). This entity is a specific course-dependent process. This process can constitute the course of Cell death.
intrinsic apotosis signaling (primitive)
Quercetin ameliorates HFD-induced NAFLD by promoting hepatic VLDL assembly and lipophagy via the IRE1a/XBP1s pathway.
Hepatic MCP1, CTGF, P4HA1, Col1α1, and Mmp9, target genes of miR-122, were upregulated in CCl4-treated mice. Interestingly, STF-083010 reversed CCl4-induced hepatic miR-122 downregulation. STF-083010 inhibited CCl4-induced upregulation of miR-122 target genes. Therefore, STF-083010 alleviated CCl4-induced liver injury and thus protected against liver fibrosis associated with hepatic miR-122.
Receiving abnormal protein signal by ATF6 is a subtype of receiving signal: A process that recognizes another object and changes into an abnormal protein (e.g., misfolded protein, etc.) signal by ATF6. This process is dependent on the apoptosis and can constitute the course of ER stress.
receiving abnormal protein signal by ATF6 [ER stress - apoptosis]
Dissociation of ATF6:BIP heterodimer is a subtype of detaching: A process that disaggregates ATF6-BIP heterodimers into BIP and ATF6. This process is dependent on the apoptosis and can constitute the course of ER stress.
Dissociation of ATF6-alpha:BIP Complex [ER stress - apoptosis]
ATF6 - stress sensor (canonical)[ER stress - apotosis]
Proapoptic gene regulation pathway by ATF6 is a subtype of ATF6 gene regulation pathway: Sequence of reactions to regulate genes which have a proapoptosis inducer role by ATF6. This process can constitute the course of ER stress.
proapoptic gene regulation pathway by ATF6 [ER stress]
HSP90B1 - chaperone (canonical)[ER stress -Refolding [persist]]
ATF4 gene expression by eIF2a is a subtype of gene expression: The process in which a gene sequence is converted into a mature ATF4 gene product or products (proteins or RNA) by eIF2a. This process is dependent on the inflammation and can constitute the course of ER stress.
ATF4 gene expression by eIF2a [ER stress - inflammation]
Inflammatiory gene expression by ATF4 is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) related to the induction of inflammation by ATF4. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
inflammatory gene expression by ATF4 [ER stress]
Expression of NLRP1, a core inflammasome component, is specifically up-regulated during severe ER stress conditions in human cell lines. Both IRE1α and PERK, but not the ATF6 pathway, modulate NLRP1 gene expression. ATF4 transcription factor directly binds to NLRP1 promoter during ER stress.
The PERK pathway has been shown to induce inflammation through the direct binding of ATF4 to the Il6 promoter
ATF4 increases expression of inflammatory cytokines, including IL-6and monocyte chemoattractant protein-1 (MCP-1), by inducing transcription of the NACHT, LRR, and PYD domain-containing protein 1 (NLRP1), a core component of the inflammasome. I
IL-6 - inflammatory cytokine (canonical)[ER stress - inflammation -ATF4 pathway]
Chronic inflammation is a molecular element of the metabolic syndrome and type 2 diabetes. Saturated fatty acids (SFAs) are considered to be an important proinflammatory factor. ATF 4, a transcription factor that is induced downstream of metabolic stresses including endoplasmic reticulum (ER) stress, plays critical roles in SFA-induced interleukin-6 (Il6) expression. ATF4 exerts its proinflammatory effects through at least two different mechanisms: ATF4 is involved in SFA-induced nuclear factor-κB activation; and ATF4 directly activates the Il6 promoter.
NLRP1 - inflammatory substance (canonical)[ER stress]
A role played by the entity that has inflammatory effects.
The totality of all processes through which a typeII instance is realized.
Inflammatory cytokine gene expression via ATF4 is a subtype of gene expression: The process in which a gene sequence is converted into a mature inflammatory cytokine gene product or products (proteins or RNA) via ATF4. This process is dependent on the inflammation and can constitute the course of ER stress.
inflammatory cytokine gene expression via ATF4 [ER stress - inflammation]
ATF6-CREBPH-APR pathway is a subtype of ATF6 signaling (integrated pathway): Sequence of linked reactions, which has ATF6 signaling and gene regulation pathway. This process is dependent on positive inflammation and can constitute the course of ER stress.
ATF6-CREBPH-APR pathway [ER stress - inflammation]
APR gene expression by ATF6. is a subtype of Gene expression by transcriptional regulator: The process in which the sequence of APR is converted into a mature gene product or products (proteins or RNA) by ATF6. This process is dependent on the ATF6-ARP mediated inflammation and can constitute the course of ER stress.
APR gene expression by ATF6 [ER stress - inflammation - ATF6-ARP]
In this study,(1) expression of CREBH is liver specific and is induced by proinflammatory cytokines; (2) ER stress induces cleavage of CREBH to release an N-terminal fragment that traffics to the nucleus to activate transcription; (3) CREBH activation requires processing by Golgi-localized proteases S1P and S2P; (4) CREBH does not contribute to the classical UPR induction but is required for the APR by regulating transcription of the CRP and SAP genes; (5) CREBH and ATF6 bind to a conserved promoter element in the specific APR genes; (6) CREBH and ATF6 interact and synergistically activate transcription of target genes in hepatocytes upon ER stress; and (7) proinflammatory cytokines induce cleavage of CREBH and activate the APR and the UPR in the liver in vivo.
ATF6 - transcriptional factor (canonical)[ER stress - inflammation]
ATF6 -APR transcriptional factor (canonical)[ER stress - inflammation -APR]
Acute Phase Response molecule [ER stress]
CREBH and ATF6 activate transcription from the SAP (E) and CRP promoters.
ER stress in hepatocytes, ATF6α and CREBH traffic to the Golgi to undergo S1P- and S2P–mediated cleavage; the cytosolic active transcription factors that are released induce the expression of APR genes, including those encoding C-reactive protein and serum amyloid P component
GRP94 - chaperone (canonical)[proteinrefolding [persist]]
XBP1 - transcriptional regulator (canonical)[ER stress - Refolding -ATF6 pathway]
Refolding promotor is a role played by any substance that promotes the process of refolding.
DNAJC3 -cochaperone (canonical)[ER stress -Refolding [persist]]
ATF4 gene expression by eIF2a is a subtype of gene expression: The process in which a gene sequence is converted into a mature ATF4 gene product or products (proteins or RNA) by eIF2a. This process is dependent on the retranslation process and can constitute the course of ER stress.
ATF4 gene expression by eIF2a [ER stress - translation]
ATF4 - transcriptional regulator (canonical)[ER stress - translation]
Tranlation promotion gene expression by ATF4 is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) related to the translation promotion by ATF4. This process is dependent on the retranslation process and can constitute the course of ER stress.
tranlation promotion gene expression by ATF4 [ER stress]
Perk->eIF2a-> translation attenuation Perk -> eIF2a->ATF4->GADD34 expression->eIF2a inactivation (dephosphorylation) by GADD34-> restoring translation GAA34 is a regulatory subunit of protein posphatase 1 (PP1).
GADD34 gene expression by ATF4 is a subtype of gene expression by transcriptional factor: The process in which a gene sequence of GADD34 is converted into a mature gene product or products (proteins or RNA) by ATF4. This process is dependent on the retranslation process and can constitute the course of ER stress.
GADD34 gene expression by ATF4 [ER stress]
PERK-eIF2a-ATF4 mediated pathway is a subtype of PERK-eIF2a signaling: Sequence of linked reactions, which has PERK-eIF2a signaling and GADD34 gene regulation by ATF4. This pathway is dependent on the retranslation and can constitute the course of ER stress.
PERK-ATF4-GADD34 signaling [ER stress - retranslation]
A process in which a signal to eIF2a is transduced by PERK. This process is dependent on the translation and can constitute the course of ER stress.
PERK signaling to eIF2a [ER stress - translation]
Peroxisome fatty acid beta oxidation gene expression is a subtype of gene expression: A process that The process in which a gene sequence is converted into a mature peroxisome fatty acid beta oxidation gene product or products (proteins or RNA) persistently. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
peroxisome fatty acid beta oxidation gene expression(sustained) [Eosinophilic granular degeneration]
A series of molecular signals in which a signal is conveyed from the cell surface to trigger the apoptotic death of a cell. The pathway starts with a ligand binding to a death domain receptor on the cell surface, and ends when the execution phase of apoptosis is triggered. This pathway is a specific course-dependent and can constitute the course of cell death.
extrinsic apoptotic signaling pathway via death domain receptors [cell death]
ATF6 processing is a subtype of protein processing: A process that ATF6 maturation process achieved by the cleavage of a peptide bond or bonds within ATF6 protein.
IRE1 autophosphorylation is a subtype of protein autophosphorylation: The phosphorylation by IRE1 of one or more of its own amino acid residues (cis-autophosphorylation), or residues on IRE1 (trans-autophosphorylation). This entity is a specific course-dependent process. This process is dependent on RODD and can constitute the course of ER stress.
IRE1 autophosphorylation [ER stress - RIDD]
Inflammatory gene expression by XBP1 is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) related to the inflammation by XBP1. This process is dependent on the inflammation and can constitute the course of ER stress.
inflammatory gene expression by XBP1 [ER stress - inflammation]
XBP1 - transcriptional regulator (canonical)[ER stress - inflammation]
IL-6 - inflammatory cytokine (canonical)[ER stress - inflammation -XBP1 pathway]
ARP related gene expression via ATF6 is a subtype of gene expression: The process in which a gene sequence is converted into a mature ARP gene product or products (proteins or RNA) ia ATF6. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
ARP related gene expression via ATF6 [ER stress]
C-reactive protein - inflammatory substance [ER stress]
CRP - inflammatory substance (canonical)[ER stress]
ARP related gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature ARP gene product or products (proteins or RNA) by PERK.
ATF6 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the ATF6 (activating transcription factor 6). ATF6 generally plays a endoplasmic reticulum membrane stress sensor role. This process is dependent on the ATF6-ARP mediated inflammation and can constitute the course of ER stress.
ATF6 signaling (primitive) [ER stress - inflammation - ATF6-ARP]
ATF6 activation is a subtype of molecular activation: A process that changes the activity of the ATF6 (Activating Transcription Factor 6) to be higher. This process is dependent on the ARP mediated inflammation and can constitute the course of ER stress.
ATF6 activation [ER stress - inflammation - ARP]
ATF6 processing is a subtype of protein processing: A process that ATF6 maturation process achieved by the cleavage of a peptide bond or bonds within ATF6 protein. This process is dependent on the inflammation and can constitute the course of ER stress.
ATF6 processing [ER stress - inflammation]
Cleavage of CREB by S1P is a subtype of proteolysis: A process in which CREB is cleaved by endopeptidase S1P( MBTPS1). This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Cleavage of CREB by S1P is a subtype of proteolysis: A process in which CREB is cleaved by endopeptidase S1P( MBTPS1).
Cleavage of CREB by S2P is a subtype of proteolysis: A process in which CREB is cleaved by endopeptidase S2P( MBTPS2). Site-2 cleavage comes after site-1 cleavage
Cleavage of CREB by S2P is a subtype of proteolysis: A process in which CREB is cleaved by endopeptidase S2P( MBTPS2). Site-2 cleavage comes after site-1 cleavage This entity is a specific course-dependent process. This process can constitute the course of ER stress.
CERB processing is a subtype of protein processing: CREB maturation process achieved by the cleavage of a peptide bond or bonds within CREB protein. This process is dependent on the ARP mediated inflammation and can constitute the course of ER stress.
CERB processing [ER stress - inflammation -ARP]
CREB3L3 activation is a subtype of molecular activation: A process that changes the activity of the CREBL3 to be higher. This process is dependent on the rinflammation and can constitute the course of ER stress.
CREB3L3 activation [ER stress - inflammation - ARP]
CREB3L3 signaling is a subtype of signaling [biological]: A process that in which a signal transmitted by CREB3L3. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
CREB3L3 signaling [ER stress - inflammation]
CREBPH - signaling factor (canonical)[ER stress - inflammation]
ARP gene regulation pathway by ATF6 is a subtype of ATF6 gene regulation pathway: Sequence of reactions to regulate acute response protein (ARP) genes by ATF6. This process can constitute the course of ER stress.
ARP gene regulation pathway by ATF6 [ER stress]
CREBPH -APR transcriptional factor (canonical)[ER stress - inflammation -APR]
serum amyloid P-component - inflammatory factor [ER stress]
SAP - inflammatory factor (canonical)[ER stress]
IRE1 - autophosphorylation kinase (canonical)[ER stress -RIDD]
IRE1 dimerization is a subtype of protein dimerization: The formation of a IRE1 dimer, a macromolecular structure consists of two noncovalently associated identical or nonidentical subunits. This entity is a specific course-dependent process. This process is dependent on RIDD and can constitute the course of ER stress.
Caspase 12 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the caspase 12. This process is dependent on the apoptosis and can constitute the course of ER stress.
caspase 12 signaling (primitive) [ER stress - apoptosis]
Caspase 4 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the caspase 4. This process is dependent on the apoptosis and can constitute the course of ER stress.
ミトコンドリア(intrinsic)と独立のパスウェイ
caspase 4 signaling (primitive) [ER stress - apoptosis]
Caspase-12 activation is a subtype of caspase activation: A process that changes the activity of the caspase-12, intracellular cysteine endopeptidase family members, to be higher. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Caspase-4 activation is a subtype of caspase activation: A process that changes the activity of the caspase-4, intracellular cysteine endopeptidase family members, to be higher. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Caspase activation is a subtype of molecular activation: A process that changes the activity of the caspase, intracellular cysteine endopeptidase family members, to be higher.
Caspase-9 activation is a subtype of caspase activation: A process that changes the activity of the caspase-9, intracellular cysteine endopeptidase family members, to be higher. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Caspase-3 activation is a subtype of caspase activation: A process that changes the activity of the caspase-3, intracellular cysteine endopeptidase family members, to be higher. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Expression of catalytic inactive PCK1(C288S) mutant reduced, but not completely inhibited the cleavage of caspase-3.
Caspase-3 activation is a subtype of caspase activation: A process that changes the activity of the caspase-3, intracellular cysteine endopeptidase family members, to be higher.
Caspase-9 activation is a subtype of caspase activation: A process that changes the activity of the caspase-9, intracellular cysteine endopeptidase family members, to be higher.
Caspase-12 activation is a subtype of caspase activation: A process that changes the activity of the caspase-12, intracellular cysteine endopeptidase family members, to be higher.
Caspase-4 activation is a subtype of caspase activation: A process that changes the activity of the caspase-4, intracellular cysteine endopeptidase family members, to be higher.
A series of molecular signals mediated by Caspase family. This pathway is a specific course-dependent and can constitute the course of ER stress. This pathway is dependent on the apoptosis and can constitute the course of ER stress.
Caspase 9 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the caspase 9. This process is dependent on the apoptosis and can constitute the course of ER stress.
caspase 9 signaling (primitive) [ER stress - apoptosis]
Caspase 3 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the caspase 3. This process is dependent on the apoptosis and can constitute the course of ER stress.
caspase 3 signaling (primitive) [ER stress - apoptosis]
The process that results in the movement of cytochrome c from the mitochondrial intermembrane space into the cytosol, which is part of the apoptotic signaling pathway and leads to caspase activation. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Permeabilization of the outer mitochondrial membrane by pro-apoptotic BCL2 family proteins, such as BAK and BAX, allows cytochrome c eflux from the mitochondrial intermembrane space into the cytosol (Arnoult et al. 2003).
release of cytochrome c from mitochondria [ER stress]
BAK activation is a subtype of molecular activation: A process that changes the activity of the BAK1 (BCL2 Antagonist/Killer 1), BCL-2 family, to be higher.
BAK activation is a subtype of molecular activation: A process that changes the activity of the BAK1 (BCL2 Antagonist/Killer 1), BCL-2 family, to be higher. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
BAX activation is a subtype of molecular activation: A process that changes the activity of the BAX (BCL2 Associated X, Apoptosis Regulator), BCL-2 family, to be higher.
BAX activation is a subtype of molecular activation: A process that changes the activity of the BAX (BCL2 Associated X, Apoptosis Regulator), BCL-2 family, to be higher. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
The aggregation, arrangement and bonding together of the apoptosome, a multisubunit protein complex involved in the signaling phase of the apoptotic process. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
A series of molecular signals in which an intracellular signal is conveyed to trigger the apoptotic death of a cell. The pathway starts with reception of an intracellular signal (e.g. DNA damage, endoplasmic reticulum stress, oxidative stress etc.), and ends when the execution phase of apoptosis is triggered. The intrinsic apoptotic signaling pathway is crucially regulated by permeabilization of the mitochondrial outer membrane (MOMP). This pathway is a specific course-dependent and can constitute the course of cell death.
intrinsic apoptotic signaling pathway [cell death]
Bax/Bak complex formation is a subtype of protein complex assembly: A process that forms a complex consisting of BAX/BAK, a member of the Bcl-2 family. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
BAX and BAK homo-oligomerize at the ER membrane, leading to its permeabilization and the release of ER luminal proteins to the cytosol.
BAX/BAK formed a protein complex with the cytosolic domain of IRE1alpha that was essential for IRE1alpha activation. Thus, BAX and BAK function at the ER membrane to activate IRE1alpha signaling and to provide a physical link between members of the core apoptotic pathway and the UPR.
Mitochondrial cytochrome c release can also be mediated by BAK and BAX which oligomerize and form a pore in the outer mitochondrial membrane, given the appropriate pro-apoptotic signals. BAX and BAK can also insert into the ER membrane to mediate Ca2+ release into the cytosol activating calpains.
Bax-Bak complex formation is a subtype of protein complex assembly: A process that forms a complex consisting of BAX/BAK, a member of the Bcl-2 family.
Changes in Bsep localization are involved in E217G-induced impairment of bile flow and bile salt transport.a Mrp2 is required for E217G to induce its harmful effect.
estradiol-17beta-glucuronide inhibited ATP-dependent taurocholate transport only in normal canalicular plasma membrane and in Bsep/Mrp2-coexpressing Sf9 cell vesicles, but not in Mrp2-deficient, indicating trans-inhibitionof Bsep only after its secretion into bile canaliculi by Mrp2.
esgtradiol‐17β‐ glucuronide [Cholestasis]
Positive regulation of gene expression via JNK signaling is a subtype of positive regulation of gene expression: A process that that activates or increases the frequency, rate or extent of gene expression via JNK signaling.
positive regulation of gene expression via JNK signaling
Binding to bile canaliculus membrane transporter by drug is a subtype of protein binding: Interacting process with the membrane transporter of bile canaliculus by the drug.
binding to bile canaliculus membrane transporter by drug
Sulindac is secreted into bile in unconjugated form by a canalicular bile acid transporter and is absorbed by cholangiocytes, inducing hypercholeresis. At high flux rates, sulindac competitively inhibits canalicular bile salt transport and may induce cholestasis in patients.
Back-flow is a subtype of changing direction: A process that changes the flow to the opposite direction.
BAK activation is a subtype of molecular activation: A process that changes the activity of the BAK1 (BCL2 Antagonist/Killer 1), BCL-2 family, to be higher. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
Import substances into hepatocyte vascular side (sinusoidal side) membrane is a subtype of transport: A process of the directed movement of substances into hepatocyte vascular side (sinusoidal side) membrane.
import substances into hepatocyte vascular side (sinusoidal side) membrane
CYP7A Promoter-Binding Factor [Cholestasis]
Negative regularuion of bile acid and bile salt transport is a subtype of negative regulation of transport: Any process that stops, prevents, or reduces the frequency, rate or extent of a bile acid and bile salts transport .
negative regularuion of bile acid and bile salt transport
This gene encodes a sodium-independent transporter which mediates cellular uptake of organic ions in the liver. Its substrates include bile acids, bromosulphophthalein, and some steroidal compounds. The protein is a member of the SLC21A family of solute carriers. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2008]
Solute Carrier Organic Anion Transporter Family Member 1A2 [Cholestasis]
Contraction is a subtype of generating motion: A process that generates the directed movement in which the object decreases in volume.
Bile accumulation is a subtype of accumulation of substances in a biological object: A process that keeps bile within the liver (intrahepatic), or outside the liver (extrahepatic) in the bile duct system.
Erythromycin estolate, troglitazone, and bosentan resulted in a decrease in , bile excretion and in vitro biliary clearance of euterium-labeled sodium taurocholate
Cyclosporine, an MDR1 substrate, can cause cholestatic liver injury through a number of different mechanisms: i) Competitive inhibition of ATP dependent transporters, ii) Iinhibition of intrahepatic vesicle transport and targeting of ATP dependent transporters to the canalicular membrane and iii) Impairment of bile secretion partly by increasing canalicular membrane fluidity without affecting the expression of canalicular transporter.
cyclosporine reduces the expression of glutathione synthesizing enzymes and the canalicular glutathione efflux system, MRP2, leading to reduced bile salt-independent bile flow
A cellular transport process in which transported substances are moved in membrane-bounded vesicles; transported substances are enclosed in the vesicle lumen or located in the vesicle membrane. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
vesicle-mediated transport [Cholestasis]
Increasing glutathione is a subtype of increasing quantity: A process that changes the amount of glutathione to be higher. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
Cholesterol biosynthetic process is a subtype of lipid biosynthetic process: The chemical reaction resulting in the formation of cholesterol, cholest-5-en-3 beta-ol, the principal sterol of vertebrates and the precursor of many steroids, including bile acids and steroid hormones. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
cholesterol biosynthetic process [Cholestasis]
Increasing bile level is a subtype of increasing quantity: A process that changes the amount of bile to be higher. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
Increasing materials for bile formation is a subtype of increasing quantity: A process that changes the amount of bile formation material to be higher. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
increasing materials for bile formation [Cholestasis]
Regulation of transporter gene expression by cytokine is a subtype of regulation of transporter gene expression: A process that changes the the gene expression level of the transporter by cytokines.
IL-1beta, TNF-alpha or IL-6 alters human hepatic transporters expression. Bile salt transporters as well as sinusoidal solute carrier transporters are usually repressed, whereas ATP-binding cassette drug efflux pumps remain unchanged or are either downregulated or upregulated. They maight alter drug pharmacokinetics, impairment of bile salt secretion and cholestasis caused by inflammation in humans.
regulation of transporter gene expression by cytokine
Regulation of transporter gene expression is a subtype of regulation of gene expression: A process that changes the the gene expression level of the transporter.
regulation of transporter gene expression
Decreasing bile acid production level is a subtype of decreasing quantity: A process that changes the production amount of bile acid to be lower.
Bile thrombus formation is a subtype of biological structure formation: A process that construcyss bile thrombus.
Bile thrombus formation in bile canaliculus is a subtype of bile thrombus formation: A process that constructs bile thrombus in bile canaliculus.
bile thrombus formation in bile canaliculus
Farnesoid X receptor activation is a subtype of activating nuclear receptor: A process that changes the activity of the activating FxR (farnesoid X receptor) with a nuclear receptor role to be higher.
Increasing materials for bile formation is a subtype of increasing quantity: A process that changes the amount of bile formation material to be higher.
Farnesoid X Receptor Pathway is a subtype of gene regulation pathway: Sequence of reactions to regulate genes by nuclear receptor Farnesoid X Receptor.
Gene expression by farnesoid X receptor is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) by Farnesoid X receptor (FXR).
Gene expression by farnesoid X receptor is a subtype of gene expression by transcriptional factor: The process in which a gene sequence is converted into a mature gene product or products (proteins or RNA) by Farnesoid X receptor (FXR). This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
bile acid transport gene expression by FXR [cholestasis]
gene expression by farnesoid X receptor [Cholestasis]
Farnesoid X Receptor Pathway is a subtype of gene regulation pathway: Sequence of reactions to regulate genes by nuclear receptor Farnesoid X Receptor. This entity is a specific course-dependent process. This process can constitute the course of cholestasis.
Farnesoid X receptor (FXR, a.k.a. NR1H4) is a nuclear receptor that responds to levels of bile acids present in the body and regulates many processes related to bile acids synthesis and transport.
Farnesoid X Receptor Pathway [cholestasis]
Acumulation of bile pigment in hepatocyte is a subtype of bile pigment deposition: The aggregation of bile pigmentin a particular location in a hepatocyte.
acumulation of bile pigment in hepatocyte
Increasing glutathione is a subtype of increasing quantity: A process that changes the amount of glutathione to be higher.
Excretion of drug metabolite from hepatocyte to bile tube is a subtype of compound excretion: A process that excretes the drug metabolite from the hepatocyte to to the bile tube.
excretion of drug metabolite from hepatocyte to bile tube
Drug export from the hepatocyte to to bile tube is a subtype of compound excretion: A process that excretes the drug from the hepatocyte to the bile tube.
drug export from the hepatocyte to to bile tube
Regulation of transporter gene expression by cytokine is a subtype of regulation of transporter gene expression: A process that changes the the gene expression level of the transporter by cytokines. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
regulation of transporter gene expression by cytokine [Cholestasis]
Negative regulation of contractile movement of bile canaliculus is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of contractile movement of bile canaliculus.
negative regulation of contractile movement of bile canaliculus
A role played by a process that consitutes the toxic course.
Bip-unfolded protein is a subtype of a molecular complex. This entity has sub-parts of molecules: BIP/GRP78, and an unfolded protein. This entity is dependent on ER stress.
Bip-unfolded protein complex [ER stress]
A role played by the entity which regulates the process of cell proliferation.
Hypofunction of glycogen degradation is a subtype of hypofunction of decomposing: A process that performs a decreased or insufficient glycogen degradation.
A role played by the entity which enables the facilitated diffusion of a calcium ion (by an energy-independent process) involving passage through a transmembrane aqueous pore or channel without evidence for a carrier-mediated mechanism.
Activation and oligomerization of BAK protein is a subtype of molecular subpathway. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
Activation and oligomerization of BAK protein [cell death]
A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.
GLUTATHIONE (canonical)[Glutathione depletion]
Glutathione peroxidase 1 [Glutathione depletion]
GLUTATHIONE peroxidase (canonical)[Glutathione depletion]
CASPASE 3 (canonical)[Glutathione depletion]
Inflammatory response is a subtype of changing material: The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
inflammatory response [Glutathione depletion]
Hepatic fibrosis is a subtype of fibrosis: A process that replaces liver tissues to fibrous connective tissues, usually as a consequence of inflammation or other injury. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
hepatic fibrosis [Glutathione depletion]
CYP2E1 (canonical)[Glutathione depletion]
CYP3A4 (canonical)[Glutathione depletion]
IL-6 - inflammatory cytokine (canonical)[Glutathione depletion]
The chemical reaction resulting in the formation of reactive oxygen species, any molecules or ions formed by the incomplete one-electron reduction of oxygen. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
ROS biosynthetic process [Glutathione depletion]
reactive oxygen species biosynthetic process [Glutathione depletion]
Increasing demand for response to oxidative stress is a subtype of increasing the demand for response to stress: A process that changes the functional demand for the response to the oxidative stress to be higher. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
increasing demand for response to oxidative stress [Glutathione depletion]
Increasing anti-oxidation demand is a subtype of increasing functional demand: A process changes the functional demand of oxidation to be higher. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
increasing anti-oxidation demand [Glutathione depletion]
Increasing anti-oxidation demand is a subtype of increasing functional demand: A process changes the functional demand of oxidation to be higher.
Oxidation-antioxidtion inbalance is a subtype of imbalance: A process that lacks a balance between oxidation and anti-oxidation that inhibits oxidation. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
oxidation-antioxidtion inbalance [Glutathione depletion]
ROS accumulation is a subtype of accumulation of substances in a biological object: A process that keeps ROS (Reactive Oxygen Species) in a biological object. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
ROS accumulation [Glutathione depletion]
ROS accumulation is a subtype of accumulation of substances in a biological object: A process that keeps ROS (Reactive Oxygen Species) in a biological object.
Hyperfunction of peroxisomal fatty acid beta-oxidation is a subtype of hyperfunction of fatty acid beta-oxidation: A process that performs an excessive peroxisomal fatty acid beta-oxidation. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
hyperfunction of peroxisomal fatty acid beta-oxidation [Glutathione depletion]
The chemical reaction resulting in the formation of ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
ATP biosynthetic process [Glutathione depletion]
Iron accumulation is a subtype of accumulation of substances in a biological object: A process that keeps iron in an organism, tissue, organelle, or cell.
Iron accumulation is a subtype of accumulation of substances in a biological object: A process that keeps iron in an organism, tissue, organelle, or cell. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
iron accumulation [Glutathione depletion]
Kupffer cell activation is a subtype of macrophage activation: A change in morphology and behavior of a kupffer cell resulting from exposure to a cytokine, chemokine, cellular ligand, or soluble factor.
Kupffer cell activation is a subtype of macrophage activation: A change in morphology and behavior of a kupffer cell resulting from exposure to a cytokine, chemokine, cellular ligand, or soluble factor. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
Chronic ethanol exposure increases the gut permeability, resulting in translocation of gut endotoxin/LPS to liver. In liver, LPS leads to KCs activation via activating NOX and the TLR-4 pathway. The activated KCs then produce a large amount of reactive oxygen species (ROS), pro-inflammatory cytokines, and chemokines, which finally lead to liver injury
kupffer cell activation [Glutathione depletion]
Accumulation of ethanol in intestine is a subtype of accumulation of xenobiotics: A process that keeps ethanol in the intestine. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
accumulation of ethanol in intestine [Glutathione depletion]
Accumulation of ethanol in intestine is a subtype of accumulation of xenobiotics: A process that keeps ethanol in the intestine.
LPS translocation from gut to liver is a subtype of transmitting: A process that of the directed movement of LPS from the gut to the liver.
LPS translocation from gut to liver is a subtype of transmitting: A process that of the directed movement of LPS from the gut to the liver. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
LPS translocation from gut to liver [Glutathione depletion]
IL-1B (canonical)[Glutathione depletion]
IL-10 (canonical)[Glutathione depletion]
TNF-A (canonical)[Glutathione depletion]
Cell death dependent molecule is a subtype of toxic course dependent chemical entity. This gene can participate in the course of cell death as a gene product. Gene profile:caonical that described in textbooks or articles.
cell death dependent dependent molecule (canonical)
Negative regulation of inflammatory response is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of inflammatory response. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
negative regulation of inflammatory response [Eosinophilic granular degeneration]
Inflammatory cytokine gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature inflammatory cytokine gene product or products (proteins or RNA). This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
inflammatory cytokine gene expression [Glutathione depletion]
A pathologic process that involves the transformation of normal cells to a neoplastic state and resulting in polyclonal or monoclonal neoplastic cell proliferation. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
Lipid storage in liver is a subtype of lipid storage: The accumulation and maintenance in cells or tissues of lipids in the liver. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
Hepatic fibrosis is a subtype of fibrosis: A process that replaces liver tissues to fibrous connective tissues, usually as a consequence of inflammation or other injury. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
Liver dysfunction is a subtype of dysfunctioning: A process that performs an abnormal and incomplete liver function. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
Phospholipidosis dependent molecule is a subtype of toxic course dependent chemical entity. This gene can participate in the course of phospholipidosis as a gene product. Gene profile:caonical that described in textbooks or articles.
phospholipidosis dependent molecule (canonical)
Osgin1 - apotosis inducing factor (rat)[Cell death]
Osgin1 - cancer repressor (rat)[Cell death]
Osgin1 - oxidative stress response protein (rat)[Cell death]
TP53 - apotosis inducing factor (canonical)[Cell death]
Negative regulation of cytokine gene expression is a subtype of negative regulation of gene expression: A process that stops, prevents, or reduces the frequency, rate or extent of inflammatory cytokine gene expression.
negative regulation of cytokine gene expression
The selective autophagy process in which a peroxisome is degraded by macroautophagy. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
pexophagy [Eosinophilic granular degeneration]
Autophagy of peroxisomes (pexophagy) is provided by ATM phosphorylation of PEX5 at Ser141, which promotes PEX5 mono-ubiquitination at K209, and recognition of ubiquitinated PEX5 by the autophagy adapter protein p62, directing the autophagosome to peroxisomes to induce pexophagy.
A role played by the entity that competitively inhibits the catalysis of the hydrolysis of a phospholipid.
AMPK is a highly evolutionarily conserved serine/threonine kinase, and orthologs of the AMPK subunits are found in all eukaryotic species. At the molecular level, AMPK is a heterotrimer complex comprising a catalytic alpha subunit, with a conventional serine/threonine protein kinase domain, and two regulatory subunits, beta and gamma. In mammals, each subunit is encoded by multiple genes (alpha1, alpha2, beta1, beta2, gamma1, gamma2, gamma3), which results in 12 possible combinations of AMPK complex.
A set or series of molecular interactions.
A combining role with a signal and transmitting the signal to the transcriptional machinery by interacting selectively and non-covalently with a specific DNA sequence in order to modulate transcription by RNA polymerase II.
hasrelated molecular function GO:0004879
imipramine - apotosis inducing factor [Phospholipidosis]
Induction of apoptosis by cationic amphiphilic drugs amiodarone and imipramine. Drugs that induce this disease often share common physiochemical properties and are collectively classified as cationic amphiphilic drugs (CADs). Phosospholipids, which were significantly increased in drug-treated cells. Cell number in amiodarone (10 microg/mL) and imipramine (20 microg/mL) cultures following the 96-h incubation period were markedly reduced compared to control cultures. These observations suggested that accumulation of cellular phospholipids could inhibit cell proliferation. Disruption of cell lysosomes in U-937 cells following accumulation of phospholipids does not cause a cell cycle arrest but instead induces apoptosis by activation of caspase pathways.
amiodarone - apotosis inducing factor [Phospholipidosis]
Treating both B-13 and B-13/H cells with the drug amiodarone, which has been reported to induce phospholipidosis in variety of cell types, induced phospholipidosis – most markedly in B-13/H cells.
amiodarone - phospholipase competition inhibitor [Phospholipidosis]
imipramine - phospholipase competition inhibitor [Phospholipidosis]
AKT - cell proliferation promoting factor (canonical)[Phospholipidosis]
A role played by the entity which involves in regulating a process.
Any process that modulates the rate or extent of progression through the cell cycle. This entity is a specific course-dependent process. This process can constitute the course of eosinogranular dgeneration.
regulation of cell cycle [Eosinophilic granular degeneration]
Tumor cell proliferation is a subtype of cell proliferation: A process of the multiplication or reproduction of tumor cells, resulting in the rapid expansion of a tumor cell population. This entity is a specific course-dependent process. This process can constitute the course of Eosinogranular degeneration.
tumor cell proliferation [Eosinophilic granular degeneration]
The totality of all processes through which increasing liver weight is realized.
Liver hypertrophy: a review of adaptive (adverse and non-adverse) changes--conclusions from the 3rd International ESTP Expert Workshop.
The totality of all processes through which eosinogranular degeneration and is realized and finally, tumorigenesis can be occured.
tumorigenesis via eosinophilic granular degeneration [toxic course]
The activation, translocation and oligomerization of BAX involved in the apoptosis. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
Activation, translocation and oligomerization of BAX [cell death]
Intrinsic apoptosis signaling (primitive) is a subtype of signaling [biological]: A processin which an intracellular signal is conveyed to trigger the apoptotic death of a cell. The process starts with reception of an intracellular signal (e.g. DNA damage, endoplasmic reticulum stress, oxidative stress etc.). This process is crucially regulated by permeabilization of the mitochondrial outer membrane (MOMP).
intrinsic apoptosis signaling (primitive)
Cdk1 (mouse)[Eosinophilic granular degeneration]
Cell division protein kinase 4 (EC 2.7.1.- ) (Cyclin-dependent kinase 4) (PSK-J3) (CDK4)
Cdk4(mouse)[Eosinophilic granular degeneration]
Ppara (mouse)[Eosinophilic granular degeneration]
Ppara - cell cycle regulator (mouse)[Eosinophilic granular degeneration]
Myc (mouse)[Eosinophilic granular degeneration]
ACAA1A (human)[Eosinophilic granular degeneration]
Acaa1a (mouse)[Eosinophilic granular degeneration]
Acox1 (mouse)[Eosinophilic granular degeneration]
ACOX1 (human)[Eosinophilic granular degeneration]
Ehhadh (mouse)[Eosinophilic granular degeneration]
we find that induction by PPARα of numerous other peroxisomal genes, including Ehhadh, Pxmp4, Acot4, and Peci, is specific for mouse.
A role played by the entity which enables the transfer of drugs.
ATM (human)[Eosinophilic granular degeneration]
PEX5 (human)[Eosinophilic granular degeneration]
Farnesoid X receptor inactivation is a subtype of inactivating nuclear receptor: A process that changes the activity of the inactivating FxR (farnesoid X receptor) with a nuclear receptor role to be lower.
Hyperfunction of drug transporter gene expression is a subtype of hyperfunction of gene expression: A process that performs an excesssive drug transporter gene expression.
hyperfunction of drug transporter gene expression
Hyperfunction of drug transporter gene expression is a subtype of hyperfunction of gene expression: A process that performs an excesssive drug transporter gene expression. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
hyperfunction of drug transporter gene expression [Ground glass appearance]
Hyperfunction of bile acid transport is a subtype of hyperfunction of transport: A process that performs an excesssive bile acid transport.
Hyperfunction of bile acid transport is a subtype of hyperfunction of transport: A process that performs an excesssive bile acid transport. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
hyperfunction of bile acid transport [Ground glass appearance]
Sgpl1 - lipid metabolism regulator (rat)[Phospholipidosis]
Sgpl1 - tumor cell proliferationregulating factor (mouse) [Phospholipidosis]
Farnesoid X receptor inactivation is a subtype of inactivating nuclear receptor: A process that changes the activity of the activating FxR (farnesoid X receptor) with a nuclear receptor role to be lower. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
Farnesoid X Receptor inactivation [lipidosis]
farnesoid x-activated receptor [lipidosis]
farnesoid x-activated receptor -inactivated state [lipidosis]
FXR -inactivated state (canonical)[lipidosis]
Malfunction of biosynthesis is a subtype of malfunctioning: A process that cannot perform the biosynthesis function appropriately or cannot realize it at all.
Malfunction of lipid biosynthesis is a subtype of malfunctioning: A process that cannot perform the lipid biosynthesis function appropriately or cannot realize it at all.
Hypofunction of phospholipid transport from ER to mitochondrial membrane is a subtype of hypofunction of transport: A process that performs a decreased or insufficient phospholipid transport from ER to mitochondrial membrane.
hypofunction of phospholipid transport from ER to mitochondrial membrane
Hypofunction of phospholipid transport from ER to mitochondrial membrane is a subtype of hypofunction of transport: A process that performs a decreased or insufficient phospholipid transport from ER to mitochondrial membrane. This entity is a specific course-dependent process. This process can constitute the course of ER stress
hypofunction of phospholipid transport from ER to mitochondrial membrane [ER stress]
Increasing liver weight is a subtype of increasing weight: A process that changes the weight of the liver to be higher. This entity is a specific course-dependent process. This process can constitute the course of Hypertrophy.
Malfunction of phospholipid biosynthesis is a subtype of malfunctioning: A process that cannot perform the phospholipid biosynthesis function appropriately or cannot realize it at all.
malfunction of phospholipid biosynthesis
Malfunction of phospholipid biosynthesis is a subtype of malfunctioning: A process that cannot perform the phospholipid biosynthesis function appropriately or cannot realize it at all. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
malfunction of phospholipid biosynthesis [ER stress]
Phospholipidosis dependent molecule is a subtype of toxic course dependent chemical entity. This gene can participate in the course of phospholipidosis as a gene product. Gene profile:Mouse/Liver/
phospholipidosis dependent molecule (mouse)
Increasing liver weight dependent process is a subtype of toxic course dependent process: A process that can constitute the course of liver hypertrophy.
increasing liver weight dependent process
Angiogenin-induced protein kinase B/Akt activation is necessary for angiogenesis but is independent of nuclear translocation of angiogenin in HUVE cells.
Angiogenin secretion from hepatoma cells activates hepatic stellate cells to amplify a self-sustained cycle promoting liver cancer. Hepatocytes release angiogenin extracellularly, which is first taken up by a specific transporter in endothelial and cancer cells, and then undergoes translocation to the nucleus through a phospholipase C dependent mechanism.
Hypofunction of phospholipid degradation is a subtype of hypofunction of decomposing: A process that performs a decreased or insufficient phospholipid degradation. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (moderate).
hypofunction of phospholipid degradation [Phospholipidosis (moderate)]
NPC Intracellular Cholesterol Transporter 1 [Niemann Pick Type C]
NPC Intracellular Cholesterol Transporter 1
NPC Intracellular Cholesterol Transporter 2 [Niemann-Pick Type C]
Because of its ability to bind cholesterol, NPC2 can transfer cholesterol from one liposome to another. This transfer is accelerated in the presence of anionic phospholipids such as bis(monooleoylglycero)phosphate (BMP) and phosphatidyl inositol, which are found in lysosomes
The multiplication or reproduction of cells, resulting in the rapid expansion of a cell population. This entity is a specific course-dependent process. This process can constitute the course of Hypertrophy.
Hypofunction of alcohol metabolism is a subtype of hyperfunctioning: A process that performs a decreased or insufficient glutathione conjugation. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
hypofunction of glutathione conjugation [Glutathione depletion]
Insulin deficiency is a subtype of malfunctioning process: A process that lacks performing the insulin function required. This entity is a specific course-dependent process. This process can constitute the course of diabetes.
Increasing blood glucose level is a subtype of increasing concentration: A process that changes the blood glucose concentration in the blood to be higher. This entity is a specific course-dependent process. This process can constitute the course of diabetes.
increasing blood glucose level [diabetes coruse]
The totality of all processes through which a given diabetic retinopathy instance is realized.
Mcrovascular dysfunction is a subtype of organ malfunction: A process that does not perform microvascular function correctly or not functioning at all.
Narrowing of the retinal artery is a subtype of decreasing cross-sectional area: A process that changes the cross-sectional area of the retinal arteries to be smaller.
Narrowing of the retinal artery is a subtype of decreasing cross-sectional area: A process that changes the cross-sectional area of the retinal arteries to be smaller. This entity is a specific course-dependent process. This process can constitute the course of Diabetic retinopathy.
narrowing of the retinal artery [Diabetic retinopathy]
Retinal degeneration is a subtype of changing material: A process that degenerates retinal photoreceptors and pigmented epithelial cells. This entity is a specific course-dependent process. This process can constitute the course of Diabetic retinopathy.
retinal degeneration [Diabetic retinopathy]
Any process that modulates the rate or extent of progression through the cell cycle. This entity is a specific course-dependent process. This process can constitute the course of Hypertrophy.
Increasing hepatocellular volume is a changing process to change the volume of the hepatocyte to increase. This entity is a specific course-dependent process. This process can constitute the course of Hypertrophy.
increasing hepatocellular volume [Hypertrophy]
The process resulting in division and partitioning of components of a cell to form more cells. This entity is a specific course-dependent process. This process can constitute the course of Hypertrophy.
A process of liquid water accumulation in a particular location in an organism, tissue or cell. This entity is a specific course-dependent process. This process can constitute the course of Hypertrophy.
Peroxisomal proliferation in hepatocyte is a subtype of hepatocyte organelle proliferation: A process that becomes larger in the number of peroxisome in hepatocyte(s). This entity is a specific course-dependent process. This process can constitute the course of Hypertrophy.
peroxisomal proliferation in hepatocyte [Hypertrophy]
Mitochondria proliferation in hepatocyte is a subtype of hepatocyte organelle proliferation: A process that becomes larger in the number of mitochondria in hepatocyte(s).
mitochondria proliferation in hepatocyte
Mitochondria proliferation in hepatocyte is a subtype of hepatocyte organelle proliferation: A process that becomes larger in the number of mitochondria in hepatocyte(s). This entity is a specific course-dependent process. This process can constitute the course of Hypertrophy.
mitochondria proliferation in hepatocyte [Hypertrophy]
Hepatocyte organelle proliferation is a subtype of increasing number of organelle: A process that becomes larger in the number of organelles in hepatocyte(s).
Hepatocyte organelle proliferation is a subtype of increasing number of organelle: A process that becomes larger in the number of organelles in hepatocyte(s). This entity is a specific course-dependent process. This process can constitute the course of Hypertrophy.
hepatocyte organelle proliferation [Hypertrophy]
Smooth endoplasmic reticulum proliferation in hepatocyte is a subtype of endoplasmic reticulum proliferation in hepatocyte: A process that becomes larger in the number of smooth endoplasmic reticulum in hepatocyte(s). This entity is a specific course-dependent process. This process can constitute the course of Hypertrophy.
smooth endoplasmic reticulum proliferation in hepatocyte [Hypertrophy]
Increasing osmotic pressure. is a subtype of increasing pressure: A process that changes the osmotic pressure of the object to be higher.
Decreasing osmotic pressure. is a subtype of decresing pressure: A process that changes the osmotic pressure to be lower.
Increasing osmotic pressure in cell is a subtype of increasing osmotic pressure.: A process that changes the osmotic pressure of the cell to be higher.
A process that changes the osmotic pressure of the cell to be higher. This entity is a specific course-dependent process. This process can constitute the course of Hypertrophy.
increasing osmotic pressure in cell [Hypertrophy]
Lipid strorage in hepatocyte is a subtype of lipid storage: A process that keeps lipids in hepatocytes. This entity is a specific course-dependent process. This process can constitute the course of Hypertrophy.
lipid strorage in hepatocyte [Hypertrophy]
Improving is a type of functioning process of meta-function. Both enhancing and improveing represents optional contribution to other function. The “optional” means that the effect of fa is not mandatory to ft, that is, the target function can be performed without improving or enhancing. The discrimination between improving and enhancing is made by whether augmentation of the output can be made without increase of the amount of the input energy or not. For example, the “to make low pressure” of the condenser contributes to the efficiency of the “to generate torque” function without increment of input energy, so its functioning is “Improving”. On the other hand, the “to super-heat” function of the boiler optionally increases the amount of the input energy to make a contribution. Its meta-function is “Enhancing” .
Increasing number of dead cells in liver is a subtype of cell proliferation: A process that becomes larger in the number of dead cells in the liver. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
increasing number of dead cells in liver [Cholestasis]
Accumulation of substance in hepatocyte is a subtype of accumulation of substances in a biological object: A process that keeps substances in the hepatocyte.
Accumulation of substance in hepatocyte is a subtype of accumulation of substances in a biological object: A process that keeps substances in the hepatocyte. This entity is a specific course-dependent process. This process can constitute the course of Hypertrophy.
accumulation of substance in hepatocyte [Hypertrophy]
Decreasing retinal blood flow is a subtype of decreasing flow: A process that changes the amount of retinal flow to be lower.
Moving water to the inside of cell is a subtype of moving A to the inside of B: A process of the movement of water into a cell. This entity is a specific course-dependent process. This process can constitute the course of Hypertrophy.
moving water to the inside of cell [Hypertrophy]
Decreasing retinal blood flow is a subtype of decreasing flow: A process that changes the amount of retinal flow to be lower. This entity is a specific course-dependent process. This process can constitute the course of Diabetic retinopathy.
decreasing retinal blood flow [Diabetic retinopathy]
Moving water to the inside of cell is a subtype of moving A to the inside of B: A process of the movement of water into a cell.
The process in which a cell irreversibly increases in size over time by accretion and biosynthetic production of matter similar to that already present. This entity is a specific course-dependent process. This process can constitute the course of Hypertrophy.
FNDC4 acts as an anti-inflammatory factor on macrophages and improves colitis in mice. Analysis of binding of FNDC4 to different immune cell types reveals strong and specific binding to macrophages and monocytes. FNDC4 treatment of bone marrow-derived macrophages in vitro results in reduced phagocytosis, increased cell survival and reduced proinflammatory chemokine expression. Hence, treatment with FNDC4 results in a state of dampened macrophage activity, while enhancing their survival.
Fibronectin Type III Domain Containing 4 [Phospholipidosis]
FNDC4 acts as an anti-inflammatory factor on macrophages and improves colitis in mice.
Catalysis role of the reaction: N-acylsphingosine + H2O = a fatty acid + sphingosine.
Ligand-dependent and -independent regulation of human hepatic sphingomyelin phosphodiesterase acid-like 3A expression by pregnane X receptor and crosstalk with liver X receptor.
The protein encoded by this gene is part of the clathrin coat assembly complex which links clathrin to receptors in coated vesicles. These vesicles are involved in endocytosis and Golgi processing. This protein, as well as beta-prime-adaptin, gamma-adaptin, and the medium (mu) chain AP47, form the AP-1 assembly protein complex located at the Golgi vesicle. [provided by RefSeq, Jul 2008]
Clathrin-coated vesicles that form on the trans-Golgi network (TGN)1 concentrate newly synthesized lysosomal hydrolases for transport from the Golgi system to the endosome compartment. The endosomes then deliver the hydrolases to the lysosome The formation of clathrin coats depends on the recruitment of the Golgi-specific adaptor protein complex AP-1 onto the cytosolic face of the TGN.
Adaptor Protein Complex AP-1 Subunit Sigma-1A [Phospholipidosis (Sawada)]
Catalysis of the reaction: fatty acid (C-16 or longer) + 2-C = fatty acid (C-16 or longer + 2-C).
Stearoyl-CoA Desaturase [Phospholipidosis]
Catalysis role of the reaction: acyl-CoA + reduced acceptor + O2 = desaturated-acyl-CoA + acceptor + 2 H2O
Catalysis role of the reaction: stearoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+ = oleoyl-CoA + 2 ferricytochrome b5 + H2O.
Selective up-regulation of LXR-regulated genes ABCA1, ABCG1, and APOE in macrophages through increased endogenous synthesis of 24(S),25-epoxycholesterol.
Combining role with a cytokine and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity.
Cholesterol biosynthetic process is a subtype of lipid biosynthetic process: The chemical reaction resulting in the formation of cholesterol, cholest-5-en-3 beta-ol, the principal sterol of vertebrates and the precursor of many steroids, including bile acids and steroid hormones. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
cholesterol biosynthetic process [Phospholipidosis]
Nuclear Receptor Subfamily 0 Group B Member 2 [Phospholipidosis]
Downregulation of nuclear receptor FXR is associated with multiple malignant clinicopathological characteristics in human hepatocellular carcinoma: FXR mRNA level was significantly and positively correlated with the SHP mRNA level in HCC. SHP protein expression in HCC was also found to be dramatically decreased in HCC by immunohistochemistry and Western blot analysis. Thus, suppression of the FXR-SHP pathway may be involved in the tumorigenesis of HCC. LV-FXR-GFP-mediated upregulation of FXR induced SHP expression and inhibited liver cancer cell proliferation in vitro.
At the molecular level, estrogen upregulated hepatic SHP expression through binding to its proximal promoter. In addition, the roles of estrogen were largely blunted in mice with SHP deficiency. These findings reveal a novel role of estrogen in improving hepatosteatosis through upregulation of SHP expression.
This gene encodes a shape change and transformation sensitive actin-binding protein which belongs to the calponin family. It is ubiquitously expressed in vascular and visceral smooth muscle, and is an early marker of smooth muscle differentiation. The encoded protein is thought to be involved in calcium-independent smooth muscle contraction. It acts as a tumor suppressor, and the loss of its expression is an early event in cell transformation and the development of some tumors, coinciding with cellular plasticity. The encoded protein has a domain architecture consisting of an N-terminal calponin homology (CH) domain and a C-terminal calponin-like (CLIK) domain. Mice with a knockout of the orthologous gene are viable and fertile but their vascular smooth muscle cells exhibit alterations in the distribution of the actin filament and changes in cytoskeletal organization. [provided by RefSeq, Aug 2017]
AKT and JNK Signaling Pathways Increase the Metastatic Potential of Colorectal Cancer Cells by Altering Transgelin Expression.
Solute Carrier Family 2 Member 3 [Phospholipidosis]
A lack of available glucose is known to drive cells to increase lipid production for use as fuel. Therefore, repression of SLC2A3 could represent an adaptive response to high in- tracellular lipid levels that could be used preferentially to fulfill energy requirements.
Mammalian Glucose Transporter Activity Is Dependent upon Anionic and Conical Phospholipids he regulated movement of glucose across mammalian cell membranes is mediated by facilitative glucose transporters (GLUTs) embedded in lipid bilayers. Despite the known importance of phospholipids in regulating protein structure and activity, the lipid-induced effects on the GLUTs remain poorly understood. We systematically examined the effects of physiologically relevant phospholipids on glucose transport in liposomes containing purified GLUT4 and GLUT3. The anionic phospholipids, phosphatidic acid, phosphatidylserine, phosphatidylglycerol, and phosphatidylinositol, were found to be essential for transporter function by activating it and stabilizing its structure. Conical lipids, phosphatidylethanolamine and diacylglycerol, enhanced transporter activity up to 3-fold in the presence of anionic phospholipids but did not stabilize protein structure. Kinetic analyses revealed that both lipids increase the kcat of transport without changing the Km values. These results allowed us to elucidate the activation of GLUT by plasma membrane phospholipids and to extend the field of membrane protein-lipid interactions to the family of structurally and functionally related human solute carriers. KEYWORDS: glucose transport; glucose transport kinetics; glucose transporter type 3 (GLUT3); glucose transporter type 4 (GLUT4); liposome; membrane transporter reconstitution; phospholipid; phospholipid vesicle; protein-lipid interaction
A role played by the entity which enables the transfer of the hexose monosaccharide glucose from one side of a membrane to the other.
This gene encodes the fatty acid binding protein found in liver. Fatty acid binding proteins are a family of small, highly conserved, cytoplasmic proteins that bind long-chain fatty acids and other hydrophobic ligands. This protein and FABP6 (the ileal fatty acid binding protein) are also able to bind bile acids. It is thought that FABPs roles include fatty acid uptake, transport, and metabolism. [provided by RefSeq, Mar 2011]
Fatty Acid Binding Protein 1 [Phospholipidosis]
A role played by the entity which transfers long-chain fatty acids from one side of a membrane to the other. A long-chain fatty acid is a fatty acid with a chain length between C13 and C22
Effect of liver fatty acid binding protein (FABP) T94A missense mutation on plasma lipoprotein responsiveness to treatment with fenofibrate. Fenofibrate, a peroxisome proliferated activated receptor alpha (PPARalpha) agonist, has been shown to decrease plasma triglyceride (TG) and increase plasma high-density lipoprotein (HDL) cholesterol levels despite a large interindividual variation in the response. Fenofibrate-activated PPARalpha binds to a DNA sequence element termed PPAR response element (PPRE) present in regulatory regions of target genes. A PPRE has been identified in the proximal 5' flanking region of the gene encoding the liver fatty acid binding protein (LFABP). LFABP is a small cytosolic protein of 14 kDa present in the liver and the intestine and is a member of the superfamily of the fatty acid binding proteins (FABPs). FABPs play a role in the solubilization of long-chain fatty acids (LCFAs) and their CoA-ester to various intracellular organelles. FABPs serves as intracellular acceptors of LCFAs, and they may also have an impact in ligand-dependent transactivation of PPARs in trafficking LCFAs to the nucleus. Since PPARs are known to regulate the transcription of many genes involved in lipid metabolism, the importance of LFABP in fatty acid uptake has to be considered. The aim of this study was to verify whether genetic variations in the LFABP gene may impact on plasma lipoprotein/lipid levels in the fasting state as well as on the response to a lipid-lowering therapy with fenofibrate on plasma lipids and obesity variables. We also wanted to verify whether the presence of the PPARalpha L162V mutation interacts with genetic variants in LFABP gene. To achieve this goal, we first determined the genomic structure of the human LFABP gene and then designed intronic primers to sequence the coding regions, all exon-intron splicing boundaries, and the promoter region of the gene in 24 patients showing divergent plasma lipoprotein/lipid response to fenofibrate. Sequence analysis revealed the presence of a T94A missense mutation in exon 3. Interspecies comparison revealed that threonine 94 is conserved among species. We subsequently screened another sample of 130 French Canadian subjects treated with fenofibrate for the presence of the LFABP T94A mutation. Carriers of the A94 allele were at increased risk to exhibit plasma TG levels above 2.00 mmol/l after treatment with fenofibrate [2.75 (1.03-7.34); OR 95% confidence interval (CI)]. In addition, carriers of the A94 allele were characterized by higher baseline plasma-free fatty acid levels (FFA) ( p=0.01) and by a lower body mass index (BMI) ( p=0.05) and waist circumference ( p=0.005) than T94 homozygotes. Moreover, PPARalpha L162V and LFABP T94A showed to have a synergistic effect on BMI ( p interaction = 0.03). These results suggest that the LFABP T94A missense mutation could influence obesity indices as well as the risk to exhibit residual hypertriglyceridmia following a lipid-lowering therapy with fenofibrate.
The protein encoded by this gene is a plasma protease inhibitor and member of the serine protease inhibitor class. Polymorphisms in this protein appear to be tissue specific and influence protease targeting. Variations in this protein's sequence have been implicated in Alzheimer's disease, and deficiency of this protein has been associated with liver disease. Mutations have been identified in patients with Parkinson disease and chronic obstructive pulmonary disease. [provided by RefSeq, Jul 2008]
http://omim.org/entry/107280 Alpha-1-antichymotrypsin is a plasma protease inhibitor synthesized in the liver.
Increasing blood glucose lebvel is a subtype of increasing concentration: A process that changes the blood glucose concentration in the blood to be higher. This entity is a specific course-dependent process. This process can constitute the course of Diabetic retinopathy.
increasing blood glucose level [Diabetic retinopathy]
Liver X receptor agonists inhibit tissue factor expression in macrophages.
Ethanol-induced liver injury: potential roles for egr-1.
E2F1 is a novel fibrogenic gene that regulates cholestatic liver fibrosis through the Egr-1/SHP/EID1 network.
ATF3 epigenetically suppresses expression of EGR-1, a non-canonical pro-inflammatory transcriptional modulator crucial to cancer chemokine induction.
Loss of Egr-1 sensitizes pancreatic beta-cells to palmitate-induced ER stress and apoptosis.
Role of early growth response 1 in liver metabolism and liver cancer.
Diabetes dependent process is a subtype of disease course dependent process: A process that can constitute the course of diabetes.
Diabetes dependent process [diabetes course]
Process of binding by which electrophiles interact with DNA (deoxyribonucleic acid).
Process of binding by which electrophiles interact with DNA (deoxyribonucleic acid). This entity is a specific course-dependent process. This process can constitute the course of Cell death.
binding to DNA by electrophiles [cell death]
Substance with substance with cationic amphiphilic drug role is a subtype of substance with role. This entity is participating in a phospholipidosis and playing a cationic amphiphilic drug role.
Linoleic acid (LA) metabolism，Fatty acid metabolism
The protein encoded by this gene is a member of the fatty acid desaturase (FADS) gene family. Desaturase enzymes regulate unsaturation of fatty acids through the introduction of double bonds between defined carbons of the fatty acyl chain. FADS family members are considered fusion products composed of an N-terminal cytochrome b5-like domain and a C-terminal multiple membrane-spanning desaturase portion, both of which are characterized by conserved histidine motifs. This gene is clustered with family members at 11q12-q13.1; this cluster is thought to have arisen evolutionarily from gene duplication based on its similar exon/intron organization. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]
Delta-6 Fatty Acid Desaturase [Phospholipidosis]
Fatty Acid Desaturase 2 Delta-6 Fatty Acid Desaturase [Phospholipidosis]
Identification of intracellular carriers for the endocannabinoid anandamide. The endocannabinoid anandamide (arachidonoyl ethanolamide, AEA) is an uncharged neuromodulatory lipid that, similar to many neurotransmitters, is inactivated through its cellular uptake and subsequent catabolism. AEA is hydrolyzed by fatty acid amide hydrolase (FAAH), an enzyme localized on the endoplasmic reticulum. Three fatty acid binding proteins (FABPs) known to be expressed in brain were examined as possible intracellular AEA carriers. FABPs represent the first proteins known to transport AEA from the plasma membrane to FAAH for inactivation and may therefore be novel pharmacological targets.
Survival of tissue-resident memory T cells requires exogenous lipid uptake and metabolism. Increased FABP4 and FABP5 expression and enhanced extracellular FFA uptake were also demonstrated in human CD8+ TRM cells in normal and psoriatic skin. These results suggest that FABP4 and FABP5 have a critical role in the maintenance, longevity and function of CD8+ TRM cells, and suggest that CD8+ TRM cells use exogenous FFAs and their oxidative metabolism to persist in tissue and to mediate protective immunity.
Fatty acid-binding protein 5 function in hepatocellular carcinoma through induction of epithelial-mesenchymal transition.
Catalysis role of the reaction: linoleoyl-CoA + reduced acceptor + O2 = gamma-linolenoyl-CoA + acceptor + 2 H2O.
S1P[Phospholipidosis - tumor proliferation]
This gene encodes a member of the acid ceramidase family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. Processing of this preproprotein generates alpha and beta subunits that heterodimerize to form the mature lysosomal enzyme, which catalyzes the degradation of ceramide into sphingosine and free fatty acid. This enzyme is overexpressed in multiple human cancers and may play a role in cancer progression. Mutations in this gene are associated with the lysosomal storage disorder, Farber lipogranulomatosis, and a neuromuscular disorder, spinal muscular atrophy with progressive myoclonic epilepsy. [provided by RefSeq, Oct 2015]
ASAH1 (human)[Phospholipidosis - insulin resistance inhibition]
A role played by the entity that ihibits the insulin resistance.
Negative regulation of increasing insulin resistance is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of insulin resistance. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
negative regulation of increasing insulin resistance [Phospholipidosis]
Substance with substance with cationic amphiphilic drug role is a subtype of substance with role. This entity is participating in a biological process and playing a cationic amphiphilic drug role.
substance with cationic amphiphilic drug role
lysosomal enzyme transport to lysosome is a subtype of transport: A process that of the transfer of a lysosomal enzyme (from the ribosome to the lysosome). This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
lysosomal enzyme transport (to lysosome) [Phospholipidosis]
lysosomal enzyme transport (from ribosome to lysosome) is a subtype of transport: A process that of the transfer of a lysosomal enzyme (from the ribosome to the lysosome).
transportng lysosomal enzyme from ribosome to lysosome
Phospholipidosis (normal course) is a subtype of process sequences: The courses of processes through which phospholipid homeostasis balance is keeping.
Keeping amount of phospholipid in lysosome is a subtype of keeping amount: A process that maintaining the amount of lysosomal phospholipid.
keeping amount of phospholipid in lysosome
Keeping amount of phospholipid in lysosome is a subtype of keeping amount: A process that maintaining the amount of lysosomal phospholipid. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
keeping amount of phospholipid in lysosome [Phospholipidosis]
The totality of all processes through which the phospholipidosis is realized. The severity is mild.
Dysfunction of fatty acid degradation is a subtype of hypofunctioning: A process that performs a decreased or insufficient lipid degradation. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
dysfunction of fatty acid degradation [Lipidosis]
CAD insertion into phospholipase binding site to lysosomal inner membrane is a subtype of binding: A process that CAD inserts and replaces the phospholipase binding site in the lysosomal inner membrane. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (mild).
CAD insertion into phospholipase binding site to lysosomal inner membrane [Phospholipidosis (mild)]
Forming a complex of CAD and phospholipid is a subtype of forming a complex of drugs and biological substance: A process that forms a complex consisiting phospholipids and CAD (Cationic Amphiphilic Drug) in the lysosomal membrane, which causes structural change of the membrane. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
forming a complex of CAD and phospholipid [Phospholipidosis]
Forming a complex of CAD (Cationic Amphiphilic Drugs) and phospholipid is a subtype of forming a complex of drugs and biological substance: A process that forms a complex consisiting phospholipids and CAD in the lysosomal membrane, which causes structural change of the membrane.
CAD decreases phospholipid release for cell membrane repair from lysosome.
forming a complex of CAD and phospholipid
Forming a complex of CAD and phospholipid is a subtype of forming a complex of drugs and biological substance: A process that forms a complex consisiting phospholipids and CAD (Cationic Amphiphilic Drugs cationic amphiphile drug) in the lysosomal membrane, which causes structural change of the membrane. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
forming a complex of CAD and phospholipid [Phospholipidosis (severe) ]
Hypofunction of phospholipid export from lysosome is a subtype of hypofunction of export: A process that performs a decreased or insufficient phospholipid export from lysosome. And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (moderate).
hypofunction of phospholipid export from lysosome [Phospholipidosis (moderate) ]
CAD accumulation in lysosome is a subtype of compound accumulation in lysosome: A process that keeps CAD (Cationic Amphiphilic Drug) in the lysosome. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
CAD accumulation in lysosome [Phospholipidosis]
CAD insertion into phospholipase binding site to lysosomal inner membrane is a subtype of binding: A process that CAD inserts and replaces the phospholipase binding site in the lysosomal inner membrane. And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (moderate).
CAD insertion into phospholipase binding site to lysosomal inner membrane [Phospholipidosis (moderate) ]
The totality of all processes through which the phospholipidosis is realized. The severity is moderate.
Phospholipid homeostasis imbalance is a subtype of lipid homeostasis imbalance: A process that becomes lacking a phospholipid homeostastasis balance. And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (moderate).
phospholipid homeostasis imbalance [Phospholipidosis (moderate) ]
Phospholipid accumulation in lysosome is a subtype of phospholipid accumulation: A process that keeps phospholipid in the lysosome. And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (moderate).
phospholipid accumulation in lysosome [Phospholipidosis (moderate) ]
Phospholipid metabolism imbalance is a subtype of imbalance: A process that becomes lacking a homeostastasis balance of phospholipid metabolism. And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (moderate).
phospholipid metabolism imbalance [Phospholipidosis (moderate) ]
Glycerophospholipid accumulation in lysosome is a subtype of phospholipid accumulation in lysosome: A process that keeps glycerophospholipid in the lysosome. And the degree is moderate. This process is dependent on the glycerophospholipid disorder (moderate) and can constitute the course of Phospholipidosis.
glycerophospholipid accumulation in lysosome [Phospholipidosis - glycerophospholipid disorder ]
A process that keeps phosphatidylinositol in the lysosome. This process can constitute the course of Phospholipidosis (phosphatidylinositol disorder ).
phosphatidylinositol accumulation in lysosome [Phospholipidosis - phosphatidylinositol disorder]
A process that keeps phosphatidylethanolamine in the lysosome. This process can constitute the course of Phospholipidosis (phosphatidylethanolamine disorder).
phosphatidylethanolamine accumulation in lysosome [Phospholipidosis - phosphatidylethanolamine disorder]
A process that keeps phosphatidylglycerol in the lysosome. This process can constitute the course of Phospholipidosis (phosphatidylglycerol disorder ).
phosphatidylglycerol accumulation in lysosome [Phospholipidosis - phosphatidylglycerol disorder]
A process that keeps phosphatidylcholine in the lysosome. This process can constitute the course of Phospholipidosis (phosphatidylethanolamine disorder).
phosphatidylcholine accumulation in lysosome [Phospholipidosis - phosphatidylcholine disorder]
A process that keeps phosphatidylserine in the lysosome. This process can constitute the course of Phospholipidosis (phosphatidylserine disorder).
phosphatidylserine accumulation in lysosome [Phospholipidosis - phosphatidylserine disorder ]
A process that keeps phosphatidic acid in the lysosome. This process can constitute the course of Phospholipidosis phosphatidic acid disorder).
phosphatidic acid accumulation in lysosome [Phospholipidosis - phosphatidic acid disorder]
SGPL1 - apoptosis inducer (human)[Phospholipidosis]
Sphingomyelin accumulation in lysosome is a subtype of phospholipid accumulation in lysosome: A process that keeps sphingomyelin in the lysosome. This process can constitute the course of sphingomyelin disorder.
sphingomyelin accumulation in lysosome [Phospholipidosis - sphingomyelin disorder ]
Phosphoipidosis is a subtype of process sequences: The courses of processes through which phospholipidosis is realized.
Phosholipase gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature phospholipase gene product or products (proteins or RNA).
Phosholipase gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature phospholipase gene product or products (proteins or RNA). This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
phosholipase gene expression [Phospholipidosis]
Hyperfunction of phospholipid synthesis gene expression is a subtype of hyperfunction of gene expression: A process that performs an excesssive phospholipid synthetic gene expression. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (normal condition).
hyperfunction of phospholipid synthesis gene expression [Phospholipidosis - normal]
Increasing phospholipid is a subtype of increasing quantity: A process that changes the amount of phospholipid to be larger. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (normal condition).
increasing phospholipid [Phospholipidosis (normal condition)]
The chemical reactions and pathways resulting in the formation of phospholipids, any lipid containing phosphoric acid as a mono- or diester. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
phospholipid biosynthetic process [Phospholipidosis(normal)]
Phospholipid transport from lysosome into cytosol is a subtype of phospholipid transfer to membrane: A process of the transfer of a phospholipid from the lysosome to the plasma membrane.
Decreasing number of cells is a subtype of decreasing number of objects: A process that becomes smaller in number of cells. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
decreasing number of cells [Phospholipidosis]
A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
Hyperfunctioning of apoptotic process is a subtype of hyperfunctioning: A process that performs an excesssive apoptosis.
Decreasing number of lysosomes is a subtype of decreasing number of objects: A process that becomes smaller in number of lysosomes.
Decreasing number of lysosomes is a subtype of decreasing number of objects: A process that becomes smaller in number of lysosomes. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
decreasing number of lysosomes [Phospholipidosis]
Removing phospholipid by Kupffer cell or macrophage is a subtype of removing: A process that takes a phospholipid from a cell by Kupffer cells or macrophages . This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (normal condition).
removing phospholipid by Kupffer cell or macrophage [Phospholipidosis]
Removing phospholipid by Kupffer cell or macrophage is a subtype of removing: A process that takes a phospholipid from a cell by Kupffer cells or macrophages .
removing phospholipid by Kupffer cell or macrophage
Phospholipid synthesis gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature phospholipid synthesis gene product or products (proteins or RNA). This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
phospholipid synthesis gene expression [Phospholipidosis]
Phospholipid synthesis gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature phospholipid synthesis gene product or products (proteins or RNA).
Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of phospholipids. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis(normal condition).
positive regulation of phospholipid biosynthetic process [Phospholipidosis (normal)]
Moving phopholipid to lysosome is a subtype of moving A to the inside of B: A process that of the movement of phospholipids into lysosomes. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
moving phopholipid to lysosome [Phospholipidosis]
Moving phopholipid to lysosome is a subtype of moving A to the inside of B: A process that of the movement of phospholipids into lysosomes.
Increasing phospholipid material is a subtype of increasing quantity: A process that changes the amount of phospholipid material to be larger. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosisb(normal condition).
increasing phospholipid material (normal condition) [Phospholipidosis]
Phosphholipid binding by phospholipase is a subtype of phospholipid binding: Interacting selectively and non-covalently with phospholipids byphospholipases. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis(normal condition).
phosphholipid binding by phospholipase [Phospholipidosis]
IL-2 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the cytokine IL-2. This process is dependent on the inflammation and can constitute the course of Phospholipidosis (excessive defense) .
IL-2 signaling (primitive) [Phospholipidosis (excessive defense) - inflammation ]
IL-2 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the cytokine IL-2. This process is dependent on the apoptosis inhibition and can constitute the course of Phospholipidosis (excessive defense) .
IL-2 signaling (primitive) [Phospholipidosis (excessive defense) - apoptosis inhibition ]
IL-2 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the cytokine IL-2. This process is dependent on the cell cycle arrest and can constitute the course of Phospholipidosis (excessive defense) .
IL-2 signaling (primitive) [Phospholipidosis (excessive defense) - cell cycle arrest ]
interleukin 2 receptor, beta [Phospholipidosis - inflammation]
IL2RB (human)[Phospholipidosis - inflammation]
New role for Shc in activation of the phosphatidylinositol 3-kinase/Akt pathway. Experiments with the chimeric receptors indicate that Shc also signals to the PI-3K/Akt pathway in response to IL-2. Our results suggest that cytokine receptors lacking direct PI-3K binding sites activate Akt via a Shc/Grb2/Gab2/PI-3K pathway, thereby regulating cell survival and/or proliferation.
PPARA - glucose metabolism regulator (canonical)[Eosinophilic granular degeneration]
Phospholipid hydrolysis is a subtype of hydrolysis: A chemical reaction that uses water to break down a phospholipid. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
phospholipase activity http://purl.obolibrary.org/obo/GO_0004620
phospholipid hydrolysis [Phospholipidosis]
Phospholipid hydrolysis is a subtype of hydrolysis: A chemical reaction that uses water to break down a phospholipid.
A process that stops, prevents, or reduces the frequency, rate or extent of phospholipid hydrolysis mildly. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (mild).
negative regulation of phospholipid hydrolysis [Phospholipidosis (mild)]
Negative regulation of phospholipid degradation is a subtype of negative regulation of phospholipid hydrolysis: A process that stops, prevents, or reduces the frequency, rate or extent of phospholipid hydrolysis.
negative regulation of phospholipid hydrolysis
Negative regulation of phospholipase-mediated phospholipid degradation by CAD is a subtype of negative regulation of phospholipid degradation: A process that stops, prevents, or reduces the frequency, rate or extent of phospholipase-mediated phospholipid deradation regulated by CAD. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
negative regulation of phospholipase-mediated phospholipid degradation by CAD [Phospholipidosis]
AKT signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal transmitted by the intracellular serine/threonine kinase protein kinase B (also called AKT). This process is dependent on the cell proliferation and can constitute the course of Phospholipidosis (excessive defense) .
AKT signaling (primitive) [phospholipidosis (excessive defense) - cell proliferation ]
AKT signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal transmitted by the intracellular serine/threonine kinase protein kinase B (also called AKT). This process is dependent on the tumor cell proliferation and can constitute the course of Phospholipidosis (excessive defense) .
AKT signaling (primitive) [Phospholipidosis (excessive defense) - tumor cell proliferation ]
AKT - tumor cell proliferation promoting factor (canonical)[Phospholipidosis]
Phosphatidylinositol 3-kinase signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal transmitted by the phosphatidylinositol 3-kinase (PI3K). This process is dependent on the cell proliferation and can constitute the course of Phospholipidosis (excessive defense) .
phosphatidylinositol 3-kinase signaling (primitive) [Phospholipidosis (excessive defense) - cell proliferation ]
PI3K - cell proliferation promoting factor (canonical)[Phospholipidosis]
PI3K - tumor cell proliferation promoting factor (canonical)[Phospholipidosis]
Phosphatidylinositol 3-kinase signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal transmitted by the phosphatidylinositol 3-kinase (PI3K). This process is dependent on the tumor cell proliferation and can constitute the course of Phospholipidosis (excessive defense) .
phosphatidylinositol 3-kinase signaling (primitive) [Phospholipidosis (excessive defense) - tumor cell proliferation ]
EGFR signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal transmitted by the EGFR (epidermal growth factor receptor) on the surface of a cell, starting with a ligand binding to a EGFR This process is dependent on the cell proliferation and can constitute the course of Phospholipidosis (excessive defense) .
EGFR signaling (primitive) [Phospholipidosis (excessive defense) - cell proliferation ]
EGFR signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal transmitted by the EGFR (epidermal growth factor receptor) on the surface of a cell, starting with a ligand binding to a EGFR This process is dependent on the tumor cell proliferation and can constitute the course of Phospholipidosis (excessive defense) .
EGFR signaling (primitive) [Phospholipidosis (excessive defense) - tumor cell proliferation ]
EGFR (canonical)[Phospholipidosis - cell proliferation factor]
EGFR (canonical)[Phospholipidosis - tumor cell proliferation factor]
IL2 (canonical)[Phospholipidosis - inflammatory cytokine]
IL2 (canonical)[Phospholipidosis - apotosis inhibitor]
IL2 (canonical)[Phospholipidosis - tumor cell proliferation promoting factor]
IL2 (canonical)[Phospholipidosis - cell cycle progression promoting factor]
Kupffer cell differentiation is a subtype of macrophage differentiation: The process that acquires the specialized features of a kupffer cell.
The process in which a relatively unspecialized monocyte acquires the specialized features of a Kupffer cell.
Hyperfunction of phospholipid phagocytosis by Kupffer cells is a subtype of hyperfunctioning: A process that performs an excessive phospholipid phagocytosis by Kupffer cells. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense).
hyperfunction of phospholipid phagocytosis by Kupffer cells [Phospholipidosis (excessive defense)]
Hyperfunction of phospholipid phagocytosis by Kupffer cells is a subtype of hyperfunctioning: A process that performs an excessive phospholipid phagocytosis by Kupffer cells.
hyperfunction of phospholipid phagocytosis by Kupffer cells
Hyperfunction of cell differentiation is a subtype of hyperfunctioning: A process that performs an excesssive cell differentiation.
Hyperfunction of Kupffer cell differentiation is a subtype of hyperfunction of cell differentiation: A process that performs an excesssive kupffer cell differentiation.
hyperfunction of Kupffer cell differentiation
Phospholipid homeostasis imbalance is a subtype of lipid homeostasis imbalance: A process that becomes lacking a phospholipid homeostastasis balance. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
phospholipid homeostasis imbalance [Phospholipidosis (severe) ]
Decreasing lysosomal membrane permeability is a subtype of decreasing membrane permeability: A process that changes the permeability of the lysosomal membrane to be lower. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
decreasing lysosomal membrane permeability [Phospholipidosis]
Decreasing lysosomal membrane permeability is a subtype of decreasing membrane permeability: A process that changes the permeability of the lysosomal membrane to be lower.
decreasing lysosomal membrane permeability
Decreasing membrane permeability is a subtype of changing permeability: A process that changes the permeability of the membrane to be lower.
Hyperfunction of phospholipid material transport is a subtype of hyperfunction of transport: A process that performs an excesssive phospholipid material transport.
hyperfunction of phospholipid material transport
Combining role with a pathogen-associated molecular pattern (PAMP), a structure conserved among microbial species, or damage-associated molecular pattern (DAMP), an endogenous molecule released from damaged cells), to initiate a change in cell activity.
Receptors of the innate immune system that recognize pathogen associated molecular patterns (PAMPs, e.g. LPS) are called pattern recognition receptors (PRRs).
Negative regulation of phospholipase-mediated phospholipid degradation by CAD is a subtype of negative regulation of phospholipid degradation: A process that stops, prevents, or reduces the frequency, rate or extent of phospholipase-mediated phospholipid deradation regulated by CAD. And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (moderate).
negative regulation of phospholipase-mediated phospholipid degradation by CAD [Phospholipidosis (moderate) ]
A process that stops, prevents, or reduces the frequency, rate or extent of phospholipid hydrolysis moderately. And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (moderate).
negative regulation of phospholipid hydrolysis [Phospholipidosis (moderate) ]
A process that stops, prevents, or reduces the frequency, rate or extent of phospholipid degradation. And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (moderate).
negative regulation of phospholipid degradation [Phospholipidosis (moderate) ]
Hypofunction of ceramide degradation is a subtype of hypofunction of lipid degradation: A process that performs a decreased or insufficient ceramide degradation. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (sphingomyelin disorder).
hypofunction of ceramide degradation [sphingomyelin disorder ]
Negative regulation of phospholipase-mediated phospholipid degradation by CAD is a subtype of negative regulation of phospholipid degradation: A process that stops, prevents, or reduces the frequency, rate or extent of phospholipid deradation by phospholipase.
negative regulation of phospholipase-mediated phospholipid degradation by CAD
A process that stops, prevents, or reduces the frequency, rate or extent of phospholipid hydrolysis severely. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
Phospholipases hydrolyze phospholipids into fatty acids and other lipophilic substances. This entity indicates mainly to the process of inhibiting phospholipases.
negative regulation of phospholipid hydrolysis [Phospholipidosis (severe) ]
Negative regulation of phospholipid hydrolysis is a subtype of negative regulation of phospholipid degradation: A process that stops, prevents, or reduces the frequency, rate or extent of phospholipid hydrolysis. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
negative regulation of phospholipid hydrolysis [Phospholipidosis]
CAD insertion into phospholipase binding site to lysosomal inner membrane is a subtype of binding: A process that CAD inserts and replaces the phospholipase binding site in the lysosomal inner membrane. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
CAD insertion into phospholipase binding site to lysosomal inner membrane [Phospholipidosis (severe) ]
Negative regulation of phospholipase-mediated phospholipid degradation by CAD is a subtype of negative regulation of phospholipid degradation: A process that stops, prevents, or reduces the frequency, rate or extent of phospholipase-mediated phospholipid deradation regulated by CAD. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
negative regulation of phospholipase-mediated phospholipid degradation by CAD [Phospholipidosis (severe) ]
CAD accumulation in lysosome is a subtype of compound accumulation in lysosome: A process that keeps CAD (Cationic Amphiphilic Drugs cationic amphiphile drug) in the lysosome. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
CAD accumulation in lysosome [Phospholipidosis (severe)]
The totality of all processes through which the phospholipidosis is realized. The severity is severe.
Compound accumulation in lysosome is a subtype of accumulation of xenobiotics: A process that keeps compound in the lysosome. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (mild).
compound accumulation in lysosome [Phospholipidosis (mild)]
Compound accumulation in lysosome is a subtype of accumulation of xenobiotics: A process that keeps compound in the lysosome. And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (moderate).
compound accumulation in lysosome [Phospholipidosis (moderate) ]
Negative regulation of cell cycle regulator gene expression is a subtype of negative regulation of gene expression: A process that stops, prevents, or reduces the frequency, rate or extent of cell cycle regulator gene expression.
negative regulation of cell cycle gene expression
ASAH1 - inactivated (human)[Phospholipidosis - hypofunctioning of ceramide degradation]
Increasing hepatic portal pressure is a subtype of increasing pressure: A process that changes the hepatic portal pressure to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatic blood circulatory disorder.
increasing hepatic portal pressure [hepatic blood circulatory disorder]
Increasing hepatic venous pressure is a subtype of increasing pressure: A process that changes the hpatic venous pressure to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatic blood circulatory disorder.
increasing hepatic venous pressure [hepatic blood circulatory disorder]
Hyperfunction of hepatic lymph production is a subtype of hyperfunction of biosynthesis: A process that performs an excessive hepatic lymph production. This entity is a specific course-dependent process. This process can constitute the course of hepatic blood circulatory disorder.
hyperfunction of hepatic lymph production [hepatic blood circulatory disorder]
Hepatic lymph leakage is a subtype of leaking: A process that leaks lymph out from the liver lymphatic vessel. This entity is a specific course-dependent process. This process can constitute the course of hepatic blood circulatory disorder.
hepatic lymph leakage [hepatic blood circulatory disorder]
Ascites (process) is a subtype of accumulation of fluids: A process that keeps fluid in the peritoneal cavity. This entity is a specific course-dependent process. This process can constitute the course of hepatic blood circulatory disorder.
ascites (process) [hepatic blood circulatory disorder]
Inzreasing size of the spleen is a subtype of increasing size: A process that changes the size of the of the spleen to be larger. This entity is a specific course-dependent process. This process can constitute the course of hepatic blood circulatory disorder.
inzreasing size of the spleen [hepatic blood circulatory disorder]
Stomach congestion is a subtype of hyperfunctioning of accumulation: A process that performs an excessive accumulation of blood in the stomach. This entity is a specific course-dependent process. This process can constitute the course of hepatic blood circulatory disorder.
stomach congestion [hepatic blood circulatory disorder]
Intestine congestion is a subtype of hyperfunctioning of accumulation: A process that performs an excessive accumulation of blood in the intestine. This entity is a specific course-dependent process. This process can constitute the course of hepatic blood circulatory disorder.
intestine congestion [hepatic blood circulatory disorder]
Intestine congestion is a subtype of hyperfunctioning of accumulation: A process that performs an excessive accumulation of blood in the intestine.
Bypass formation is a subtype of biological structure formation: A process that constructs an alternate passage of a bodily substancepassage carrying blood. This entity is a specific course-dependent process. This process can constitute the course of hepatic blood circulatory disorder.
bypass formation [hepatic blood circulatory disorder]
Varicosity of veins formation is a subtype of biological structure formation: A process that have a varicosity of veins. This entity is a specific course-dependent process. This process can constitute the course of hepatic blood circulatory disorder.
varicosity of veins formation [hepatic blood circulatory disorder]
Sphingomyelinase gene mutation is a subtype of phopholipase gene mutation: A process that changes the sequence of a sphingomyelinase gene. This entity is a specific course-dependent process. This process can constitute the course of Niemann Pick Disease Type A.
sphingomyelinase gene mutation [Niemann Pick Disease Type A]
Sphingomyelin Phosphodiesterase 1 [Niemann Pick Disease Type A -B]
SMPD1 (canonical)[Niemann Pick Disease Type A -B]
Sphingomyelin Phosphodiesterase 1 [Niemann Pick Disease Type A]
SMPD1 (canonical)[Niemann Pick Disease Type A]
DNAJB9 - apotosis repressor -vitro (human)[ER stress]
DNABJ9 suppresses apoptosis in response to chemotherapeutic agents by forming a negative regulatory loop with p53.
Sphingomyelin Phosphodiesterase 1 [Niemann Pick Disease Type B]
SMPD1 (canonical)[Niemann Pick Disease Type B]
Sphingomyelinase gene mutation is a subtype of phopholipase gene mutation: A process that changes the sequence of a sphingomyelinase gene. This entity is a specific course-dependent process. This process can constitute the course of Niemann Pick Disease Type B.
sphingomyelinase gene mutation [Niemann Pick Disease Type B]
Dysfunction of sphingomyelin degradation is a subtype of dysfunction of phosphosphingolipid degradation: A process that performs an abnormal and incomplete sphingomyelin degradation. This entity is a specific course-dependent process. This process can constitute the course of Niemann Pick Disease Type A.
dysfunction of sphingomyelin degradation [Niemann Pick Disease Type A]
Dysfunction of sphingomyelin degradation is a subtype of dysfunction of phosphosphingolipid degradation: A process that performs an abnormal and incomplete sphingomyelin degradation. This entity is a specific course-dependent process. This process can constitute the course of Niemann Pick Disease Type B.
dysfunction of sphingomyelin degradation [Niemann Pick Disease Type B]
Lipid accumulation in hepatocyte (severe) is a subtype of lipid strorage in hepatocyte: A process that keeps lipids in hepatocytes. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
lipid storage in hepatocyte (severe) [Lipidosis]
lipid accumulation in hepatocyte (severe) [Lipidosis]
Any process that activates, maintains or increases the rate of autophagy. Autophagy is the process in which cells digest parts of their own cytoplasm. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
positive regulation of autophagy [Lipidosis]
Increasing hepatocellular volume is a changing process to change the volume of the hepatocyte to increase. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
increasing hepatocellular volume [Lipidosis]
Hyperfunction of glucose transport to liver is a subtype of hyperfunction of transport: A process that performs an excesssive glucose transport to liver.
hyperfunction of glucose transport to liver
Hyperfunction of glucose transport to liver is a subtype of hyperfunction of transport: A process that performs an excesssive glucose transport to liver. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
hyperfunction of glucose transport to liver [Lipidosis]
Hypofunction of triglyceride transport from hepatocyte to extrahepatic is a subtype of hypofunction of transport: A process that performs a decreased or insufficient triglyceride transport from hepatocyte to extrahepatic.
hypofunction of triglyceride transport from hepatocyte to extrahepatic
Hypofunction of triglyceride transport from hepatocyte to extrahepatic is a subtype of hypofunction of transport: A process that performs a decreased or insufficient triglyceride transport from hepatocyte to extrahepatic. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
hypofunction of triglyceride transport from hepatocyte to extrahepatic [Lipidosis]
HSP90B1 - apotosis repressor -vitro (human)[ER stress]
Triglyceride transport from hepatocyte to extrahepatic is a subtype of triglyceride transport: A process that of the transfer of a triglyceride from the hepatocyte to the exrrahepatic tissues.
triglyceride transport from hepatocyte to extrahepatic
Triglyceride transport from hepatocyte to extrahepatic is a subtype of triglyceride transport: A process that of the transfer of a triglyceride from the hepatocyte to the exrrahepatic tissues. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
triglyceride transport from hepatocyte to extrahepatic [Lipidosis]
Lipid homeostasis imbalance is a subtype of chemical homeostasis imbalance: A process that becomes lacking a lipid homeostastasis balance.
GRP78 - apotosis repressor (canonical)[ER stress]
Tumor cell survial is a subtype of cell survival: A process that keeps the viability of a tumor cell. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Lipid homeostasis imbalance is a subtype of chemical homeostasis imbalance: A process that becomes lacking a lipid homeostastasis balance. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
Increaing in fatty acid inflow into hepatocyte is a subtype of increasing quantity: A process that changes the fatty acid inflow into the hepatocyte to be larger.
increaing in fatty acid inflow into hepatocyte
Increase in lipid inflow into hepatocyte is a subtype of increasing quantity: A process that changes the lipid inflow into the hepatocyte to be larger.
increase in lipid inflow into hepatocyte
Increase in lipid inflow into hepatocyte is a subtype of increasing quantity: A process that changes the lipid inflow into the hepatocyte to be larger. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
increase in lipid inflow into hepatocyte [Lipidosis]
A type of cell death that is morphologically characterized by an increasingly translucent cytoplasm, swelling of organelles, minor ultrastructural modifications of the nucleus (specifically, dilatation of the nuclear membrane and condensation of chromatin into small, irregular, circumscribed patches) and increased cell volume (oncosis), culminating in the disruption of the plasma membrane and subsequent loss of intracellular contents. Necrotic cells do not fragment into discrete corpses as their apoptotic counterparts do. Moreover, their nuclei remain intact and can aggregate and accumulate in necrotic tissues. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
Insulin resistance (process) is a subtype of decreasing sensitivity: A process that changes the sensitivity to the circulating insulin to be lower. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
insulin resistance (process) [Lipidosis]
Insulin deficiency is a subtype of malfunctioning process: A process that lacks performing the insulin function required. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
The totality of all processes through which non-alcoholic fatty liver disease (NAFLD) is realized.
Fatty change [Liver PathologicalFindings] is a type of finding observed in hepatocytes. Lesions are observed as lipid droplets consisting of neutral fat in the hepatocyte based on pathological morphology. This finding is observable in the course of lipidosis.
A metabolic disorder of neutral fat causes fatty change. Lipid droplets consisting of large and small neutral fats (triglycerides) increase in the cytoplasm of hepatocytes. In the case of large lipid droplets, the uneven distribution of nuclei is observed, but in the case of small loose droplets (microvesicular fatty change), uneven distribution of nuclei is not observed. According to the distribution, it classifies into centrilobular, periportal, and diffuse type.
vacuolation [Liver Pathological Findings][Lipidosis]
Eosinophilic granular degeneration [Liver PathologicalFindings] is a type of finding observed in hepatocytes. Lesions are observed in the form that the cytoplasm presents eosinophilic granules based on pathological morphology.
eosinophilic granular degeneration [Liver Pathological Findings]
Hypertrophy [liver findings] is a type of finding observed in the liver. An increase in size (volume) of hepatocytes is observed based on pathological morphology. It is sometimes accompanied by an increase in the number of cells.
hepatocellular hypertrophy [Liver Pathological Findings]
Cholestasis [liver findings] is a type of finding observed in the liver. A pathological findings caused by obstruction in intrahepatic or extrahepatic biliary system. Bile thrombus appears in the intrahepatic bile duct, and in general, bile pigment is observed in hepatocytes and Kupffer cells.
cholestasis [Liver Pathological Findings]
Hyperplasia [ [Liver PathologicalFindings] is a type of finding observed in the liver. An increase in cell number is observed based on pathological morphology.
hyperplasia [Liver Pathological Findings]
Hepatic fibrosis [Liver PathologicalFindings] is a type of finding observed in the liver. Lesions are observed as a proliferation of fibrous tissue in the liver based on pathological morphology.
hepatic fibrosis [Liver Pathological Findings]
Hypofunction of lipoprotein biosynthesis is a subtype of hypofunction of protein synthesis: A process that performs a decreased or insufficient lipoprotein biosynthesis.
hypofunction of lipoprotein biosynthesis
Hypofunction of lipoprotein biosynthesis is a subtype of hypofunction of protein synthesis: A process that performs a decreased or insufficient lipoprotein biosynthesis. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
hypofunction of lipoprotein biosynthesis [Lipidosis]
Lipidosis dependent chemical compound is a subtype of toxic course dependent chemical entity. This entity (drug) can participate in the course of lipidosis.
Increasing demand for response to oxidative stress is a subtype of increasing the demand for stress response : A process that changes the functional demand for the response to the oxidative stress to be higher. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
Because the mitochondrial pathway is saturated, fatty acids are metabolized in peroxisomes, and Cyp2E1 enzyme induction occurs, resulting in oxidative stress.
increasing demand for response to oxidative stress [Lipidosis]
Malfunctioning of cellular membrane is a subtype of malfunctioning process: A process that cannot perform a cellular membrane function appropriately or cannot realize it at all. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
malfunctioning of cellular membrane [Lipidosis]
Cellular membrane lipoperoxidation is a subtype of lipoperoxidation: A process that the degradation of lipids of cellular membrane caused by an oxidative attack from free radicals. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
cellular membrane lipoperoxidation [Lipidosis]
Cellular membrane lipoperoxidation is a subtype of lipoperoxidation: A process that the degradation of lipids of cellular membrane caused by an oxidative attack from free radicals.
Lipoperoxidation is a subtype of lipid oxidation: The degradation of lipids caused by an oxidative attack from free radicals.
Eosinophilic change [Liver PathologicalFindings] is a type of finding observed in hepatocyte cytoplasm. Based on pathological morphology, lesions are stained with eosin.
· Stained with eosinophilic (eosinophilic) dye of hepatic cytoplasm. · Generally, it is caused by diffuse or focal increase of cytoplasmic organelle or excessive accumulation of eosinophilic substance. · Eosinophilic staining area: It often corresponds to mitochondria, smooth endoplasmic reticulum, or peroxisome. · Changes over the entire cytoplasm: granule degeneration, eosinophilic granular change, glute-like change · Cytoplasmic local changes: vitreous, eosinophilic inclusion bodies etc.
eosinophilic change [Liver Pathological Findings]
Lipidosis dependent molecule is a subtype of toxic course dependent chemical entity. This molecule can participate in the course of lipidosis as a gene product. Gene profile:caonical that described in textbooks or articles.
lipidosis dependent molecule (canonical)
The protein encoded by this gene is a major apoprotein of the chylomicron. It binds to a specific liver and peripheral cell receptor, and is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. This gene maps to chromosome 19 in a cluster with the related apolipoprotein C1 and C2 genes. Mutations in this gene result in familial dysbetalipoproteinemia, or type III hyperlipoproteinemia (HLP III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron and VLDL remnants. [provided by RefSeq, Jun 2016]
An affinity inhering in a tissue constituent by virtue of the bearer exhibiting a molecular interaction for acidic dyes under specific ph conditions.
Metabolic intermediate accumulation is a subtype of accumulation of substances in a biological object: A process that keeps intermediate(s) of metabolism in an organism, tissue, organelle, or cell. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
metabolic intermediate accumulation [Glutathione depletion]
A physical attribute inhering in a bearer by virtue of the bearer's rate of doing work.
Ground glass appearance [Liver PathologicalFindings] is a type of finding observed in hepatocyte cytoplasm. Based on the pathological morphology, lesions are observed as a frosted-like change in whole or most of the hepatocytes. This finding is observable in the course of ground glass appearance.
ground glass appearance [Liver Pathological Findings] [Ground glass appearance (course)]
Eosinophilic granular degeneration [Liver PathologicalFindings] is a type of finding observed in hepatocytes. Lesions are observed in the form that the cytoplasm presents eosinophilic granules based on pathological morphology. This finding is observable as a result of increasing peroxisome caused by PPAR.
eosinophilic granular degeneration [Liver Pathological Findings] [eosinogranular degeneration (course) ]
Fatty change [Liver PathologicalFindings] is a type of finding observed in hepatocytes. Lesions are observed as lipid droplets consisting of neutral fat in the hepatocyte based on pathological morphology.
fatty degeneration [Liver PathologicalFindings]
vacuolation [Liver PathologicalFindings]
fatty change [Liver Pathological Findings]
Fatty change [Liver PathologicalFindings] is a type of finding observed in hepatocytes. Lesions are observed as lipid droplets consisting of neutral fat in the hepatocyte based on pathological morphology. This finding is observable in the course of phospholipidosis.
vacuolation [Liver Pathological Findings][Phospholipidosis]
myelin figure in lysosome [Liver Pathological Findings] is a type of finding observed in the liver. Based on pathological morphology, lesions are observed as myelin-like layered structures under electron microscopy. This finding is observable in the course of phospholipidosis.
The presence of phospholipid inclusions are characterized by the presence of cytoplasmic vacuoles seen under the electron microscope as dense cytoplasmic myelin-like bodies showing a concentric lamellar structure with a periodicity of 4-4.5 nm along with an amorphorous matrix within a single membrane-bound lysosomal space. Histopathology of preclinical toxicity studies : interpretation and relevance in drug safety studies, Peter Greaves. 4th ed. Amsterdam ; Boston : Elsevier/AP, 2012.
myelin figure in lysosome [Phospholipidosis]
Moderate accumulation of abnormal proteins in ER is a subtype of accumulation of abnormal proteins in ER: A process that keeps abnormal protein(s) in the ER (endoplasmic reticulum) moderately.
moderate accumulation of abnormal proteins in ER
Severe accumulation of abnormal proteins in ER is a subtype of accumulation of abnormal proteins in ER: A process that keeps abnormal protein(s) in the ER (endoplasmic reticulum) severely.
severe accumulation of abnormal proteins in ER
Sgpl1 - lipid metabolism regulator (mouse)[Phospholipidosis]
Sphingosine 1-phosphate lyase deficiency disrupts lipid homeostasis in liver.
SGPL1 - tumor cell proliferation regulating factor (human) [Phospholipidosis]
Increased mRNA Levels of Sphingosine Kinases and S1P Lyase and Reduced Levels of S1P Were Observed in Hepatocellular Carcinoma in Association with Poorer Differentiation and Earlier Recurrence: The increased expression of SPL (S1P Lyase) mRNA in HCC tissues correlated with poorer HCC differentiation, suggesting that SPL may also play a role in the pathophysiology of HCC. Furthermore, our in vitro study showed that inhibition of SPL expression by siRNA led to reduced proliferation and invasion, while overexpression of SPL caused enhanced proliferation of HCC cell lines. This finding is in direct contrast to data showing that SPL inhibits tumor cell proliferation and survival of colon cancer cells [39]. The role of SPL in tumor cell proliferation may differ in various cell and cancer types (e.g., colon cancer vs. HCC).
Refolding-unfolding imbalance (mild) is a subtype of refolding-unfolding imbalance: A process that lacks a balance between protein refolding and unfolding mildly.
Refolding-unfolding imbalance (moderate) is a subtype of refolding-unfolding imbalance: A process that lacks a balance between protein refolding and unfolding moderately.
refolding-unfolding imbalance (moderate)
A role played by the entity which regulates the process of tumor cell proliferation.
Eosinophilic granular degeneration [Liver PathologicalFindings] is a type of finding observed in hepatocytes. Lesions are observed in the form that the cytoplasm presents eosinophilic granules based on pathological morphology. The degree is mild. This finding is observable as a result of increasing peroxisome caused by PPAR.
eosinophilic granular degeneration [Liver Pathological Findings] [eosinogranular degeneration (mild) ]
Eosinophilic granular degeneration [Liver PathologicalFindings] is a type of finding observed in hepatocytes. Lesions are observed in the form that the cytoplasm presents eosinophilic granules based on pathological morphology. The degree is moderate. This finding is observable as a result of increasing peroxisome caused by PPAR.
eosinophilic granular degeneration [Liver Pathological Findings] [eosinogranular degeneration (moderate) ]
Eosinophilic granular degeneration [Liver PathologicalFindings] is a type of finding observed in hepatocytes. Lesions are observed in the form that the cytoplasm presents eosinophilic granules based on pathological morphology. The degree is severe. This finding is observable as a result of increasing peroxisome caused by PPAR.
eosinophilic granular degeneration [Liver Pathological Findings] [eosinogranular degeneration (severe) ]
Fatty change [Liver PathologicalFindings] is a type of finding observed in hepatocytes. Lesions are observed as lipid droplets consisting of neutral fat in the hepatocyte based on pathological morphology. This finding is observable in the course of lipidosis. The degree is mild.
vacuolation [Liver Pathological Findings][Lipidosis(mild)]
Phosphatidylcholine efflux is a subtype of moving A to the outside of B: A process that excretes phosphatidylcholine to the outside of a cell or organelle.
Fatty change [Liver PathologicalFindings] is a type of finding observed in hepatocytes. Lesions are observed as lipid droplets consisting of neutral fat in the hepatocyte based on pathological morphology. This finding is observable in the course of lipidosis. The degree is moderate.
vacuolation [Liver Pathological Findings][Lipidosis(moderate)]
Fatty change [Liver PathologicalFindings] is a type of finding observed in hepatocytes. Lesions are observed as lipid droplets consisting of neutral fat in the hepatocyte based on pathological morphology. This finding is observable in the course of lipidosis. The degree is severe.
vacuolation [Liver Pathological Findings][Lipidosis(severe)]
Ground glass appearance [Liver PathologicalFindings] is a type of finding observed in hepatocyte cytoplasm. Based on the pathological morphology, lesions are observed as a frosted-like change in whole or most of the hepatocytes. This finding is observable in the course of ground glass appearance. The degree is severe.
ground glass appearance [Liver Pathological Findings] [Ground glass appearance (severe)]
ceramide -apoptosis inducer [Phospholipidosis - positive regulation of apoptosis]
Changing cell survival-cell death balance is a subtype of changing balance: A process that changes the steady state of cell number between cell death and cell survival within an organ or an organism.
changing cell survival-cell death balance
Maintaining cell survival-cell death balance is a subtype of maintaining balance: A process that keeps a balance between cell death and cell survival within an organ or an organism.
maintaining cell survival - cell death balance
Cell survival-cell death imbalance is a subtype is a subtype of imbalance: A process that lacks a balance between cell death and cell survival within an organ or an organism.
Cell survival-cell death imbalance is a subtype is a subtype of imbalance: A process that lacks a balance between cell death and cell survival within an organ or an organism. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
cell survival-cell death imbalance [Phospholipidosis (severe)]
Changing cell survival-cell death balance is a subtype of changing balance: A process that changes the steady state of cell number between cell death and cell survival within an organ or an organism. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
changing cell survival-cell death balance [Phospholipidosis]
Maintaining cell survival-cell death balance is a subtype of maintaining balance: A process that keeps a balance between cell death and cell survival within an organ or an organism. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
maintaining cell survival-cell death balance [Phospholipidosis]
GRP78 - tumor cell enhanced survlival factor (canonical)[ER stress - tumor survival]
Changing cell homeostasis is a subtype of changing balance: A process that changes the steady state of cell within an organ or an organism.
Any process involved in the maintenance of an internal steady state of cell within an organ or an organism.
Cell homeostasis imbalance is a subtype of homeostasis imbalance: A process that becomes lacking a cell homeostastasis balance.
The process of binding or confining calcium ions such that they are separated from other components of a biological system. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
Dimethyl ester of bilirubin exhibits anti-inflammatory activity through inhibition of secretory phospholipase A2, lipoxygenase and cyclooxygenase.
Secretory phospholipase A2 group IIA modulates insulin sensitivity and metabolism. Secretory phospholipase A2 group IIA (PLA2G2A) is a member of a family of secretory phospholipases that have been implicated in inflammation, atherogenesis, and antibacterial actions. The IIA+ mice were more insulin sensitive and glucose tolerant than the BL/6 mice, even when the IIA+ mice were provided the high fat diet. The IIA+ mice had increased expression of uncoupling protein 1 (UCP1), sirtuin 1 (SIRT1), and PPARγ coactivator 1α (PGC-1α) in brown adipose tissue (BAT), suggesting that PLA2G2A activates mitochondrial uncoupling in BAT.
HMOX1 (predicted)(human)[Phospholipidosis]
Heme oxygenase-1 retards hepatocellular carcinoma progression through the microRNA pathway.
S-Allyl Cysteine Alleviates Hydrogen Peroxide Induced Oxidative Injury and Apoptosis through Upregulation of Akt/Nrf-2/HO-1 Signaling Pathway in HepG2 Cells.
14-3-3ζ inhibits heme oxygenase-1 (HO-1) degradation and promotes hepatocellular carcinoma proliferation: involvement of STAT3 signaling.
PKIB (predicted)(human)[Phospholipidosis]
PKIB promotes cell proliferation and the invasion-metastasis cascade through the PI3K/Akt pathway in NSCLC cells.
KCNMA1 (predicted)(human)[Phospholipidosis]
Combining role with an extracellular signal and transmitting the signal across the membrane by activating an associated G-protein; promotes the exchange of GDP for GTP on the alpha subunit of a heterotrimeric G-protein complex.
A role played by the entity that positively regulates the process ofof G1/S transition of mitotic cell cycle role.
A role played by the entity that positively regulates the process of cell cycle phase transition.
positive regulator of cell cycle phase transition role
Forming a complex of CAD and phospholipid is a subtype of forming a complex of drugs and biological substance: A process that forms a complex consisiting phospholipids and CAD (Cationic Amphiphilic Drug) in the lysosomal membrane, which causes structural change of the membrane. The degree is mild.
forming a complex of CAD and phospholipid (mild)
Forming a complex of CAD and phospholipid is a subtype of forming a complex of drugs and biological substance: A process that forms a complex consisiting phospholipids and CAD (Cationic Amphiphilic Drug) in the lysosomal membrane, which causes structural change of the membrane. The degree is moderate.
forming a complex of CAD and phospholipid (moderate)
Forming a complex of CAD and phospholipid is a subtype of forming a complex of drugs and biological substance: A process that forms a complex consisiting phospholipids and CAD (Cationic Amphiphilic Drug) in the lysosomal membrane, which causes structural change of the membrane. The degree is severe.
forming a complex of CAD and phospholipid (severe)
Any biological process that results in permanent cessation of all vital functions of a cell. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder].
Emerging evidence suggests that mitochondrial dysfunction or maladaptation contributes to detrimental effects on hepatocyte bioenergetics, reactive oxygen species (ROS) homeostasis, endoplasmic reticulum (ER) stress, inflammation, and cell death leading to NASH and HCC.
Glutathione depletion is a subtype of depleting: A process that lessens markedly in the amount of glutathione. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
glutathione depletion [Mitochondrial disorder]
Depletion of mitochondrial GSH levels could also be due to its reduced uptake by mitochondria as a result of enhanced levels of cholesterol within the inner mitochondrial membrane and the decrease in synthesis of S-adenosylmethionine, the major methyl donor in liver and precursor to GSH.
S1P -apoptosis inhibitor[Phospholipidosis - positive regulation of apoptosis]
PLA2positively regulator of immune response (canonical) [Phospholipidosis]
A role played by the entity which positivey regulates the process of infmammatory response.
ASPA (predicted)(human)[Phospholipidosis]
The gene encoding ASPA has been inactivated in the mouse model of CD, and here we show significant decreases in the synthesis of six classes of myelin-associated lipids, as well as reduced acetate levels, in the brains of these mice at the time of peak postnatal CNS myelination. There was an ≈79% reduction in free acetate levels in the brains of ASPA–/– mice but that the levels in kidney and liver were not reduced relative to controls.
Aspartoacylase (ASPA) is a cytosolic zinc metalloenzyme highly expressed in brain white matter, skeletal muscle, kidney, adrenal glands, lung and liver. ASPA catalyses the hydrolysis of N-acetylaspartic acid (NAA) to produce acetate (CH3COO-) and L-aspartate (L-Asp). NAA occurs in high concentration in brain and is thought to play a significant part in the maintenance of intact white matter. In other tissues it acts as a scavenger of NAA from body fluids. Defects in ASPA lead to Canavan disease (CAND; MIM:271900), a fatal neurological disorder of infants characterised by white matter vacuolisation and demyelination (Herga et al. 2006, Le Coq et al. 2006, Bitto et al. 2007).
DAB2 (predicted)(human)[Phospholipidosis]
Dab2 regulates clathrin assembly and cell spreading.
TGFβ stimulation triggers a transient increase in association of Dab2 with Smad2 and Smad3, which is mediated by a direct interaction between the N-terminal phosphotyrosine binding domain of Dab2 and the MH2 domain of Smad2. Dab2 associates with both the type I and type II TGFβ receptors in vivo, suggesting that Dab2 is part of a multiprotein signaling complex. Re-introduction of Dab2 in ovarian, prostate and choriocarcinoma cell lines resulted in a decreased growth rate while Dab2-transfected SKOV3 ovarian carcinoma cells formed tumors 50% smaller compared with parental cells when injected into nude mice, demonstrating that Dab2 acts as a tumor suppressor gene.
Myosin VI and its cargo adaptors - linking endocytosis and autophagy. Owing to the presence of binding motifs for AP-2, clathrin and myosin VI, Dab2 functions as an adaptor that links myosin VI LI to clathrin-mediated receptor endocytosis and degradation.
The clathrin adaptor proteins ARH, Dab2, and numb play distinct roles in Niemann-Pick C1-Like 1 versus low density lipoprotein receptor-mediated cholesterol uptake.
Further, CTSB-mediated Dab2 degradation attenuates drug-induced apoptosis by promoting autophagy and cell survival, and CTSB KD or overexpression of CTSB-resistant Dab2 enhances drug-induced apoptosis by abrogating autophagy. Thus, we identify Dab2 as an inhibitor of autophagy and a promoter of apoptosis, suggesting that targeting of this molecular mechanism may provide therapeutic benefit.
Substance with cytokine role is a subtype of substance with role.
Insulin resistance (process) is a subtype of decreasing sensitivity: A process that changes the sensitivity to the circulating insulin to be lower. This entity is a specific course-dependent process. This process can constitute the course of type II diabetes.
Insulin resistance (process) [Type II Diabetes]
Insulin deficiency is a subtype of malfunctioning process: A process that lacks performing the insulin function required absolutely. This entity is a specific course-dependent process. This process can constitute the course of type I diabetes.
A process that stops, prevents, or reduces the frequency, rate or extent of phospholipid hydrolysis. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (latent).
negative regulation of phospholipid hydrolysis [Phospholipidosis (latent)]
The chemical reactions and pathways resulting in the formation of sphingomyelin, N-acyl-4-sphingenyl-1-O-phosphorylcholine. This entity is a specific course-dependent process. This process can constitute the course of Niemann Pick Disease Type A.
sphingomyelin biosynthetic process[Niemann Pick Disease Type A]
The chemical reactions and pathways resulting in the formation of sphingomyelin, N-acyl-4-sphingenyl-1-O-phosphorylcholine. This entity is a specific course-dependent process. This process can constitute the course of Niemann Pick Disease Type B.
sphingomyelin biosynthetic process[Niemann Pick Disease Type B]
Insulin deficiency is a subtype of malfunctioning process: A process that lacks performing the insulin function required. This entity is a specific course-dependent process. This process can constitute the course of type II diabetes.
insulin relative deficiency [diabetes course]
Hyperfunction of phospholipid degradation (severe) is a subtype of hyperfunction of phospholipid degradation: A process that performs an excessive phospholipid degradation severely.
hyperfunction of phospholipid degradation (severe)
Increasing phospholipid inflow (severe) is a subtype of increase in phospholipid inflow: A process that changes the phospholipid inflow into the hepatocyte to be larger.
The B7 family member B7-H6 is a tumor cell ligand for the activating natural killer cell receptor NKp30 in humans.
NKP30-B7-H6 Interaction Aggravates Hepatocyte Damage through Up-Regulation of Interleukin-32 Expression in Hepatitis B Virus-Related Acute-On-Chronic Liver Failure.
The totality of all processes through which a given Niepamnn-pick disease instance is realized.
EIF2A - cell cycle arresr inducer (canonical)[ER stress - translation]
Cell homeostasis imbalance is a subtype of homeostasis imbalance: A process that becomes lacking a cell homeostastasis balance. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
cell homeostasis imbalance [Phospholipidosis (severe)]
Changing cell homeostasis is a subtype of changing balance: A process that changes the steady state of cell within an organ or an organism. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
changing cell homeostasis [Phospholipidosis]
Any process involved in the maintenance of an internal steady state of cell within an organ or an organism. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
maintaining cell homeostasis [Phospholiipidosis]
Increasing energy is a subtype of increasing quantity: A process that changes the amount of energy to be larger. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
increasing energy [Phospholipidosis(severe)]
Increasing energy is a subtype of increasing quantity: A process that changes the amount of energy to be larger. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
Energy supply is a subtype of providing process to perform a meta-function “to provide energy. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
energy supply [Phospholipidosis(severe)]
Energy supply is a subtype of providing process to perform a meta-function “to provide energy. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
Increasing number of dead cells in liver is a subtype of cell proliferation: A process that becomes larger in the number of dead cells in the liver. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
increasing number of dead cells in liver [Phosholipidosis]
Cell survival-cell death imbalance is a subtype is a subtype of imbalance: A process that lacks a balance between cell death and cell survival within an organ or an organism. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
cell survival-cell death imbalance [Ground glass appearance]
Cell survival-cell death imbalance is a subtype is a subtype of imbalance: A process that lacks a balance between cell death and cell survival within an organ or an organism. This entity is a specific course-dependent process. This process can constitute the course of ER stress.
maintaining cell survival-cell death balance [ER stress]
ceramide -phopholipid metabolite [Phospholipidosis - positive regulation of apoptosis]
Any intermediate or product resulting from phospholipid metabolism.
Decreasing ceramide is a subtype of decreasing lipid: A process that changes the quantity of the ceramide to be lower.
ASAH1 (human) - apoptosis inducer [Phospholipidosis]
Mitochondrial damage dependent molecule is a subtype of toxic course dependent chemical entity. This gene can participate in the course of Mitochondrial damage as a gene product. Gene profile:Human/in vitro/Hepatocyte/
mitochondrial damage dependent molecule (human in vitro)
PBLD (predicted)(human) [mitochondrial damage]
CYP3A5 (predicted)(human) [mitochondrial damage]
TNFSF10 (predicted)(human) [mitochondrial damage]
CXCL6 (predicted)(human) [mitochondrial damage]
RAD51AP1 (predicted)(human) [mitochondrial damage]
Oranic anion export is a subtype of moving A to the outside of B: A process of the directed movement of organic anions into, out of a cell, or an organelle, by means of some agent such as a transporter or pore.
CCL2 (predicted)(human) [mitochondrial damage]
CCL2 is a multifunctional factor involved in various aspects of liver disease pathogenesis, including cirrhosis and hepatocarcinogenesis. Previous studies have shown that CCL2 promotes the accumulation and polarization of macrophages by CCR2 receptor signaling pathway. Our study demonstrated that CCL2 was a critical mediator to link the cytosolic mtDNA stress in HCC cells and TAM infiltration.
CDK1 (predicted)(human) [mitochondrial damage]
Mitochondria-targeted cyclin B1/Cdk1 increases mitochondrial respiration with enhanced oxygen consumption and ATP generation, which provides cells with efficient bioenergy for G2/M transition and shortens overall cell-cycle time.
HMMR (predicted)(human) [mitochondrial damage]
GDF15 (predicted)(human) [mitochondrial damage]
Treatment with alcohol also increased the levels of secreted GDF15 in supernatants of cultured hepatocytes. We next investigated the effect of mitochondrial dysfunction on GDF15 expression in hepatocytes. Inhibition of the mitochondrial OXPHOS complex using oligomycin or rotenone significantly increased Gdf15 expression and GDF15 secretion by cultured hepatocytes. Hepatic Gdf15 expression and serum levels of GDF15 were remarkably increased in alcohol-fed mice.
DHFR (predicted)(human) [mitochondrial damage]
Severe sphingomyelin accumulation in lysosome of nervous system is a subtype of sphingomyelin accumulation in lysosome of nervous system: A process that keeps sphingomyelin in the lysosome of nervous system severely.
severe sphingomyelin accumulation in lysosome of nervous system
Spleen hyperfunction is a subtype of hyperfunctioning: A process that performs an excessive spleen function. This entity is a specific course-dependent process. This process can constitute the course of hepatic blood circulatory disorder.
spleen hyperfunction [hepatic blood circulatory disorder]
Malfunctioning of hepatic blood circulation is a subtype of malfunctioning process: A process that cannot perform hepatic blood circulation function appropriately or cannot realize it at all. This entity is a specific course-dependent process. This process can constitute the course of hepatic blood circulatory disorder.
malfunctioning of hepatic blood circulation [hepatic blood circulatory disorder]
Hepatic vascular circulation disorder dependent process is a subtype of toxic course dependent process: A process that can constitute the course of hepatic vascular circulation disorder.
hepatic vascular circulation disorder dependent process
Hepatic shunt formtion is a subtype of biological structure formation: A process that makes abnormal communications between the hepatic arteries, portal veins, and hepatic or systemic veins. This entity is a specific course-dependent process. This process can constitute the course of hepatic blood circulatory disorder.
hepatic shunt formtion [hepatic blood circulatory disorder]
Inflammatory response is a subtype of changing material: The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
When activated, all three sensors of the unfolded protein response (UPR), PERK, IRE1, and ATF6, participate in upregulating inflammatory processes. ER stress in various cells plays an important role in the pathogenesis of several diseases, including obesity, type 2 diabetes, cancer, and intestinal bowel and airway diseases.
Hepatic fibrosis is a subtype of fibrosis: A process that replaces liver tissues to fibrous connective tissues, usually as a consequence of inflammation or other injury. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
Inflammatory cell infiltration is a subtype of moving A to the inside of B: A process that that moves the outside inflammatory cell to the inside in response to an inflammatory reaction. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
inflammatory cell infiltration [Lipidosis]
Lipid accumulation in hepatocyte is a subtype of lipid storage: A process that keeps lipids in hepatocytes.
Lipid accumulation in hepatocyte (mild) is a subtype of lipid strorage in hepatocyte: A process that keeps lipids in hepatocytes mildly. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
lipid strorage in hepatocyte [Lipidosis (mild)]
lipid accumulation in hepatocyte (mild) [Lipidosis]
An cross-sectional area which is relatively low.
A 2-D extent attribute of the bearer which has been cut off to an axis.
Balooning [Liver PathologicalFindings] is a type of finding observed in the liver. On the basis of pathological morphology, the cytoplasm becomes enlarged like balloons accompanied by the vacuolation.
Balooning [Liver PathologicalFindings] is a type of finding observed in the liver. On the basis of pathological morphology, the cytoplasm becomes enlarged like balloons accompanied by the vacuolation . This finding is observable in the course of lipidosis.
balooning [Liver Pathological Findings] [Lipidosis]
Hypofunction of peroxisomal fatty acid beta-oxidation is a subtype of hypofunction of fatty acid beta-oxidation: A process that performs a decreased or insufficient fatty acid degradation.
hypofunction of peroxisomal fatty acid beta-oxidation
This course is categorized from the viewpoint of the findings of fatty change. This entity is inferred from Description Logic.
A physical quality inhering in a fluid (liquid or gas) by virtue of the amount of fluid which passes through a given surface per unit time.
Mutation is a subtype of changing an operand: A process that changes the nucleotide sequence of DNA randomly and permanently. This entity is a specific course-dependent process. This process can constitute the course of Niemann Pick Disease.
Regulation of transmitting is a subtype of controlling: A process that modulates the frequency, rate or extent of transmitting.
Regulation of bile acid and bile salt transport is a subtype of regulation of transport (biology): Any process that modulates the frequency, rate or extent of the directed movement of bile acid and bile salts .
regulation of bile acid and bile salt transport
A role which enables the directed movement of substances (such as macromolecules, small molecules, ions) into, out of or within a cell, or between cells.
A role enables the energy-independent facilitated diffusion, mediated by passage of a solute through a transmembrane aqueous pore or channel. Stereospecificity is not exhibited but this transport may be specific for a particular molecular species or class of molecules.
Phosphholipid binding by phospholipase is a subtype of phospholipid binding: Interacting selectively and non-covalently with phospholipids byphospholipases.
Protein dimerization is a subtype of protein polymerization: The formation of a protein dimer, a macromolecular structure consists of two noncovalently associated identical or nonidentical subunits.
Niemann–Pick disease dependent process is a subtype of disease course dependent process: A process that can constitute the course of Niemann–Pick disease.
Niemann–Pick disease dependent process [diabetes course]
A role played by the entity that regulates transcriptional elongation by enabling the transition from transcription initiation to elongation or by altering the elongation properties of the enzyme during the elongation phase of transcription.
transcription elongation regulation factor
A role played by the entity to initiate or regulate transcription.
This term is sometimes used for both gene regulatory proteins as well as the general transcription factors.
An early local inflammatory reaction to insult or injury that consists of fever, an increase in inflammatory humoral factors, and an increased synthesis by hepatocytes of a number of proteins or glycoproteins usually found in the plasma.
A role played by the entity which regulates the formation of phospholipids.
A role played by the entity which regulates fatty acid metabolic process.
A role played by the entity which involves in regulating a gene expression process.
Phospholipid metabolism balance is a subtype of maintaining balance: A process that keeps a balance of phospholipid metabolism at small level. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense).
phospholipid metabolism balance [Phospholipidosis (adaptation2)]
Dysfunction of fatty acid degradation is a subtype of dysfunctioning: A process that performs an abnormal and incomplete fatty acid degradation.
A role played by the entity which regulates the glutathione synthesis.
glutathione synthesis regulating agent role
A role played by the entity which enables the facilitated diffusion of a potassium ion (by an energy-independent process) involving passage through a transmembrane aqueous pore or channel without evidence for a carrier-mediated mechanism.
A role played by the entity which enables the facilitated diffusion of a sodium ion (by an energy-independent process) involving passage through a transmembrane aqueous pore or channel without evidence for a carrier-mediated mechanism.
A role played by the entity that brings together two or more molecules through a selective, non-covalent, often stoichiometric interaction, permitting those molecules to function in a coordinated way.
General term for proteins in intracellular signaling pathways that link different proteins in the pathway directly together.
Antipsychotic drugs which can have different modes of action but which tend to be more likely than second generation antipsychotics to cause extrapyramidal motor control disabilities such as body rigidity or Parkinson's disease-type movements; such body movements can become permanent even after treatment has ceased.
Protein that catalyze a specific chemical reaction.
Catalysis role of the reaction: NTP + H2O = NDP + phosphate, to drive the unwinding of a DNA or RNA helix.
Catalysis role of the hydrolysis of various bonds, e.g. C-O, C-N, C-C, phosphoric anhydride bonds, etc. Hydrolase is the systematic name for any enzyme of EC class 3.
Catalysis role of the reaction: ATP + H2O = ADP + phosphate + 2 H+. May or may not be coupled to another reaction.
complex V (mitochondrial electron transport)
A narcotic or opioid substance, synthetic or semisynthetic agent producing profound analgesia, drowsiness, and changes in mood.
Catalysis role of the hydrolysis of any glycosyl bond.
Catalysis role of the removal of damaged bases by cleaving the N-C1' glycosidic bond between the target damaged DNA base and the deoxyribose sugar. The reaction releases a free base and leaves an apurinic/apyrimidinic (AP) site.
Catalysis role of the reaction: GTP + H2O = GDP + phosphate.
A role of the RAS superfamily of GTP (guanosine triphosphate) hydrolysis-coupled signal transduction relay protein. It can be subclassified into RAS, RHO, RAB, and ARF families, as well as the closely related G alpha family. The members of each family can, in turn, be arranged into evolutionarily conserved branches. These groupings reflect structural, biochemical, and functional conservation.
Catalysis role of the reaction: histone N6-acetyl-L-lysine + H2O = histone L-lysine + acetate. This reaction represents the removal of an acetyl group from a histone, a class of proteins complexed to DNA in chromatin and chromosomes.
Catalysis role of the hydrolysis of a glycerophospholipid.
Catalysis role of the hydrolysis of a phosphodiester to give a phosphomonoester and a free hydroxyl group.
Catalysis of the hydrolysis of phosphoric monoesters, releasing inorganic phosphate.
Catalysis role of the reaction: D-glucopyranose 6-phosphate + H2O = D-glucose + phosphate. D-glucopyranose is also known as D-glucose 6-phosphate.
D-glucose-6-phosphate phosphohydrolase activity
glucose 6-phosphate phosphatase activity
Catalysis role of the reaction: a phosphoprotein + H2O = a protein + phosphate. Together with protein kinases, these enzymes control the state of phosphorylation of cell proteins and thereby provide an important mechanism for regulating cellular activity.
Catalysis role of the reaction: protein serine phosphate + H2O = protein serine + phosphate, and protein threonine phosphate + H2O = protein threonine + phosphate.
serine/threonine specific protein phosphatase
Catalysis role of the reactions: protein serine + H2O = protein serine + phosphate; protein threonine phosphate + H2O = protein threonine + phosphate; and protein tyrosine phosphate + H2O = protein tyrosine + phosphate.
Note that this term applies only to free amino acids.
protein serine/threonine/tyrosine phosphatase
Compound accumulation in lysosome is a subtype of accumulation of xenobiotics: A process that keeps compound in the lysosome. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (latent).
compound accumulation in lysosome [Phospholipidosis (latent)]
Catalysis of the reaction: protein tyrosine phosphate + H2O = protein tyrosine + phosphate.
phosphoprotein phosphatase (phosphotyrosine)
protein-tyrosine-phosphate phosphohydrolase
A role played by the entity which enables the transmembrane transfer of an ion by a channel that opens when a specific ligand has been bound by the channel complex or one of its constituent parts.
A role played by the entity interacting selectively and non-covalently and simultaneously with one or more signal transduction molecules, usually acting as a scaffold to bring these molecules into close proximity either using their own SH2/SH3 domains (e.g. Grb2) or those of their target molecules (e.g. SAM68).
This term refers to the adaptor proteins that possesses both SH2 and SH3 domains, such as Grb2, Nck and Crk, and does not include adaptor proteins that contain only SH2 or PTB domains, such as the Shc family and the IRS family.
A role played by the entity interacting selectively and non-covalently and simultaneously with one or more signal transduction molecules, usually acting as a scaffold to bring these molecules into close using Death Domains.
An attribute of morphology inhering in a bearer by virtue of the bearer's physical magnitude.
A role played by the entity that acts as docking sites for multiple signaling molecules.
A role of involving the initiation of ribosome-mediated translation of mRNA into a polypeptide.
Lipid Mediator role is played by a lipid having bioactivity, which is transiently produced locally, acts on a cell membrane receptor located in its place, transmits a signal, and usually is decomposed promptly.
The role of a molecule that contributes to the structural integrity of the ribosome.
A role played by the molecule to mediate adhesion of the cell to the external substrate or to another cell.
The role played by the molecule that contributes to the structural integrity of a cytoskeletal structure.
A role played by the entity that catalyses the generation of force resulting either in movement along a microfilament or microtubule, or in torque resulting in membrane scission, coupled to the hydrolysis of a nucleoside triphosphate.
The role of a molecule that contributes to the structural integrity of a complex or its assembly within or outside a cell.
The role played by the molecule that contributes to the structural integrity of an microfilament (actin filament). Actin filaments are a major component of the contractile apparatus of skeletal muscle and the microfilaments of the cytoskeleton of eukaryotic cells
The role played by the molecule that contributes to the structural integrity of the intermediate filaments.
The role played by the molecule that contributes to the structural integrity of cytoskeletal fibers.
The role of a molecule that contributes to the structural integrity of the extracellular matrix.
extracellular matrix structural constituent
A role played by the entity of transport systems. This type enable facilitated diffusion of water (by an energy-independent process) by passage through a transmembrane aqueous pore or channel without evidence for a carrier-mediated mechanism.
A role played by the entity which enables the transfer of amino acids from one side of a membrane to the other. Amino acids are organic molecules that contain an amino group and a carboxyl group.
A role played by the entity which enables the transfer of a substance, usually a specific substance or a group of related substances, from one side of a membrane to the other.
A role played by the entity which enables the directed movement of lipids into, out of or within a cell, or between cells.
A role played by the entity which enables the directed movement of phospholipids into, out of or within a cell, or between cells. Phospholipids are a class of lipids containing phosphoric acid as a mono- or diester.
A role played by the entity which enables the transfer of a sugar from one side of a membrane to the other. A sugar is any member of a class of sweet, water-soluble, crystallizable carbohydrates, which are the monosaccharides and smaller oligosaccharides.
A role played by the entity which enables the transfer of an ion from one side of a membrane to the other up the solute's concentration gradient. This is carried out by binding the solute and undergoing a series of conformational changes. Transport works equally well in either direction.
A role played by the entity which enables the transfer of bile acid from one side of a membrane to the other. Bile acids are any of a group of steroid carboxylic acids occurring in bile, where they are present as the sodium salts of their amides with glycine or taurine.
Transport (influx) of bile salts and acids by OATP-A, Homo sapiens
Transport (influx) of glycocholate and taurocholate by OATP-C, Homo sapiens
Transport (influx) of glycocholate and taurocholate by OATP-8, Homo sapiens
A role played by the entity which enables the transfer of a solute or solutes from one side of a membrane to the other according to the reaction: bile acid(out) + Na+(out) = bile acid(in) + Na+(in).
A role played by the entity which changes the size of the operand(s).
The entity of the alpha, beta, and gamma subunits (or beta-gamma dimers) of heterotrimeric guanine nucleotide binding (G) proteins. It is an intracellular membrane-associated protein activated by various receptors (e.g., beta adrenergic). It serves as transducers of the receptor-initiated response linked to intracellular elements, such as enzymes, that generate second messengers to initiate an effect.
A role played by the entity which changes the quality of the operand(s).
A role played by the entity to make multiple components to an assembly
A role played by the entity that inhibits molecular activity.
A role played by the entity involved in changing process.
A role played by the entity which regulates molecular activities.
A role played by the entity that activates molecular activity.
type converter is a role played by the entity to change the type of the operand(s)
A role played by the entity that interacts specifically and non-covalently with a DNA-bound DNA-binding transcription factor to either activate or repress the transcription of specific genes. Coregulators often act by altering chromatin structure and modifications. For example, one class of transcription coregulators modifies chromatin structure through covalent modification of histones. A second ATP-dependent class modifies the conformation of chromatin. A third class modulates interactions of DNA-binding transcription factor with other transcription coregulators.
A role played by the entity that interacts specifically and non-covalently with a DNA-bound DNA-binding transcription factor to activate the transcription of specific genes. Coactivators often act by altering chromatin structure and modifications. For example, one class of transcription coregulators modifies chromatin structure through covalent modification of histones. A second ATP-dependent class modifies the conformation of chromatin. Another type of coregulator activity is the bridging of a DNA-binding transcription factor to the basal transcription machinery. The Mediator complex, which bridges transcription factors and RNA polymerase, is also a transcription coactivator.
A role of the entity which positively/negatively regulates a signaling pathway or metabolic pathway.
negative regulator of Wnt signaling pathway
A role played by the entity which binds to and modulates the activity of an enzyme.
A role of the entity of binding to a specific ion or molecule and delivering it either to an acceptor molecule or to a specific location.
A role played by the entity which positively regulates the process of tumorigenesis.
positive regulator of tumorigenesis role
A role played by the entity that regulates the activity of tumor cells.
A role played by the entity which regulates the process of infmammatory response.
A role played by the entity of funtion as realizable entity.
A physical attribute inhering in a bearer by virtue of the bearer's resistance to pressure, being broken, or pierced
A role played by the entity involved in changing some state.
A role played by the entity that contributes to keep the structural integrity.
A role played by the entity which assists the molecule activity.
Keeping structure is a subtype of changing structure: A process that maintains the structure of the object at a constant level .
GRP94 - tumor cell enhanced survlival factor (canonical)[ER stress]
HSP90B1 - tumor cell production promoting factor (human)[ER stress]
Endoplasmic reticulum heat shock protein gp96 maintains liver homeostasis and promotes hepatocellular carcinogenesis. Inhibition of gp96 in human HCCs perturbed multiple growth signals, and attenuated proliferation and expansion.
ER stress dependent process (molecular level) is a subtype of ER stress dependent process: A process that can constitute the course of endoplasmic reticulum stress and specifies the molecular level.
ER stress dependent process (molecular level)
The aggregation, arrangement and bonding together of the apoptosome, a multisubunit protein complex involved in the signaling phase of the apoptotic process. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
Leaking content from cell is a subtype of leaking: A process that leaks contents from the cell. This entity is a specific course-dependent process. This process can constitute the course of Cholestasis.
Inflammatory cell infiltration is a subtype of moving A to the inside of B: A process that that moves the outside inflammatory cell to the inside in response to an inflammatory reaction. This entity is a specific course dependent process. This process can constitute the course of Cholestasis.
inflammatory cell infiltration [Cholestasis]
Increasing organelle volume is a subtype of increasing volume: A process that changes the volume of the organelle to be higher.
Hepatic fibrosis dependent process is a subtype of toxic course dependent process: A process that can constitute the course of hepatic fibrosis.
Kupffer cell activation is a subtype of macrophage activation: A change in morphology and behavior of a kupffer cell resulting from exposure to a cytokine, chemokine, cellular ligand, or soluble factor. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
It is an attribute of structure inhering in a bearer by virtue of the bearer's disposition to being permeated or pervaded by a gas or liquid (as by osmosis or diffusion).
The regulated release of cytokines from a cell. Cytokines are any of a group of proteins that function to control the survival, growth and differentiation of tissues and cells, and which have autocrine and paracrine activity. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
A change in the morphology or behavior of a hepatic stellate cell resulting from exposure to a cytokine, chemokine, hormone, cellular ligand or soluble factor. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
hepatic stellate cell activation [Fibrosis]
A physical attribute inhering in a fluid (liquid or gas) by virtue of the amount of fluid which passes through a given surface per unit time.
Hepatic fibrosis dependent chemical entity is a subtype of toxic course dependent chemical entity. This entity can participate in the course of hepatic fibrosis.
hepatic fibrosis dependent chemical entity
Hepatic fibrosis dependent gene is a subtype of toxic course dependent chemical entity. This gene can participate in the course of hepatic fibrosis as a gene product. Gene profile:caonical that described in textbooks or articles.
hepatic fibrosis dependent molecule (canonical)
Counting numbers of objects and how many times an event happens are essential not to individuals in them but to collectives of objects or events.
Addition of xenobiotics is a subtype of addition of foreign substance: A process that xenobiotics to make an addition to a cell, organelle, or an organism.
The multiplication or reproduction of hepatic stellate cells, resulting in the expansion of a hepatic stellate cell population. Hepatic stellate cells are found in the perisinusoidal space of the liver, and are capable of multiple roles including storage of retinol, presentation of antigen to T cells (including CD1d-restricted NKT cells), and upon activation, production of extracellular matrix components. This cell type comprises approximately 8-15% of total cells in the liver. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
hepatic stellate cell proliferation [Fibrosis]
Increasing drug metabolite is a subtype of increasing quantity: A process that changes the amount of drug metabolites to be higher. This entity is a specific course-dependent process. This process can constitute the course of lipidosis.
The process in which a relatively unspecialized cell acquires specialized features of a myoblast. A myoblast is a mononucleate cell type that, by fusion with other myoblasts, gives rise to the myotubes that eventually develop into striated muscle fibers. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
A number quality which is relatively few.
A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of structures in the space external to the outermost structure of a cell. For cells without external protective or external encapsulating structures this refers to space outside of the plasma membrane, and also covers the host cell environment outside an intracellular parasite. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
extracellular structure organization [Fibrosis]
This gene encodes a cysteine-rich cationic antimicrobial peptide that is expressed predominantly in the liver. The mature peptide has activity against gram-positive bacteria and yeasts. [provided by RefSeq, Sep 2014]
These findings suggest a model in which LEAP2 could act at the extracellular level as a modulator of FGF and activin signals in relation with cellular processes such as cell differentiation and migration.
Any process that decreases the rate, frequency or extent of extracellular matrix disassembly. Extracellular matrix disassembly is a process that results in the breakdown of the extracellular matrix. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
negative regulation of extracellular matrix disassembly [Fibrosis]
This gene encodes a chromatin-associated protein involved in the regulation of gene transcription, integration of retroviruses into chromosomes, and the metastatic progression of cancer cells. The encoded protein preferentially binds to the minor groove of AT-rich regions in double-stranded DNA. Multiple transcript variants encoding different isoforms have been found for this gene. Pseudogenes of this gene have been identified on multiple chromosomes. [provided by RefSeq, Jan 2016]
The High Mobility Group A1 (HMGA1) gene is highly overexpressed in human uterine serous carcinomas and carcinosarcomas and drives Matrix Metalloproteinase-2 (MMP-2) in a subset of tumors.
HMGA1 Expression in Human Hepatocellular Carcinoma Correlates with Poor Prognosis and Promotes Tumor Growth and Migration in in vitro Models. HMGA1 is frequently expressed in cirrhotic tissues and HCCs and its expression is associated with worse prognosis in HCC.
This course is categorized from the viewpoint of pathological findings derived by inference.
toxic course based on pathological findings
This course is categorized from the viewpoint of the findings of eosinogranular degeneration.
toxic course based on the eosinogranular degeneration (finding)
This course is categorized from the viewpoint of the findings of ground glass appearance.
toxic course based on ground glass appearance
CERB processing is a subtype of protein processing: CREB maturation process achieved by the cleavage of a peptide bond or bonds within CREB protein.
The chemical reactions resulting in the breakdown of misfolded proteins in the cytoplasm, which are targeted to cytoplasmic proteasomes for degradation.
cytoplasm-associated proteasomal ubiquitin-dependent protein catabolism
cytoplasm-associated proteasomal ubiquitin-dependent protein degradation
See also the biological process terms 'unfolded protein response ; GO:0030968' and 'retrograde protein transport, ER to cytosol ; GO:0030970'.
cytoplasm protein quality control by the ubiquitin-proteasome system
Hepatic fibrosis dependent chemical compound is a subtype of toxic course dependent chemical entity. This entity (drug) can participate in the course of hepatic fibrosis.
hepatic fibrosis dependent chemical compound
A type of cell death that is morphologically characterized by an increasingly translucent cytoplasm, swelling of organelles, minor ultrastructural modifications of the nucleus (specifically, dilatation of the nuclear membrane and condensation of chromatin into small, irregular, circumscribed patches) and increased cell volume (oncosis), culminating in the disruption of the plasma membrane and subsequent loss of intracellular contents. Necrotic cells do not fragment into discrete corpses as their apoptotic counterparts do. Moreover, their nuclei remain intact and can aggregate and accumulate in necrotic tissues. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
CCL3 production is a subtype of generating a substance : A process that synthesizes trichloromethyl(.) as output.
Decreasing blood flow is a subtype of decreasing flow: A process that changes the blood flow to be smaller. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
Scarring is a subtype of changing material: A process of keeping area replaced into fibrous tissue by injury. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
The process in which the anatomical structures of the nodule are generated and organized. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
negative regulation of apoptotic process [Fibrosis]
CCL3 production is a subtype of generating a substance : A process that synthesizes trichloromethyl(.) as output. This entity is a specific course-dependent process. This process can constitute the course of NASH.
CCl4 is activated by cytochrome (CYP)2E1, CYP2B1 or CYP2B2, and possibly CYP3A, to form the trichloromethyl radical, CCl3*.
CTSB (predicted)(human)[Phospholipidosis]
Lysosomal cysteine protease, cathepsin B, is targeted to lysosomes by the mannose 6-phosphate-independent pathway in rat hepatocytes: site-specific phosphorylation in oligosaccharides of the proregion.
These observations suggest that the mechanism of insertion of cathepsin B on the plasma membrane and its cellular traffic can be dependent on heparan sulfate proteoglycans present at cell surface. In addition, this hypothesis is also supported by the perinuclear cathepsin B location in tumor cells, as also observed for the cellular distribution of heparan sulfate complexed to fibroblast growth factor.
Treatment of the double-chain form of cathepsin B from normal liver and tumours with the endoglycosidase peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase converted the 26 kDa form into 25 kDa in SDS/polyacrylamide gels, suggesting that cathepsin B may exist as both glycosylated and unglycosylated forms. Our results, in contrast with those reported earlier for mouse cathepsin B, indicate that human liver and tumour cathepsin B are similar.
Lysosomal hydrolases of different classes are abnormally distributed in brains of patients with Alzheimer disease.
Cathepsin-B-mediated cleavage of Disabled-2 regulates TGF-β-induced autophagy. CTSB-mediated degradation of Dab2 allows Beclin-1-Vps34 induction of autophagy, whereas sustained Dab2 expression prevents autophagy and promotes apoptosis by stabilizing the pro-apoptotic Bim protein. In vivo studies suggest that Dab2-mediated regulation of autophagy modulates chemotherapeutic resistance and tumour metastasis.
Decreasing stored glycogen is a subtype of decreasing glycogen level: A process that changes the stored amount of glycogen level to be lower.
Any process that stops, prevents or reduces the frequency, rate or extent of gap junction assembly. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
negative regulation of gap junction assembly [Ground glass appearance]
During cell division, cell-cell communication through gap-junctions is temporarily disrupted. Tumor promotors such as phenobarbital decrease gap junctional intercellular communication. Casarett & Doull's Toxicology: The Basic Science of Poisons, Eighth Edition
CAR (canonical)[Ground glass appearance]
The process resulting in division and partitioning of components of a cell to form more cells. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
Prevention of degradation of mRNA molecules. In the absence of compensating changes in other processes, the slowing of mRNA degradation can result in an overall increase in the population of active mRNA molecules.
Any process that activates or increases the frequency, rate or extent of cell division. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
positive regulation of cell division [Ground glass appearance]
Negative regulation of adherens junction assembly is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of adherens junction assembly. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
negative regulation of adherens junction assembly [Ground glass appearance]
Changing cycle phase is a subtype of changing quality: A process that changes the cycle phase.
Maintaining cyclicity is a subtype of changing cyclicity: A process that keepss the repeating values in regular cycles (periods).
Cytochrome P450 activation is a subtype of molecular activation: A process that changes the activity of the cytochrome P450 to be higher. This entity is a specific course-dependent process. This process can constitute the course of NASH.
Extracellular matrix production- degradation imbalance is a subtype of imbalance: A process that lacks a balance between extracellular matrix production and degradation. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
extracellular matrix production- degradation imbalance [Fibrosis]
Extracellular matrix production- degradation imbalance is a subtype of imbalance: A process that lacks a balance between extracellular matrix production and degradation.
extracellular matrix production- degradation imbalance
Hepatic fibrosis is a subtype of fibrosis: A process that replaces liver tissues to fibrous connective tissues, usually as a consequence of inflammation or other injury. This entity is a specific course-dependent process. This process can constitute the course of Fibrosis.
The totality of all processes through which hepatic fibrosis is realized by alcoholic liver injury.
hepatic fibrosis by alcoholic liver injury
The totality of all processes through which hepatic fibrosis is realized by NASH.
CYP1A2(canonical) [Glutathione depletion]
The critically reactive metabolite of AFB1 is the exo 8,9-epoxide formed by a two-electron oxidation mainly catalyzed by CYP3A4, with contribution from CYP1A2 and other CYPs.
Overeating is a subtype of increasing quantity: A process that changes the ingestion amount of food to be larger. This entity is a specific course-dependent process. This process can constitute the course of NAFLD.
Increasing fatty acid synthesis substrate is a subtype of increasing quantity: A process that changes the production amount of the substrate of the fatty acid synthesis. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
increasing fatty acid synthesis substrate [lipidosis]
Converting to acetyl CoA is a subtype of metabolic process. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis (NAFLD).
Increasing amount of carbohydrate is a subtype of increasing quantity: A process that changes the amount of carbohydrates to be higher. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis (NAFLD).
increasing amount of carbohydrate [NAFLD]
Increase in lipid inflow into hepatocyte is a subtype of increasing quantity: A process that changes the lipid inflow into the hepatocyte to be larger. This entity is a specific course-dependent process. This process can constitute the course of NAFLD.
increase in lipid inflow into hepatocyte [NAFLD]
Increaing in fatty acid inflow into hepatocyte is a subtype of increasing quantity: A process that changes the fatty acid inflow into the hepatocyte to be larger. This entity is a specific course-dependent process. This process can constitute the course of NAFLD.
increaing in fatty acid inflow into hepatocyte [NAFLD]
Negative regulation of adherens junction assembly is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of adherens junction assembly.
negative regulation of adherens junction assembly
A role played by the entity to transmit something to be detected.
Molecular assembly is a subtype of assembling: The aggregation, arrangement and bonding together of molecules.
A role played by the entity to transmit the stress to be detected.
tunicamycin - apoptosis inducer [ER stress]
tunicamycin - lipidosis inducer [ER stress]
Melanin granule is a sutype of pigment granule
A role played by the entity which involves in inducing lipidosis
Lysosomal cholesterol storage is a subtype of cholesterol storage: A process that keeps cholesterol in the lysosome severely. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
lysosomal cholesterol storage (severe)[Phospholipidosis]
Inflammasome activation is a subtype of activating: A process that changes the activity of the inflammasome to be higher. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
Inflammatory cytokine gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature inflammatory cytokine gene product or products (proteins or RNA). This entity is a specific course-dependent process. This process can constitute the course of Cell death.
Inflammatory cytokine gene expression[pyroptosis]
Compound accumulation in liver is a subtype of accumulation of xenobiotics: A process that keeps compound in the liver. This entity is a specific course-dependent process. This process can constitute the course of Cell death.
compound accumulation in liver [Cell death]
Inflammatory response is a subtype of changing material: The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages. This entity is a specific course-dependent process. This process can constitute the course of pyroptosis.
Inflammatory cell infiltration is a subtype of moving A to the inside of B: A process that that moves the outside inflammatory cell to the inside in response to an inflammatory reaction. This entity is a specific course-dependent process. This process can constitute the course of pyroptosis.
inflammatory cell infiltration [pyroptosis]
Hyperfunction of phenobarbital metabolism phase I by Cytochrome P450 is a subtype of hyperfunction of drug metabolism phase I: A process that performs an excesssive phenobarbital metabolism phase I by Cytochrome P450. This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (sustained) .
hyperfunction of phenobarbital metabolism phase I by Cytochrome P450 (sustained) [Ground glass appearance]
Smooth endoplasmic reticulum membrane organization is a subtype of endoplasmic reticulum membrane organization: A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts of a smooth endoplasmic reticulum membrane. This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (sustained) .
smooth endoplasmic reticulum membrane organization (sustained) [Ground glass appearance]
Hyperfunction of drug metabolism phase I is a subtype of hyperfunction of drug metabolism: A process that performs an excesssive drug metabolism phase I. This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (sustained) .
hyperfunction of drug metabolism phase I (sustained) [Ground glass appearance]
Hyperfunction of decreasing the amount of phenobarbital is a subtype of hyperfunction of decreasing: A process that performs an excesssive decreasing the amount of the phenobarbital. This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (sustained) .
hyperfunction of decreasing the amount of phenobarbital (sustained) [Ground glass appearance]
Hyperfunction of glucuronic acid conjugation is a subtype of hyperfunction of drug metabolism phase II: A process that performs an excessive glucuronic acid conjugation. This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (sustained) .
hyperfunction of glucuronic acid conjugation for phenobarbital intermediate metabolite (sustained) [Ground glass appearance]
Hyperfunction of drug metabolism phase II is a subtype of hyperfunction of drug metabolism: A process that performs an excessive drug metabolism phase II. This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (sustained) .
hyperfunction of drug metabolism phase II (sustained) [Ground glass appearance]
The chemical reaction resulting in the formation of reactive oxygen species, any molecules or ions formed by the incomplete one-electron reduction of oxygen. This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (sustained) .
reactive oxygen species biosynthetic process (sustained) [Ground glass appearance]
Mitochondrial dysfunction is a subtype of dysfunctioning: A process that performs an abnormal and incomplete mitochondrial function. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
mitochondrial dysfunction [Ground glass appearance]
A type of cell death that is morphologically characterized by an increasingly translucent cytoplasm, swelling of organelles, minor ultrastructural modifications of the nucleus (specifically, dilatation of the nuclear membrane and condensation of chromatin into small, irregular, circumscribed patches) and increased cell volume (oncosis), culminating in the disruption of the plasma membrane and subsequent loss of intracellular contents. Necrotic cells do not fragment into discrete corpses as their apoptotic counterparts do. Moreover, their nuclei remain intact and can aggregate and accumulate in necrotic tissues. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
The chemical reactions and pathways resulting in the breakdown of glycogen, a polydisperse, highly branched glucan composed of chains of D-glucose residues. This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (sustained) .
glycogen catabolic process (sustained) [Ground glass appearance]
Activation of the constitutive androstane receptor inhibits gluconeogenesis without affecting lipogenesis or fatty acid synthesis in human hepatocytes.
Making existence of drug is a subtype of making existence of xenobiotics: A process that makes a drug to be present in in a cell, organelle, or an organism.
Nuclear receptor activation is a subtype of activation of transcription factor: A process that changes the activity of the molecule with a nuclear receptor role to be higher. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
activating nuclear receptor [Ground glass appearance]
nuclear receptor activating [Ground glass ]
nuclear receptor activation [Ground glass appearance]
Phenobarbital metabolism imbalance is a subtype of imbalance: A process that becomes lacking a homeostastasis balance of the phenobarbital metabolism. And the degree is severe. This process is dependent on the tumorigenesis and can constitute the course of Ground glass appearance (severe).
phenobarbital metabolism imbalance [Ground glass appearance (severe) - tumorigenesis]
The totality of all processes through which ground glass appearance is realized. This toxic course has processes of CYP activation.
ground glass appearance with Cytochrome P450 activation [toxic course]
Hyperfunction of cytochrome p450 gene expression by phenobarbital is a subtype of hyperfunction of drug metabolizing enzyme gene expression: A process that performs an excesssive gene expression of cytochrome p450 by phenobarbital. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
CAR activator phenobarbital can induce CYP2B10 and CYP3A11 in wild type and PXR knock-out mouse.
hyperfunction of cytochrome p450 gene expression by phenobarbital [Ground glass appearance]
Humans have a single CYP2B gene, CYP2B6; whereas mice have five Cyp2b genes, Cyp2b9, Cyp2b10, Cyp2b13, Cyp2b19, and Cyp2b23 (Nelson et al., 2004). In mice, Cyp2b9, Cyp2b10, and Cyp2b13 are the forms primarily expressed in the liver (Finger et al., 2011). Cyp2b10 is transcriptionally regulated by CAR (Honkakoski et al., 1998; Zhang et al., 2002; Wang et al., 2003; Kretschmer and Baldwin, 2005) and it is highly inducible by PB treatment (Honkakoski et al., 1998; Li-Masters and Morgan, 2001).
Hyperfunction of decreasing the amount of drugs is a subtype of hyperfunction of decreasing: A process that performs an excesssive decreasing the amount of drugs. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
hyperfunction of decreasing the amount of drugs [Ground glass appearance]
Phenobarbital metabolism imbalance is a subtype of imbalance: A process that becomes lacking a homeostastasis balance of the phenobarbital metabolism. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
phenobarbital metabolism imbalance [Ground glass appearance]
Hyperfunction of decreasing the amount of drugs is a process of performing an excessive function of decreasing the amount of drugs by Cytochrome P450. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
hyperfunction of decreasing the amount of drugs by Cytochrome P450 [Ground glass appearance]
A role played by the entity which receives xenobiotics (signal) and transmits operand(s).
Hyperfunction of phenobarbital metabolism phase I by Cytochrome P450 is a subtype of hyperfunction of drug metabolism phase I: A process that performs an excesssive that performs an excesssive phenobarbital metabolism phase I by Cytochrome P450. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
hyperfunction of phenobarbital metabolism phase I by Cytochrome P450 [Ground glass appearance]
Any process that modulates the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of precursor metabolites, substances from which energy is derived, and the processes involved in the liberation of energy from these substances. This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (sustained) .
regulation of generation of precursor metabolites and energy (sustained) [Ground glass appearance]
The totality of all processes through which ground glass appearance is realized. This toxic course has a process of CYP activation by phenobarbital and manifests liver tumor.
phenobarbital induced liver tumor via ground glass appearance
Long-term treatment with CAR activators such as TCPOBOP and Phenobarbitone results in a strain- and species-specific induction of liver tumors in rats and mice.(Diwan et al. 1992). It is due to the stimulation of S-phase DNA synthesis leading to hepatocyte proliferation and a decrease in apoptosis (Hasmall and Roberts 1999). This process appears morphologically as a temporal progression from centrilobular hepatocyte hypertrophy (with a concomitant induction of Cyp2b enzymes) , and ultimately the appearance of adenomas and carcinomas (Ross et al. 2010).
Clonal expansion of preneoplastic cell is a subtype of clonal expansion: A process that becomes larger in the number of preneoplastic cells by cell division of a population of identical cells descended from a single progenitor.
Hyperfunction of increasing the amount of drug is a process of performing an excessive function of increasing the amount of drugs. And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (moderate) .
hyperfunction of increasing the amount of phenobarbital [Ground glass appearance (moderate) ]
Phenobarbital metabolism imbalance is a subtype of imbalance: A process that becomes lacking a homeostastasis balance of the phenobarbital metabolism. And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (moderate) .
phenobarbital metabolism imbalance [Ground glass appearance (moderate) ]
Phenobarbital accumulation in liver is a subtype of compound accumulation in liver: A process that keeps phenobarbital in the liver. And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (moderate) .
phenobarbital accumulation in liver [Ground glass appearance (moderate) ]
Hyperfunction of decreasing the amount of phenobarbital is a subtype of hyperfunction of decreasing: A process that performs an excesssive decreasing the amount of the phenobarbital. And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (moderate) .
hyperfunction of decreasing the amount of phenobarbital [Ground glass appearance (moderate) ]
Hyperfunction of glucuronic acid conjugation is a subtype of hyperfunction of drug metabolism phase II: A process that performs an excessive glucuronic acid conjugation. And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (moderate) .
hyperfunction of glucuronic acid conjugation for phenobarbital intermediate metabolite [Ground glass appearance (moderate) ]
Hyperfunction of phenobarbital metabolism phase I by Cytochrome P450 is a subtype of hyperfunction of drug metabolism phase I: A process that performs an excesssive phenobarbital metabolism phase I by Cytochrome P450. And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (moderate) .
hyperfunction of phenobarbital metabolism phase I by Cytochrome P450 [Ground glass appearance (moderate) ]
Hyperfunction of cytochrome p450 gene expression is a subtype of hyperfunction of drug metabolizing enzyme gene expression: A process that performs an excesssive gene expression of cytochrome p450. And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (moderate) .
hyperfunction of cytochrome p450 gene expression by phenobarbital [Ground glass appearance (moderate) ]
Constitutive androstane receptor activation by phenobarbital is a subtype of activating nuclear receptor: A process that changes the activity of the activating CAR ( constitutive androstane receptor) with a nuclear receptor role to be higher by phenobarbital. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (moderate) .
CAR activating [sustained] [Ground glass ]
constitutive androstane receptor activation by phenobarbital (moderate) [Ground glass appearance ]
A process that performs an excesssive moving the phenobarbital to the inside of liver. And the degree is moderate. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (moderate) .
hyperfunction of moving phenobarbital to the inside of liver [Ground glass appearance (moderate) ]
Any process that activates, maintains or increases the rate of autophagy. Autophagy is the process in which cells digest parts of their own cytoplasm. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis
positive regulation of autophagy [Phospholipidosis]
CTSB- autophagy inducing factor (human)[Phospholipidosis - autophagy indution]
CTSB- tumor cell metastasis factor (human)[Phospholipidosis - tumor metasitasis]
These observations suggest that the mechanism of insertion of cathepsin B on the plasma membrane and its cellular traffic can be dependent on heparan sulfate proteoglycans present at cell surface. In addition, this hypothesis is also supported by the perinuclear cathepsin B location in tumor cells, as also observed for the cellular distribution of heparan sulfate complexed to fibroblast growth factor. It has been shown that lysosomal cysteine proteinases, specially cathepsin B, can participate in tumor invasion by degradation of extracellular matrix components. This can take place either intracellularly by heterophagosomal activity of tumors cell or extracellularly by cell surface associated cathepsin B . It has been demonstrated that the presence of cathepsin B at plasma membrane results in focal dissolution of extracellular matrix proteins and enables the tumor cell to invade.
A role played by the entity which positively regulates the tumor metastasis.
CYP4A11 - arachidonic acid metabolic factor (human)[Phospholipidosis]
Negative regulation of arachidonic acid metabolic process is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of the arachidonic acid metabolism.
negative regulation of arachidonic acid metabolic process
Hyperfunctioning of apoptotic process is a subtype of hyperfunctioning: A process that performs an excesssive autophagy.
The chemical reactions and pathways involving arachidonic acid, a straight chain fatty acid with 20 carbon atoms and four double bonds per molecule. Arachidonic acid is the all-Z-(5,8,11,14)-isomer.
The chemical reactions and pathways by which arachidonic acid is converted to other compounds initially by omega-hydroxylation.
Negative regulation of arachidonic acid metabolic process is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of the arachidonic acid metabolism. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
negative regulation of arachidonic acid metabolic process [phospholipidosis]
A role played by the entity which inhibits the tumor progression.
Hyperfunctioning of apoptotic process is a subtype of hyperfunctioning: A process that performs an excesssive apoptosis. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense) .
Hyperfunctioning of apoptotic process [Phospholipidosis (excessive defense) ]
TGFbeta signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the cytokine TGFbeta. This process is dependent on the apoptosis inhibition and can constitute the course of Phospholipidosis (excessive defense) .
TGF beta receptor signaling (primitive) [Phospholipidosis (excessive defense) - apoptosis inhibition ]
TGFbeta (canonical)[Phospholipidosis - apotosis inhibitor]
Here we report the identification and characterization of a novel FNIP1 homolog FNIP2 that also interacts with FLCN and AMPK. FNIP2 expression was higher relative to FNIP1 in fat, liver and pancreas, which may suggest that FNIP2 has a specific function in those metabolic tissues.
We identify FLCN and its binding partners, FNIP1/2, as Rag-interacting proteins with GAP activity for RagC/D, but not RagA/B. Thus, we reveal a role for RagC/D in mTORC1 activation and a molecular function for the FLCN tumor suppressor. FLCN-GFP was found diffusely throughout the cell when FNIP2 was not co-expressed, suggesting that FNIP2 is required for the lysosomal localization of FLCN.
A mutation in the canine gene encoding folliculin-interacting protein 2 (FNIP2) associated with a unique disruption in spinal cord myelination.
Starvation evokes FLCN recruitment to lysosomes, and FNIP co-expression facilitates the FLCN accumulation at the lysosomal membrane through the formation of the FLCN complex. Degradation of FNIP2 leads to lysosomal dissociation of FLCN and subsequent lysosomal association of mTOR, which in turn promotes the proliferation of renal cancer cells. These results indicate that SCFβ-TRCP negatively regulates the FLCN complex by promoting FNIP degradation and provide molecular insight into the pathogenesis of BHD-associated renal cancer.
TGFB1(canonical)[Phospholipidosis - apotosis inhibitor]
Tgfb1(mouse)[Phospholipidosis - apotosis inhibitor]
Degradation of Dab2 is a subtype of protein catabolic process: A process of the chemical reactions resulting in the breakdown of Dab2.
Degradation of Dab2 is a subtype of protein catabolic process: A process of the chemical reactions resulting in the breakdown of Dab2. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
Smooth endoplasmic reticulum proliferation in hepatocyte is a subtype of endoplasmic reticulum proliferation in hepatocyte: A process that becomes larger in the number of smooth endoplasmic reticulum in hepatocyte(s). This process is dependent on the Cyp activation and can constitute the course of Ground glass appearance.
smooth endoplasmic reticulum proliferation in hepatocyte [Ground glass appearance - Cyp]
Hyperfunction of drug metabolism phase II is a subtype of hyperfunction of drug metabolism: A process that performs an excessive drug metabolism phase II. This process is dependent on the CYP activation and can constitute the course of Ground glass appearance.
hyperfunction of drug metabolism phase II [Ground glass appearance - Cyp]
Smooth endoplasmic reticulum proliferation in hepatocyte is a subtype of endoplasmic reticulum proliferation in hepatocyte: A process that becomes larger in the number of smooth endoplasmic reticulum in hepatocyte(s). This process is dependent on the phenobarbital induced CYP activation and can constitute the course of Ground glass appearance.
smooth endoplasmic reticulum proliferation in hepatocyte [Ground glass appearance - Cyp - PB]
Clonal expansion of preneoplastic cell is a subtype of clonal expansion: A process that becomes larger in the number of preneoplastic cells by cell division of a population of identical cells descended from a single progenitor. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
Inhibition of apoptosis by phenobarbital promotes clonal expansion of preneoplastic cells.
clonal expansion of preneoplastic cell [Ground glass appearance]
Any process that stops, prevents, or reduces the frequency, rate or extent of epidermal growth factor receptor signaling pathway activity. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
negative regulation of epidermal growth factor receptor signaling pathway [Ground glass appearance]
Phenobarbital Indirectly Activates the Constitutive Active Androstane Receptor (CAR) by Inhibition of Epidermal Growth Factor Receptor Signaling Phenobarbital bound to EGFR and potently inhibited the binding of EGF, which prevented the activation of EGFR. This abrogation of EGFR signaling induced the dephosphorylation of RACK1 which then promoted the dephosphorylation of CAR by the catalytic core subunit of protein phosphatase 2A.
EGF stimulates homodimerization, retaining CAR in its phosphorylated (i.e., inactivated) form, while CAR activators antagonize EGF to dissociate the homodimer for activation.
phenobarbital -EGFR signalling inhibitor [Ground glass appearance]
Cyp2b10 (mouse)[Ground glass appearance]
A typical effect of CAR activation by PB is a marked induction of Cyp2b10 expression in the liver; PB induces hepatic Cyp2b10 expression and hepatocyte proliferation to greater extents in male mice than in female mice. In male mice, CYP2B plays a significant, but partial, role in PB-induced hepatocyte proliferation.
Cyp3a11 (mouse)[Ground glass appearance]
Phenobarbital can maximally induce CYP2B10 and CYP3A11 in wild-type and PXR knockout moice, indicating that CAR also can induce both CYP2B and CyP3A enzymes. Casarett & Doull's Toxicology: The Basic Science of Poisons, Eighth Edition
6-(4-chlorophenyl)imidazo(2,1-b)(1,3)thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime [Ground glass appearance]
CITCO and phenytoin as selective hCAR activators
A role of the entity which negatively regulates the EGFR signaling pathway.
EGFR (canonical)[Ground glass appearance]
EGFR - inactivation (canonical)[Ground glass appearance]
DAB2(human)[Phospholipidosis - apotosis inhibitor]
Translocation of CAR from the cytosol to the nucleus is a subtype of nuclear transport: A process that of the directed movement of CAR from the cytoplasm to the nucleus.
Translocation of CAR from the cytosol to the nucleus
Translocation of CAR from the cytosol to the nucleus is a subtype of nuclear transport: A process that of the directed movement of CAR from the cytoplasm to the nucleus. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
Translocation of CAR from the cytosol to the nucleus [Ground glass appearance]
Hypofunction of gluconeogenesis is a subtype of hypofunction of biosynthesis: A process that performs a decreased or insufficient gluconeogenesis. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
hypofunction of gluconeogenesis [Ground glass appearance]
Hypofunction of gluconeogenesis is a subtype of hypofunction of biosynthesis: A process that performs a decreased or insufficient gluconeogenesis.
AMPK activation is a subtype of molecular activation: A process that changes the activity of the AMPK (AMP-activated protein kinase) to be higher. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
AMPK activation [Ground glass appearance]
AMPK dose not phosphorylate CAR directly but it does phosphorylate transcriptional coactivators such as p300, TORC2 (transducer of CREB), PGC1a.
Proteins which are inactvated by AMPK inculdes those that are involved in biosynthetic ATP-consuming reactions. AMPK inhibits a) glycogen synthesis via phosphorylation and inactivation of glycogen synthase, b) lipid synthesis by phosphorylation and inactivation of acetyl-CoA-carboxylase, whose product malonyl-CoA is an essential substrate for fatty acid synthesis, c) cholesterol synthesis by phosphorylation and inactivation HMG-CoA reductase, d)glucose synthesis via by phosphorylation and inactivation of TORC2, wich decreases expression of key gluconeogenetic enzymes such as PEPCK and glucose-6-phosphatase, and e) protein synthesis, and thus cell growth, by inhibiting the protein kinase mTOR. This adaptation is a rapid process.
MicroRNA-122 down-regulation is involved in phenobarbital-mediated activation of the constitutive androstane receptor.
AMPK has been long known to mediate phenobarbital-induced CAR activation. However, the result from the mechanistic study of the AMPK-dependent activation of CAR leave much to be desired. Phenobarbital seems to increase AMP/ATP ratio and ptomote liver kinase B1 (LKB1)-mediated AMPK activation.
phenobarbital - gluconeogenic inhibitor [Ground glass appearance]
FOXO1 (canonical)[Ground glass appearance]
Binding of activated CAR to FOXO1, a transcription factor that binds to IRS in the promoter region of glucogenetic genes such as PERCK1and G6pase, and supression of PERCK1 and G6Pase leading to decreased glucogenesis. Casarett and Doull's Toxicology 8th ed.
FOXO1 - inactive form (canonical)[Ground glass appearance]
Binding of activated CAR to FOXO1, a transcription factor that binds to IRS in the promoter region of glucogenetic gemes suc as PERCK1and G6pase, and supression of PERCK1 and G6Pase leading to decreased glucogenesis. Casarett and Doull's Toxicology 8th ed.
Any process that stops, prevents, or reduces the frequency, rate or extent of an ATP consuming process in the course of the ground glass degeneration via Constitutive Androstane Receptor (CAR). This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (sustained) .
negative regulation of ATP consuming via CAR activation (sustained) [Ground glass appearance]
Any process that stops, prevents, or reduces the frequency, rate or extent of gluconeogenesis. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
negative regulation of gluconeogenesis [Ground glass appearance]
Binding of activated CAR to FOXO1, a transcription factor that binds to IRS in the promoter region of glucogenetic genes such as PERCK1and G6pase, supresses PERCK1 and G6Pase leading to decreased glucogenesis. Casarett and Doull's Toxicology 8th ed.
GLUCOSE-6- phosphatase - gluconeogenic (canonical)[Ground glass appearance]
A role played by the entity involved in gluconeogenesis.
A role played by the entity which inhibits gluconeogenesis.
CAR -FOXO1 transcriptional repression factor (canonical)[Ground glass appearance]
AMPK - inhibitor (canonical)[Ground glass appearance]
Any process that stops, prevents, or reduces the frequency, rate or extent of gluconeogenesis in the course of ground grlass appearence. This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (sustained) .
negative regulation of gluconeogenesis (sustained) [Ground glass appearance]
Dab2(mouse)[Phospholipidosis - apotosis inhibitor]
A role played by the entity that activates AMPK activity.
FOXO1 inactivation is a subtype of inactivating: A process that changes the activity of the FOXO1 to be lower.
FOXO1 inactivation is a subtype of inactivating: A process that changes the activity of the FOXO1 to be lower. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
FOXO1 inactivation [Ground glass appearance]
Regulation of gluconeogenesis gene expression is a subtype of regulation of gene expression: A process that modulates the frequency, rate or extent of gluconeogenesis gene expression.
regulation of gluconeogenesis gene expression
Negative regulation of gluconeogenesis gene expression is a subtype of regulation of gluconeogenesis gene expression: A process that stops, prevents, or reduces the frequency, rate or extent of gluconeogenesis gene expression.
negative regulation of gluconeogenesis gene expression
Negative regulation of gluconeogenesis gene expression is a subtype of regulation of gluconeogenesis gene expression: A process that stops, prevents, or reduces the frequency, rate or extent of gluconeogenesis gene expression. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
negative regulation of gluconeogenesis gene expression [Ground glass appearance]
Negative regulation of G6Pase expression is a subtype of negative regulation of gene expression: A process that stops, prevents, or reduces the frequency, rate or extent of G6Pase expression.
negative regulation of G6Pase expression
Negative regulation of glucogenesis related gene expression is a subtype of negative regulation of gene expression: A process that stops, prevents, or reduces the frequency, rate or extent of glucogenesis related gene expression expression. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
negative regulation of glucogenesis related gene expression [Ground glass appearance]
Hypofunction of gluconeogenesis is a subtype of hypofunction of biosynthesis: A process that performs a decreased or insufficient gluconeogenesis. This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (sustained) .
hypofunction of gluconeogenesis (sustained) [Ground glass appearance]
Negative regulation of glucogenesis related gene expression is a subtype of negative regulation of gene expression: A process that stops, prevents, or reduces the frequency, rate or extent of glucogenesis related gene expression expression. This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (sustained) .
negative regulation of glucogenesis related gene expression (sustained) [Ground glass appearance]
FOXO1 inactivation is a subtype of inactivating: A process that changes the activity of the FOXO1 to be lower.This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (sustained) .
FOXO1 inactivation (sustained) [Ground glass appearance]
A role that represses the rate, timing and/or magnitude of transcription of FOXO1.
A role that activates, or increases the rate, timing and/or magnitude of transcription of gluconeogenic gene.
positive regulator of gluconeogenic gene transcription role
AMPK - activation state (canonical)[Ground glass appearance]
A role played by the entity which regulates carbohydrate metabolic process.
Increasing AMP/ATP ratio is a subtype of increasing ratio: A process that changes the ratio of AMP to ATP to be higher.
Increasing AMP/ATP ratio is a subtype of increasing ratio: A process that changes the ratio of AMP to ATP to be higher. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
increasing AMP/ATP ratio [Ground glass appearance]
Increasing AMP/ATP ratio is a subtype of increasing ratio: A process that changes the ratio of AMP to ATP to be higher. This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (sustained) .
increasing AMP/ATP ratio (sustained) [Ground glass appearance]
Any process that modulates the frequency, rate or extent of the chemical reactions resulting in the formation of precursor metabolites, substances from which energy is derived, and the processes involved in the liberation of energy from these substances regulated by phenobarbital. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
regulation of generation of precursor metabolites and energy by phenobarbital [Ground glass appearance]
Any process that stops, prevents, or reduces the frequency, rate or extent of an ATP consuming process in the course of the ground glass degeneration via Constitutive Androstane Receptor (CAR). This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
negative regulation of ATP consuming via CAR activation [Ground glass appearance]
Constitutive androstane receptor activation by phenobarbital_2 is a subtype of activating nuclear receptor: A process that changes the activity of the activating CAR ( constitutive androstane receptor) with a nuclear receptor role to be higher by phenobarbital. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
Phenobarbital indirectly activates CAR and CAR translocates from the cytoplasm to the nucleus.
constitutive androstane receptor activation by phenobarbital_2 [Ground glass appearance]
AMPK has been long known to mediate phenovarbital- induced CAR activation. However, it remains unclear how AMPK activation influences CAR nuclear translocation. AMPK dose not phosphorylate CAR directly but it does phosphorylate transcriptional coactivators such as p300, TORC2 (transducer of CREB), PGC1a. Casarett and Doull's 8th ed.
Any process that stops, prevents, or reduces the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of lipids. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
negative regulation of lipid biosynthetic process [Ground glass appearance]
AMPK - lipogenic inhibitor (canonical)[Ground glass appearance]
SREBP1 inactivation is a subtype of inactivating: A process that changes the activity of the SREBP1 to be lower. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
SREBP1 inactivation [Ground glass appearance]
CAR activation and iths associated activation of AMPK lead to the induction of Insig-1, together with Insig-2, plays a key role on the control of hepatic triglyceride and cholesterol synthesis. Induction of Insig1 results in repression of SREBP-1 which results in the down regulation of lipogenic enzymes and decrease hepatic triglyceride and cholesterol levels. Casarett and Doull's Toxicology 8th ed.
SREBP1 inactivation is a subtype of inactivating: A process that changes the activity of the SREBP1 to be lower.
Decreasing cholesterol is a subtype of decreasing lipid: A process that changes the amount of cholesterol to be lower. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
decreasing cholesterol [Ground glass appearance]
Decreasing hepatic triglyceride is a subtype of decreasing lipid: A process that changes the quantity of the hepatic triglyceride to be lower. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
decreasing hepatic triglyceride [Ground glass appearance]
Decreasing hepatic triglyceride is a subtype of decreasing lipid: A process that changes the quantity of the hepatic triglyceride in lysosomal membranes to be lower.
Decreasing cholesterol is a subtype of decreasing lipid: A process that changes the amount of cholesterol to be lower.
SREBP1 (canonical)[Ground glass appearance]
SREBP1 - inactive form (canonical)[Ground glass appearance]
A role played by the entity which positively regulates the formation of lipids.
A role played by the entity which positively regulates the formation of cholesterol.
cholesterol synthesis positive regulator role
Hyperfunction of mitochondrial fatty acid beta-oxidation is a subtype of hyperfunction of fatty acid beta-oxidation: A process that performs an excessive mitochondrial fatty acid beta-oxidation. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance.
hyperfunction of mitochondrial fatty acid beta-oxidation [Ground glass appearance]
CAR activators promote fatty-acid beta oxidation by repressing the expression of acetyl-coenzyme A (acetyl-CoA) carboxylase (both ACC1 and ACC2). Casarett and Doull's Toxicology 8th ed.
Acetyl-CoA carboxylase (ACC) is a complex multifunctional enzyme system. ACC is a biotin-containing enzyme which catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the rate-limiting step in fatty acid synthesis. There are two ACC forms, alpha and beta, encoded by two different genes. ACC-alpha is highly enriched in lipogenic tissues. The enzyme is under long term control at the transcriptional and translational levels and under short term regulation by the phosphorylation/dephosphorylation of targeted serine residues and by allosteric transformation by citrate or palmitoyl-CoA. Multiple alternatively spliced transcript variants divergent in the 5' sequence and encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
ACC1 (canonical)[Ground glass appearance]
ACC1 - inactive form (canonical)[Ground glass appearance]
A role played by the entity which positively regulates the formation of fatty acid.
fatty acid synthesis positive regulator role
ACC2 (canonical)[Ground glass appearance]
ACC2 - inactive form (canonical)[Ground glass appearance]
CAR - gluconeogenic inhibitor (canonical)[Ground glass appearance]
Negative regulation of ATP consuming is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of ATP consuming.
AMPK activation is a subtype of molecular activation: A process that changes the activity of the AMPK (AMP-activated protein kinase) to be higher. This process persists for a certain period or over a long period. This entity is a specific course-dependent process. This process can constitute the course of Ground glass appearance (sustained) .
AMPK activation (sustained) [Ground glass appearance]
The precise role of 5'AMP-activated kinase (AMPK) in cancer and its potential as a therapeutic target is controversial. Although it is well established that activation of this energy sensor inhibits the main anabolic processes that sustain cancer cell proliferation and growth, AMPK activation can confer on cancer cells the plasticity to survive under metabolic stress such as hypoxia and glucose deprivation, which are commonly observed in fast growing tumors.
ARK5 (canonical)[Ground glass appearance]
In the presence of wild-type LKB1, NUAK1 directly interacts with and phosphorylates p53 in vitro and in vivo. The phosphorylation of p53 induced by LKB1 required the kinase activity of NUAK1 and phosphorylation of NUAK1 at Thr211 by LKB1 was essential for its kinase activity, which leads to the conclusion that LKB1 activates NUAK1 and regulates phosphorylation of p53 through the NUAK1 kinase, at least partially. LKB1/NUAK1 activation leads to cell cycle arrest at the G(1)/S border by inducing expression of p21/WAF1. NUAK1 can regulate cell proliferation and exert tumor suppression through direct interaction with p53.
Sphingomyelin homeostasis imbalance is a subtype of lipid homeostasis imbalance: A process that becomes lacking a phospholipid homeostastasis balance. This process is dependent on the genetic and can constitute the course of Phospholipidosis (genetic).
sphingomyelin homeostasis imbalance [Phospholipidosis - genetic]
Phospholipid homeostasis imbalance is a subtype of lipid homeostasis imbalance: A process that becomes lacking a phospholipid homeostastasis balance. This process is dependent on the genetic and can constitute the course of Phospholipidosis (genetic).
phospholipid homeostasis imbalance [Phospholipidosis - genetic]
Sphingomyelin homeostasis imbalance is a subtype of lipid homeostasis imbalance: A process that becomes lacking a phospholipid homeostastasis balance. This entity is a specific course-dependent process. This process can constitute the course of Niemann Pick Disease Type A.
sphingomyelin homeostasis imbalance [Niemann Pick Disease Type A]
Sphingomyelin homeostasis imbalance is a subtype of lipid homeostasis imbalance: A process that becomes lacking a phospholipid homeostastasis balance. This entity is a specific course-dependent process. This process can constitute the course of Niemann Pick Disease Type B.
sphingomyelin homeostasis imbalance [Niemann Pick Disease Type B]
Sphingomyelin homeostasis imbalance is a subtype of lipid homeostasis imbalance: A process that becomes lacking a phospholipid homeostastasis balance. This entity is a specific course-dependent process. This process can constitute the course of Niemann Pick Disease Type A/ B.
sphingomyelin homeostasis imbalance [Niemann Pick Disease Type A/ B]
A role played by the entity that diminishes the rate of a chemical reaction competitively.
Leukocyte infiltration is a subtype of inflammatory cell inflow: A process that that moves the outside leukocyte cell to the inside.
Glutathione conjugation is a detoxication reaction. Four types of activation reaction have been recognized: direct-acting compounds, conjugates that are activated through cysteine conjugate beta-lyase, conjugates that are activated through redox cycling and lastly conjugates that release the original reactive parent compound. The glutathione S-transferases have three connections with the formation of biactivated conjugatesto make them more soluble for excretion.
Glutathione S-Transferases (GSTs; EC 2.5.1.18) are another major set of phase II conjugation enzymes. They can be found in the cytosol as well as being microsomal membrane-bound. Cytosolic GSTs are encoded by at least 5 gene families (alpha, mu, pi, theta and zeta GST) whereas membrane-bound enzymes are encoded by single genes. Soluble GSTs are homo- or hetero-dimeric enzymes (approximately 25KDa subunits) which can act on a wide range of endogenous and exogenous electrophiles. GSTs mediate conjugation using glutathione (GSH), a tripeptide synthesized from its precursor amino acids gamma-glutamate, cysteine and glycine. A generalized reaction isRX + GSH -> HX + GSRGlutathione conjugates are excreted in bile and converted to cysteine and mercapturic acid conjugates in the intestine and kidneys. GSH is the major, low molecular weight, non-protein thiol synthesized de novo in mammalian cells. As well as taking part in conjugation reactions, GSH also has antioxidant ability and can metabolize endogenous and exogenous compounds. The nucleophilic GSH attacks the electrophilic substrate forming a thioether bond between the cysteine residue of GSH and the electrophile. The result is generally a less reactive and more water-soluble conjugate that can be easily excreted. In some cases, GSTs can activate compounds to reactive species such as certain haloalkanes and haloalkenes. Substrates for GSTs include epoxides, alkenes and compounds with electrophilic carbon, sulfur or nitrogen centres. There are two types of conjugation reaction with glutathione: displacement reactions where glutathione displaces an electron-withdrawing group and addition reactions where glutathione is added to activated double bond structures or strained ring systems.
In the imbalance model, the basic units are as follows: 1) a functioning process (supply) for biological defense and maintaining homeostasis; 2) a functional demand process (demand) as toxic activity; 3) balance/imbalance between toxic activity and defense processes; and 4) outcome from organelles, cells, or tissues to the organ exhibiting toxicity manifestations. This entity is a compound state that inculdes step 1 to 4.
CTSB- apoptosis inhibitor (human)[Phospholipidosis - tumor metasitasis]
Phosphatidylinositol-4-Phosphate 3-Kinase Catalytic Subunit Type 2 Gamma [Hepatocarcinogenesis]
Phosphoinositide (PI) 3-kinases have been shown to have critical roles in signaling pathways that regulate proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking.
A novel class II phosphoinositide 3-kinase predominantly expressed in the liver and its enhanced expression during liver regeneration
A role played by the oncogene that is altered forms of normal cellular genes. Many proto-oncogenes are homologous to viral oncogenes and involved in the control of cell proliferation or differentiation. Mutations, amplifications or rearrangements of proto-oncogenes lead to upregulated or deregulated cell growth and allow them to function as oncogenes.
Normal cellular genes at a stage prior to carcinogenesis. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Proto-oncogenes have names of the form c-onc.
A role of the cytoplasmic proteins that bind to nascent or unfolded polypeptides and ensure correct folding or transport. Chaperone proteins do not covalently bind to their targets and do not form part of the finished product. Heat-shock proteins are an important sub set of chaperones. Three major families are recognised, the chaperonins (groEL and hsp60), the hsp70 family and the hsp90 family. Outside these major families are other proteins with similar functions including nucleoplasmin, secB and T-cell receptor associated protein.
Ctsb- apoptosis inhibitor (mouse)[Phospholipidosis - apoptosis inhibitor]
Ctsb- apoptosis inhibitor (mouse)[Phospholipidosis - tumor metasitasis]
Recycling endosome dysfunction is a subtype of dysfunctioning: A process that performs an abnormal and incomplete recycling endosomal function. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (severe).
recycling endososomal dysfunction [Phospholipidosis (severe) ]
Recycling endosome dysfunction is a subtype of dysfunctioning: A process that performs an abnormal and incomplete recycling endosomal function. And the degree is severe.
It has been shown that insulin blunts hepatocyte ALAS1 induction, by disrupting the interaction of FOXO1 (forkhead box O1) and PGC-1α (peroxisome-proliferator-activated receptor γ co-activator 1α).
Hyperfunction of phospholipid biosynthesis is a subtype of hyperfunction of biosynthesis: A process that performs an excessive heme biosynthesis.
Propionyl-CoA Carboxylase Alpha Subunit [Hepatocarcinogenesis]
Fatal propionic acidemia in mice lacking propionyl-CoA carboxylase and its rescue by postnatal, liver-specific supplementation via a transgene.
Propionic acidemia: mutation update and functional and structural effects of the variant alleles. Mutations in the PCCA or PCCB genes, encoding both subunits of propionyl-CoA carboxylase, result in propionic acidemia, a life-threatening inborn error of metabolism with autosomal recessive inheritance. For the PCCA gene, the main molecular effect of the expressed mutations is related to protein instability, except two mutations in the active site predictably affecting ATP binding.
Identification of early proteomic markers for hepatic steatosis.
PPARA lipid metabolism regulator (canonical)[Eosinophilic granular degeneration]
Tumor tissue is a subtype of abnormal cellular tissue that consists of tumor cells .
Hypofunction of eidocytic recycling from ER to mitochondrial membrane is a subtype of hypofunction of transport: A process that performs a decreased or insufficient endocytic recycling.
Hypofunction of eidocytic recycling from ER to mitochondrial membrane is a subtype of hypofunction of transport: A process that performs a decreased or insufficient endocytic recycling. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
hypofunction of endocytic recycling [Phospholipidosis (severe) ]
Involvement of the p38 mitogen-activated protein kinase cascade in hepatocellular carcinoma.
Mechanism of action of sulforaphane: inhibition of p38 mitogen-activated protein kinase isoforms contributing to the induction of antioxidant response element-mediated heme oxygenase-1 in human hepatoma HepG2 cells.
The mitogen-activated protein (MAP) kinases p38 and extracellular signal-regulated kinase (ERK) are involved in hepatocyte-mediated phenotypic switching in prostate cancer cells.
Negative regulation of release of arachidonic acid from cell membrane is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of the release of arachidonic acid from cell membrane.
negative regulation of release of arachidonic acid from cell membrane
Dissociation of FLCN:FNIP complex is a subtype of detaching: A process that disaggregates the FLCN:FNIP complex. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
Dissociation of FLCN:FNIP complex [Phospholipidosis (severe)]
Dissociation of FLCN:FNIP complex is a subtype of detaching: A process that disaggregates the FLCN:FNIP complex.
Fas cell surface death receptor [Hepatocarcinogenesis]
CD95/Fas promotes tumour growth: Loss of CD95 in mouse models of ovarian cancer and liver cancer reduces cancer incidence as well as the size of the tumours. The tumorigenic activity of CD95 is mediated by a pathway involving JNK and c-Jun.
Moreover, mitochondrial-free cholesterol sensitizes liver cells to TNFα- and Fas-mediated steatohepatitis and causes mitochondrial-reduced glutathione (mGSH) depletion, which is also reported in animal models and patients with NASH.
This gene is located within the Smith-Magenis syndrome region on chromosome 17. Mutations in this gene are associated with Birt-Hogg-Dube syndrome, which is characterized by fibrofolliculomas, renal tumors, lung cysts, and pneumothorax. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling.
Molecular Genetics and Clinical Features of Birt-Hogg-Dubé-Syndrome
Complex formation by the human Rad51B and Rad51C DNA repair proteins and their activities in vitro.
RAD51 localization and activation following DNA damage.
A role played by the entity which regulates the metabolism.
TOR signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the TOR (Target of rapamycin) .
ZNF385B is characteristically expressed in germinal center B cells and involved in B-cell apoptosis. Ectopic expression of the longest transcript variant of ZNF385B, possessing four ZF domains, induced upregulation of PERP and FAS/CD95, a downstream target of p53, and activation of caspase, resulting in apoptosis induction. \ However, a ZNF385B deletion mutant with three ZF domains corresponding to shorter isoforms, did not induce upregulation; rather it inhibited apoptosis induced by CD20 cross-linking and BCR stimulation. The direct binding of ZNF385B with p53 has suggested the involvement of ZNF385B in B-cell apoptosis via modulation of p53 transactivation; our data indicate that ZNF385B characteristically expressed in GC B cells has both proapoptotic and antiapoptotic activities depending on the type of isoform and should be a novel player in GC B-cell selection.
ZNF385B and VEGFA are strongly differentially expressed in serous ovarian carcinomas and correlate with survival.
Negative regulation of release of arachidonic acid from cell membrane is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of the release of arachidonic acid from cell membrane. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
negative regulation of release of arachidonic acid from cell membrane [Phospholipidosis]
hepatoma-derived growth factor, related protein 3 [Hepatocarcinogenesis]
Enhances DNA synthesis and may play a role in cell proliferation.
A new member of a hepatoma-derived growth factor gene family can translocate to the nucleus.
Depletion of hepatoma-derived growth factor-related protein-3 induces apoptotic sensitization of radioresistant A549 cells via reactive oxygen species-dependent p53 activation.
HRP-3 protects the hepatoma cells from glucose deprivation-induced apoptosis: Silence of HRP-3 prevented the de-phosphorylation of S6K1 induced by glucose deprivation, which was an essential molecular event for HCC cell survival in energy pressure. Glucose deprivation-induced HRP-3 up-regulation potentially plays a major role in protecting HCC cells against apoptosis caused by energy pressure.
TOR signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the TOR (Target of rapamycin) . This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis .
TOR signaling (primitive) [Phospholipidosis]
The directed movement of tumor inhibitor from the lysosome.
release of tumor inhibitor from lysosome
Protein Inhibitor Of Activated STAT 3 [Hepatocarcinogenesis]
Isolation and chromosomal assignment of a human gene encoding protein inhibitor of activated STAT3 (PIAS3).
STAT3 activation in monocytes accelerates liver cancer progression.
PIAS3 activates the intrinsic apoptotic pathway in non-small cell lung cancer cells independent of p53 status.
Induction of human UGT2B7 gene expression by cytotoxic anticancer drugs in liver cancer HepG2 cells. UGT2B7 as a p53 target gene. The cytotoxic drug induced UGT2B7 activity in target liver cancer cells or possibly in normal liver cells may affect the therapeutic efficacy of coadministered cytotoxic drugs (e.g., epirubicin) and noncytotoxic drugs (e.g., morphine), which are UGT2B7 substrates.
A large number of case-control studies have investigated this hypothesis and these studies identified numerous UGT polymorphisms in UGT1A and UGT2B genes as genetic risk factors for a wide variety of cancers, including bladder, breast, colorectal, endometrial, esophageal, head and neck, liver, lung, prostate, and thyroid.
The directed movement of tumor inhibitor from the lysosome. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
release of tumor inhibitor from lysosome [Phospholipidosis]
Mutual inhibition between YAP and SRSF1 maintains long non-coding RNA, Malat1-induced tumourigenesis in liver cancer.
Splicing factor 2/alternative splicing factor contributes to extracellular signala89regulated kinase activation in hepatocellular carcinoma cells.
Notch3 overexpression promotes anoikis resistance in epithelial ovarian cancer via upregulation of COL4A2. (
A role played by the entity which negatively regulates the process of tumor cell proliferation.
negative regulator of tumor cell proliferation
Identification of a novel ionizing radiation-induced nuclease, AEN, and its functional characterization in apoptosis.
ISG20L1 is a p53 family target gene that modulates genotoxic stress-induced autophagy.
A role played by the entity which negatively regulates the process of cell proliferation.
negative regulator of cell proliferation
Forming adduct is a subtype of having extra parts: A process that changes to have connection or association with another entity.
Abnormal cell tissue is a subtype of cellular tissue that consists of abnormal cells and tissues.
The chemical reaction resulting in the breakdown of FNIP2, which is mediated by the proteasome.
proteasome-mediated ubiquitin-dependent FNIP2 catabolic process
The chemical reaction resulting in the breakdown of FNIP2, which is mediated by the proteasome. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis
proteasome-mediated FNIP2 degradation [Phospholipidosis]
HMGCS2 transcription is heavily regulated by FOXA2, mTOR, PPARα, and FGF21.
Human HMGCS2 regulates mitochondrial fatty acid oxidation and FGF21 expression in HepG2 cell line. HMGCS2 expression is both sufficient and necessary to the control of fatty acid oxidation in these cells. Next, we examined the expression pattern of several PPARα target genes in this now "ketogenic" HepG2 cell line. FGF21 (fibroblast growth factor 21) expression was specifically induced by HMGCS2 activity or by the inclusion of the oxidized form of ketone bodies (acetoacetate) in the culture medium
HMGCS2 enhances invasion and metastasis via direct interaction with PPARα to activate Src signaling in colorectal cancer and oral cancer.
Docosahexaenoic acid (DHA, C22:6, n-3), eicosapentaenoic acid (EPA, C20:5, n-3), arachidonic acid (AA, C20:4, n-6), and glucose increased HMGCS2 mRNA and protein levels in HepG2 hepatoma cells. The effect of n-6 AA resulted significantly higher than that of n-3 PUFA, but when combined all these molecules were far less efficient. Insulin reduced HMGCS2 mRNA and protein levels in HepG2 cells, even when treated with PUFA and monosaccharides. While peroxysome proliferator activated receptor α (PPAR-α) agonist WY14643 increased HMGCS2 expression, this treatment was unable to affect PUFA-mediated regulation of HMGCS2 expression. Forkhead box O1 (FoxO1) inhibitor AS1842856 reduced HMGCS2 expression and suppressed induction promoted by fatty acids. Cells treatment with liver X receptor alpha (LXRα) agonist T0901317 reduced HMGCS2 mRNA, indicating a role for this transcription factor as suppressor of HMGCS2 gene.
PPARalpha activation is a subtype of activating nuclear receptor: A process that changes the activity of the activating PPAR alpha ( (Peroxisome Proliferator Activated Receptor Alpha)) with a nuclear receptor role to be higher. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
capping protein regulator and myosin 1 linker 3
dentifying LRRC16B as an oncofetal gene with transforming enhancing capability using a combined bioinformatics and experimental approach.
Distinct roles for CARMIL isoforms in cell migration. Cell Migration and Invadopodia Formation Require a Membrane-binding Domain of CARMIL2.
Cyclin B2 and p53 control proper timing of centrosome separation. PMID:9539739 A centrosomal route for cancer genome instability. Cyclin B2 is now shown to control a pathway - involving the centrosomal kinases aurora A and Plk1 and the tumour suppressor p53 - the alteration of which causes defective centrosome separation, aneuploidy and tumour development. PMID:24875738
Cyclin B2 suppresses mitotic failure and DNA re-replication in human somatic cells knocked down for both cyclins B1 and B2.
The roles of cyclin A2, B1, and B2 in early and late mitotic events.
We found that cyclin G1 levels were increased in normal tissue compared with HCC tissue and vary over the course of the cell cycle, with equal distribution between the nucleus and cytoplasm observed during normal serum support and accelerated release from the nucleus into the cytoplasm observed during serum starvation.
The CENPE gene encodes a large kinetochore-associated kinesin-like motor protein required for spindle microtubule capture and attachment at the kinetochore during cell division
Reduced expression of cenp-e in human hepatocellular carcinoma.
p21waf1/Cip1 partially mediates apoptosis in hepatocellular carcinoma cells.
p21 promotes sustained liver regeneration and hepatocarcinogenesis in chronic cholestatic liver injury.
Gene polymorphisms of cellular senescence marker p21 and disease progression in non-alcohol-related fatty liver disease.
Molecular cloning and functional analysis of a novel oncogene, cancer-upregulated gene 2 (CUG2). CUG2 is a novel tumor-associated gene that is commonly activated in various human cancers and exhibits high transforming activities; it possibly belongs to a transcription regulator family that is involved in tumor biogenesis.
Premitotic assembly of human CENPs -T and -W switches centromeric chromatin to a mitotic state. The CENP-T/W complex assembles through a dynamic exchange mechanism in late S-phase and G2, is required for mitosis in each cell cycle and does not persist across cell generations, properties reciprocal to those measured for CENP-A. We propose that the CENP-A and H3-CENP-T/W nucleosome components of the centromere are specialized for centromeric and kinetochore activities, respectively.
carboxypeptidase Q [Hepatocarcinogenesis]
cytochrome P450, family 3, subfamily A, polypeptide 5 [Hepatocarcinogenesis]
Broad but distinct role of pregnane x receptor on the expression of individual cytochrome p450s in human hepatocytes. Introduction of the hPXR-siRNA adenoviral vector reduced the level of PXR mRNA. After infection with Ad hPXR-siRNA, the basal and ligand-activated CYP2A6, CYP2C8, CYP3A4 and CYP3A5 mRNA levels were decreased significantly in dose-dependent manners, whereas CYP2B6, CYP2C9 and CYP2C19 mRNA levels were moderately influenced after infection with Ad hPXR-siRNA. These data suggest the distinct PXR influences on the regulation of these genes.
CYP3A5 Functions as a Tumor Suppressor in Hepatocellular Carcinoma by Regulating mTORC2/Akt Signaling.
EIF1 (Eukaryotic Translation Initiation Factor 1) is a Protein Coding gene. Among its related pathways are Translation Factors and RNA transport. GO annotations related to this gene include poly(A) RNA binding and translation factor activity, RNA binding. An important paralog of this gene is EIF1B.
eukaryotic translation initiation factor 1 [Hepatocarcinogenesis]
The chemical reactions and pathways resulting in the formation of ketones, a class of organic compounds that contain the carbonyl group, CO, and in which the carbonyl group is bonded only to carbon atoms. The general formula for a ketone is RCOR, where R and R are alkyl or aryl groups. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
ketone biosynthetic process[Phospholipidosis]
The key irreversible step in ketogenesis is synthesis of 3-hydroxy-3-methylglutaryl-CoA by HMGCS2. Conversely, the rate limiting step in ketolysis is conversion of acetoacetate to acetoacetyl-CoA by OXCT1. HMGCS2 transcription is heavily regulated by FOXA2, mTOR, PPARα, and FGF21. ketogenic diets suppress fatty acid synthesis enzymes including SCD1. Instead, PPARα, a regulator of ketogenic genes, is strongly induced, as is one of its crucial downstream targets, FGF21, resulting in increased transcription of ketogenic enzymes, such as HMGCS2.
Hypofunction of anti-oxidative stress is a subtype of hypofunctioning: A process that performs a decreased or insufficient anti-oxidative stress function.
Glypican-3-mediated oncogenesis involves the Insulin-like growth factor-signaling pathway.
Dysplastic nodules with glypican-3 positive immunostaining: a risk for early hepatocellular carcinoma. GPC3-positive DN, especially GPC3-positive HGDN, was really a late premalignant lesion of HCC.
Mutations in GPC3, a glypican genecause the Simpson-Golabi-Behmel overgrowth syndrome.
Hypofunction of anti-oxidative stress is a subtype of hypofunctioning: A process that performs a decreased or insufficient anti-oxidative stress function. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis
hypofunction of anti-oxidative stress[Phospholipidosis]
Regulation of cell cycle progression and gene expression by H2A deubiquitination.
RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins.
RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly.
RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins. We show that RNF168 interacts with ubiquitylated H2A, assembles at DSBs in an RNF8-dependent manner, and, by targeting H2A and H2AX, amplifies local concentration of lysine 63-linked ubiquitin conjugates to the threshold required for retention of 53BP1 and BRCA1.
PLA2G15 is to date the first and only identified lysosomal phospholipase A.
PLA2G15 (canonical) positively regulator of immune response[Phospholipidosis]
An active focus of work on the role of PLA2G15 in disease has been in the areas of inflammation and host defense. Phospholipase A2s in general play multiple roles in host response to pulmonary infection and inflammation. They have been implicated in the production of eicosanoids, cytokines, and in direct bacteriocidal activities.
Inhibin beta E is upregulated by drug-induced endoplasmic reticulum stress as a transcriptional target gene of ATF4.
Tetracyclines cause cell stress-dependent ATF4 activation and mTOR inhibition.
A subgroup of Hepatocellular adenomas (HCA) characterized by fusion of the INHBE and GLI1 genes and activation of sonic hedgehog pathway.
integrin, beta 1 (fibronectin receptor, beta polypeptide, antigen CD29 includes MDF2, MSK12) [Hepatocarcinogenesis]
Beta-1 integrins regulate chondrocyte rotation, G1 progression, and cytokinesis.
LPS-induced TLR4 signaling in human colorectal cancer cells increases beta1 integrin-mediated cell adhesion and liver metastasis: The results indicate that stimulation of the TLR4/MD2 complex by LPS activates PI3K/AKT signaling and promotes downstream beta1 integrin function, thereby increasing the adhesiveness and metastatic capacity of CRC cells.
This gene encodes a nuclear protein with a JmjC domain. JmjC domain-containing proteins are predicted to function as protein hydroxylases or histone demethylases. This protein was first identified as a putative phosphatidylserine receptor involved in phagocytosis of apoptotic cells; however, subsequent studies have indicated that it does not directly function in the clearance of apoptotic cells, and questioned whether it is a true phosphatidylserine receptor. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008
jumonji domain containing 6 [Hepatocarcinogenesis]
A receptor for phosphatidylserine-specific clearance of apoptotic cells.
Jmjd6 catalyses lysyl-hydroxylation of U2AF65, a protein associated with RNA splicing.
Energy supply is a subtype of providing process to perform a meta-function “to provide energy.
Any process that increases the rate or frequency of cell death. Cell death is the specific activation or halting of processes within a cell so that its vital functions markedly cease, rather than simply deteriorating gradually over time, which culminates in cell death.
Any process that stops, prevents or reduces the frequency, rate or extent of tmitochondrial electron transport, ubiquinol to cytochrome c
negative regulation of mitochondrial electron transport, ubiquinol to cytochrome c
Any process that decreases the rate or frequency of cell death. Cell death is the specific activation or halting of processes within a cell so that its vital functions markedly cease, rather than simply deteriorating gradually over time, which culminates in cell death.
Pro-protein convertase gene expression in human breast cancer. 9185698
The secretory proprotein convertases furin, PC5, and PC7 activate VEGF-C to induce tumorigenesis.
Evaluation of genome-wide loci of iron metabolism in hereditary hemochromatosis identifies PCSK7 as a host risk factor of liver cirrhosis.
negative regulation of potassium ion transport [Phospholipidosis]
Any process that increases the rate, frequency or extent of macrophage derived foam cell differentiation. Macrophage derived foam cell differentiation is the process in which a macrophage acquires the specialized features of a foam cell. A foam cell is a type of cell containing lipids in small vacuoles and typically seen in atherosclerotic lesions, as well as other conditions. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
positive regulation of macrophage derived foam cell differentiation [Phospholipidosis]
Malfunctioning of insulin signaling is a subtype of malfunctioning process: A process that cannot perform insulin signaling [biological] appropriately or cannot realize it at all. This entity is a specific course-dependent process. This process can constitute the course of Phosphoipidosis.
malfunctioning of insulin signaling [Phospholipidosis]
kcnma1 expression is downregulated in white adipose tissue of mice fed a high-fat diet and in hypertrophied adipocytes. Furthermore, inhibition of kcnma1 expression or treatment with a BK channel blocker attenuated insulin-induced Akt phosphorylation in mature adipocytes. These results strongly indicate that KCNMA1 contributes to the regulation of insulin signalling in mature adipocytes.
ribonuclease, RNase A family, 1-like 2 (pancreatic)
PC4 promotes genome stability and DNA repair through binding of ssDNA at DNA damage sites.
Purification, cloning, and characterization of a human coactivator, PC4, that mediates transcriptional activation of class II genes.
KCNMA1, a pore-forming α-subunit of BK channels, regulates insulin signalling in mature adipocytes.
twist family bHLH transcription factor 1 [Hepatocarcinogenesis]
Twist-1 is a PPAR-delta-inducible, negative-feedback regulator of PGC-1-alpha in brown fat metabolism.
STAT3 cooperates with Twist to mediate epithelial-mesenchymal transition in human hepatocellular carcinoma cells.
Thymidylate synthase catalyzes the methylation of deoxyuridylate to deoxythymidylate using 5,10-methylenetetrahydrofolate (methylene-THF) as a cofactor. This function maintains the dTMP (thymidine-5-prime monophosphate) pool critical for DNA replication and repair. The enzyme has been of interest as a target for cancer chemotherapeutic agents. It is considered to be the primary site of action for 5-fluorouracil, 5-fluoro-2-prime-deoxyuridine, and some folate analogs. Expression of this gene and that of a naturally occuring antisense transcript rTSalpha (GeneID:55556) vary inversely when cell-growth progresses from late-log to plateau phase. [provided by RefSeq, Jul 2008] https://www.ncbi.nlm.nih.gov/gene/7298
thymidylate synthetase [Hepatocarcinogenesis]
The process in which one or more ubiquitin groups are added to a protein.
genetic information carrier role is a subtype of role dependent on transmitting genetic information process
Any process that activates or increases the frequency, rate or extent of glutathione biosynthetic process. This entity is a specific course-dependent process. This process can constitute the course of Glutathione depletion.
positive regulation of glutathione biosynthetic process [Glutathione depletion]
Any process that stops, prevents or reduces the frequency, rate or extent of the transfer of electrons from succinate to ubiquinone.
negative regulation of mitochondrial electron transport, succinate to ubiquinone
Malfunctioning of cobalamin biosynthetic process is a subtype of malfunctioning process: A process that cannot perform cobalamin biosynthetic process appropriately or cannot realize it at all.
malfunctioning of cobalamin biosynthetic process
Malfunctioning of cobalamin biosynthetic process is a subtype of malfunctioning process: A process that cannot perform cobalamin biosynthetic process appropriately or cannot realize it at all. This entity is a specific course-dependent process. This process can constitute the course of Phosphoipidosis.
malfunctioning of cobalamin biosynthetic process[Phospholipidosis]
CAR - apotosis inhibitor (canonical)[Ground glass appearance]
NCR3LG1 (predicted)(human)[Phospholipidosis]
A protein modification process in which one or more groups of a small protein, such as ubiquitin or a ubiquitin-like protein, are covalently attached to a target protein.
protein modification by small protein conjugation
Any process that stops, prevents or reduces the frequency, rate or extent of mitochondrial electron transport, NADH to ubiquinone. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
negative regulation of mitochondrial electron transport, NADH to ubiquinone [Mitochondrial disorder]
A process that results in the assembly, arrangement of constituent parts of a lipid droplet.
A process that results in the assembly, arrangement of constituent parts of a lipid droplet. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
lipid droplet formation [Phospholipidosis]
The orderly movement of a macrophage from one site to another. This entity is a specific course-dependent process. This process can constitute the course of phospholipidosis.
SPON2(human) - tumor metastasis inhibitor[Phospholipidosis]
A role played by the entity which negatively regulates the tumor metastasis.
SPON2(human) - immune responsor[Phospholipidosis]
Hyperfunction of drug metabolism phase II is a subtype of hyperfunction of drug metabolism: A process that performs an excessive drug metabolism phase II. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
hyperfunction of drug metabolism phase II [Phospholipidosis]
Any process that stops, prevents or reduces the frequency, rate or extent of the transfer of electrons from succinate to ubiquinone. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
negative regulation of mitochondrial electron transport, succinate to ubiquinone [Mitochondrial disorder]
Any process that stops, prevents or reduces the frequency, rate or extent of tmitochondrial electron transport, ubiquinol to cytochrome c. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
negative regulation of mitochondrial electron transport, ubiquinol to cytochrome c [Mitochondrial disorder]
Drug-, radiation-induced, or spontaneous injuries to DNA that introduce deviations from its normal double-helical conformation. These changes include structural distortions that interfere with replication and transcription, as well as point mutations that disrupt base pairs and exert damaging effects on future generations through changes in DNA sequence. If the damage is minor, it can often be repaired (DNA repair); extensive damage can induce apoptosis. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
For instance APAP and troglitazone can induce mtDNA strand breaks which eventually lead to a reduction of mtDNA levels. Indeed, damaged mtDNA molecules harboring numerous strand breaks can be rapidly degraded by mitochondrial endonucleases.
NAFLD has been associated with higher hepatic expression of the inducible nitric oxide (NO) synthase (iNOS), mainly as a consequence of tumor necrosis factor‐α (TNF‐α) overproduction by the Kupffer cells. NO can readily react with the superoxide anion, thus generating the RNS peroxynitrite, which has deleterious effects on mitochondrial function and genome. It is likely that this event triggers a vicious cycle since mitochondrial ROS are able to oxidatively damage nearby MRC enzymes and mtDNA TNF‐α is able to impair MRC activity, possibly by inducing hypoxia inducible factor‐1α (HIF‐1α) and mtDNA damage. In addition to ROS, reactive nitrogen species (RNS) and lipid peroxidation products are able to damage mtDNA.
Alcohol-mediated damage of mitochondrial DNA (mtDNA) also impairs cellular energy metabolism via enhanced formation of reactive oxygen species (ROS).
Just like in NASH, oxidative stress, mitochondrial dysfunction, and oxidized mtDNA also contribute to the progression of HCC through influences on inflammation, cell death, and ER stress. Moreover, a diet rich in fructose is associated with increased oxidative mtDNA lesions in rat liver coupled with reduced mitochondrial repair capacity and rats consuming a diet high in fat and rich in fructose have increased hepatocyte damage, inflammation, and lipid peroxidation coupled with impaired mitochondrial respiration and activity.
Any process that increases the rate or frequency of tumor cell death.
Any process that increases the rate or frequency of tumor cell death. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
positive regulation of tumor cell death [Phospholipidosis]
Negative regulation of heat generation is a subtype of negative regulation process: Any process that stops, prevents, or reduces the rate or extent of heat generation. This process can constitute the course of Mitochondrial disorder.
down regulation of heat generation [Mitochondrial disorder]
down-regulation of heat generation [Mitochondrial disorder]
downregulation of heat generation [Mitochondrial disorder]
inhibition of heat generation [Mitochondrial disorder]
negative regulation of heat generation [Mitochondrial disorder]
Negative regulation of oxidative phosphorylation is a subtype of negative regulation process: Any process that stops, prevents or reduces the frequency, rate or extent of the oxidative phosphorylation. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
negative regulation of oxidative phosphorylation [Mitochondrial disorder]
Some lipid derivatives such as FAs can directly inhibit several enzymes involved in MRC and OXPHOS.
Chronic alcohol consumption alters mitochondrial oxidative phosphorylation in the liver by suppressing the synthesis of respiratory complex proteins.
In general, damaged mitochondria accumulation can cause excessive ROS production, which will destroy mitochondrial oxidative phosphorylation and substrate oxidation, thereby inhibiting fatty acid oxidative degradation and accelerating fatty acid accumulation.
Malfunctioning of TCA cycle is a subtype of malfunctioning of metabolism: A process that cannot perform a tricarboxylic acid cycle appropriately or cannot realize it at all. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
malfunctioning of TCA cycle [Mitochondrial disorder]
Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver. Here, we provide several lines of evidence indicating that induction of biosynthesis through hepatic anaplerotic/cataplerotic pathways is energetically backed by elevated oxidative metabolism and hence contributes to oxidative stress and inflammation during NAFLD. First, in murine livers, elevation of fatty acid delivery not only induced oxidative metabolism, but also amplified anaplerosis/cataplerosis and caused a proportional rise in oxidative stress and inflammation. Second, loss of anaplerosis/cataplerosis via genetic knockdown of phosphoenolpyruvate carboxykinase 1 (Pck1) prevented fatty acid-induced rise in oxidative flux, oxidative stress, and inflammation. Though all tissues support minor activities of anaplerosis and cataplerosis, these pathways are a major function of liver TCA cycle, where anaplerosis and cataplerosis are required for shuttling reducing equivalents (RE) and biosynthetic substrates related to ureagenesis, amino acid synthesis, lipogenesis, and most prominently, gluconeogenesis (GNG) (1) On the whole, the data indicate that increased flux through anaplerotic/cataplerotic pathways not only contributes to dysregulation of downstream nutrients (e.g., glycemia and lipidemia), but also triggers oxidative metabolism and altered antioxidant capacity that contribute to the development of oxidative stress, inflammation, and insulin resistance (Figure 8B and Supplemental Table 2).
Metabolic reprogramming by PCK1 promotes TCA cataplerosis, oxidative stress and apoptosis in liver cancer cells and suppresses hepatocellular carcinoma. Supporting this notion, PCK1 expression in SK-Hep-1 dramatically reduced cellular ATP level by 4 folds in cells cultured in low glucose medium, but not in normal medium (Fig. 4c). In addition, supplement of dimethyl-α-KG may also increase cellular ATP level and alleviate energy stress, as indicated by the decreased phosphorylation of AMPKα1 and ACC (Fig. 5f).
Increasing acetyl CoA is a subtype of increasing quantity: A process that changes the amount of acetyl CoA to be larger. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder].
increasing acetyl CoA [Mitochondrial disorder]
Hepatic ketogenesis was also augmented in mice fed a high‐fat diet (HFD), thus suggesting that higher acetyl‐CoA generation by way of mtFAO is followed by efficient KB production.
Increasing volume of mitochondria is a changing process to change the volume of the mitochondria to increase. This entity is a specific course-dependent process. This process can constitute the course of Lipidosis.
increasing volume of mitochondria [lipidosis]
Any biological process that results in permanent cessation of tumor cells.
Increasing uptake amount of mitochondrial proton is a subtype of increasing quantity: A process that changes the uptake amount of mitochondrial proton to be higher.
increasing uptake amount of mitochondrial proton ion
Increasing uptake amount of mitochondrial proton is a subtype of increasing quantity: A process that changes the uptake amount of mitochondrial proton to be higher. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
increasing uptake amount of mitochondrial proton ion [Mitochondrial disorder]
Negative regulation of tumor cell proliferation is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of tumor cell proliferation. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
negative regulation of tumor cell proliferation [Phospholipidosis]
Any process that enables the transfer of protons from mitochondrial intermembrane space into mitochondrial matrix, dissipating the proton gradient across the mitochondrial inner membrane established by the electron transport chain during the oxidative phosphorylation (proton leak). Proton leak uncouples the processes of electron transport/proton generation and ATP synthesis.
Any process that activates or increases the frequency, rate or extent of oxidative phosphorylation uncoupling. Oxidative phosphorylation uncoupling is a process that enables the transfer of protons from mitochondrial intermembrane space into mitochondrial matrix, dissipating the proton gradient across the mitochondrial inner membrane established by the electron transport chain during the oxidative phosphorylation (proton leak). Proton leak uncouples the processes of electron transport/proton generation and ATP synthesis.
positive regulation of oxidative phosphorylation uncoupling
Any process that activates or increases the frequency, rate or extent of oxidative phosphorylation uncoupling. Oxidative phosphorylation uncoupling is a process that enables the transfer of protons from mitochondrial intermembrane space into mitochondrial matrix, dissipating the proton gradient across the mitochondrial inner membrane established by the electron transport chain during the oxidative phosphorylation (proton leak). Proton leak uncouples the processes of electron transport/proton generation and ATP synthesis. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
positive regulation of oxidative phosphorylation uncoupling [Mitochondrial disorder]
Energy supply is a subtype of providing process to perform a meta-function “to provide energy. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (normal condition).
energy supply [Phospholipidosis(normal)]
Increasing energy is a subtype of increasing quantity: A process that changes the amount of energy to be larger. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (normal condition).
increasing energy [Phospholipidosis (normal)]
Decreasing energy is a subtype of decreasing quantity: A process that changes the amount of energy to be smaller.
Decreasing energy is a subtype of decreasing quantity: A process that changes the amount of energy to be smaller. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
Ctsb (mouse)[Niemann-Pick disease - fibrosis]
Cathepsin B Overexpression Due to Acid Sphingomyelinase Ablation Promotes Liver Fibrosis in Niemann-Pick Disease
Hepatic fibrosis is a subtype of fibrosis: A process that replaces liver tissues to fibrous connective tissues, usually as a consequence of inflammation or other injury. This entity is a specific course-dependent process. This process can constitute the course of Niemanne-Pick disease.
CTSB (human)Niemann-Pick disease - fibrosis]
ceramide accumulation is a subtype of accumulation of substances in a biological object: A process that keeps ceramide in an organism, tissue, organelle, or cell.
A process that results in the breakdown of the extracellular matrix. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (excessive defense).
extracellular matrix disassembly [Phospholipidosis]
Cathepsin B: association with plasma membrane in metastatic tumors. Localization of hydrolytic enzymes in the plasma membrane of metastatic tumor cells could result in focal dissolution of the extracellular matrix and thereby invasion and metastasis.
A process that performs a decreased or insufficient cholesterol efflux
hypofunction of cholesterol efflux from hepatoyte
A process that performs a decreased or insufficient cholesterol export. This entity is a specific course-dependent process. This process can constitute the course of Niemann-Pick disease.
hypofunction of cholesterol efflux [Niemann-pick disease]
Although tissues from mice or patients with NPA and NPB disease accumulate SM primarily in endolysosomes, cholesterol also increases as a secondary consequence (Huang and Feigenson, 1999; Radhakrishnan et al., 2000; Ridgway, 2000). While the underlying mechanism of cholesterol loading is not well understood, it is known that SM and cholesterol exhibit a high affinity for each other. Indeed, SM binds cholesterol with high affinity (Slotte, 1999; Ridgway, 2000), resulting in the sequestration and subsequent decrease in the efflux of cholesterol out of lysosomes, impairing the esterification of cholesterol by acyl-CoA:cholesterol acyl transferase in the ER. These events are in line with findings in macrophages from ASMase−/− mice or in macrophages from wild type mice enriched with exogenous SM, which results in increased lysosomal cholesterol content because of decreased cholesterol efflux (Leventhal et al., 2001). Interestingly, it has been described that ASMase is not only active in lysosomes, but it exhibits a secretory form that acts on the plasma membrane to generate ceramide from SM hydrolysis in response to stress (Falcone et al., 2004; Charruyer et al., 2005). This event, in turn, reorganizes membrane lipid domains, called “rafts,” which trigger downstream signaling events. These observations have led to the suggestion that in addition to lysosomal dysfunction produced by SM accumulation, part of the pathogenesis of NPA and NPB is related to alterations in signaling pathways at the plasma membrane.
A process that forms myelin-like layered structures This process is dependent on the course of phospholipidosis.
lamellar body formation in lysosome [Phospholipidosis]
myelin figureformation in lysosome [Phospholipidosis]
ASPA relates to myelination in the CNS, but not observed in the liver.
Removing ceramide by Kupffer cell or macrophage is a subtype of removing: A process that takes ceramide from a cell by Kupffer cells or macrophages .
Removing ceramide by Kupffer cell or macrophage
Hyperfunction of ceramide phagocytosis by Kupffer cell or macrophage is a subtype of hyperfunctioning: A process that performs an excessive ceramide phagocytosis by Kupffer cells or macrophages.
hyperfunction of ceramide phagocytosis by Kupffer cell or macrophage
Acid ceramidase inactivation is a subtype of molecular inactivation: A process that changes the activity of the acid ceramidase to be lower.
Acid ceramidase inactivation is a subtype of molecular inactivation: A process that changes the activity of the acid ceramidase to be lower. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis.
acid ceramidase inactivation [Phospholipidosis]
Increasing number of macrophage derived foam cell is a subtype of increasing number of objects: A process that becomes larger in the number of foam cell, a type of macrophage containing lipids in small vacuoles, in the liver. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis(severe).
increasing number of macrophage derived foam cell [Phospholipidosis(severe)]
Phospholipid homeostasis imbalance is a subtype of lipid homeostasis imbalance: A process that becomes lacking a phospholipid homeostastasis balance. And the degree is mild. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (mild).
phospholipid homeostasis imbalance [Phospholipidosis (mild) ]
Dysfunction of sphingomyelin degradation is a subtype of dysfunction of phosphosphingolipid degradation: A process that performs an abnormal and incomplete sphingomyelin degradation. This process can constitute the course of Phospholipidosis.
dysfunction of sphingomyelin degradation [Phospholipidosis-sphingomyelin disorder]
The totality of all processes through which the sphingomyelin disorder is realized.
sphingomyelin disorder (phospholipidosis)
Lysosomal cholesterol storage is a subtype of cholesterol storage: A process that keeps cholesterol in the lysosome moderately. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis(moderate).
lysosomal cholesterol storage (moderate)[Phospholipidosis]
Sphingomyelin homeostasis imbalance is a subtype of phospholipid homeostasis imbalance: A process that becomes lacking asphingomyelin homeostastasis balance. This process is dependent on the genetic and can constitute the course of Phospholipidosis (sphingomyelin disorder.
sphingomyelin homeostasis imbalance [Phospholipidosis - sphingomyelin disorder]
Any process that increases the rate, frequency or extent of macrophage derived foam cell differentiation. Macrophage derived foam cell differentiation is the process in which a macrophage acquires the specialized features of a foam cell. A foam cell is a type of cell containing lipids in small vacuoles and typically seen in atherosclerotic lesions, as well as other conditions. This entity is a specific course-dependent process. This process can constitute the course of sphingomyelin disorder.
positive regulation of macrophage derived foam cell differentiation [sphingomyelin disorder]
Increasing number of macrophage derived foam cell is a subtype of increasing number of objects: A process that becomes larger in the number of foam cell, a type of macrophage containing lipids in small vacuoles, in the liver. This entity is a specific course-dependent process. This process can constitute the course of sphingomyelin disorder.
increasing number of macrophage derived foam cell [Phospholipidosis(sphingomyelin disorder )]
Dysfunction of sphingomyelin degradation is a subtype of hypofunction of decomposing: A process that performs a decreased or insufficient sphingomyelin degradation. This process can constitute the course of sphingomyelin disorder.
hypofunction of sphingomyelin degradation [Phospholipidosis-sphingomyelin disorder]
A process that becomes lacking a homeostastasis balance of the sphingomyelin metabolism. This process is dependent on the sphingomyelin disorder and can constitute the course of Phospholipidosis.
sphingomyelin metabolism imbalance [Phospholipidosis ]
SLC38A4 (predicted)(human) [mitochondrial damage]
BCL2A1 (predicted)(human) [mitochondrial damage]
TRIM55 (predicted)(human) [mitochondrial damage]
CYP1A1 (predicted)(human) [mitochondrial damage]
PIM3 (predicted)(human) [mitochondrial damage]
GFRA1 (predicted)(human) [mitochondrial damage]
ATAD2 (predicted)(human) [mitochondrial damage]
C9orf72 (predicted)(human) [mitochondrial damage]
FEN1 (predicted)(human) [mitochondrial damage]
SKA2 (predicted)(human) [mitochondrial damage]
TSKU (predicted)(human) [mitochondrial damage]
SEL1L (predicted)(human) [mitochondrial damage]
PCK1 (predicted)(human) [mitochondrial damage]
Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver. Second, loss of anaplerosis/cataplerosis via genetic knockdown of phosphoenolpyruvate carboxykinase 1 (Pck1) prevented fatty acid-induced rise in oxidative flux, oxidative stress, and inflammation.
Collectively, these data suggest that enforced PCK1 expression triggers glucose-deprived liver cancer cell death by causing truncated gluconeogenesis, energy crisis, TCA cycle cataplerosis and high ROS levels. Supporting this notion, PCK1 expression in SK-Hep-1 dramatically reduced cellular ATP level by 4 folds in cells cultured in low glucose medium, but not in normal medium (Fig. 4c).
NEAT1 (predicted)(human) [mitochondrial damage]
SRPX2 (predicted)(human) [mitochondrial damage]
TMPO (predicted)(human) [mitochondrial damage]
SLC3A1 (predicted)(human) [mitochondrial damage]
RHNO1 (predicted)(human) [mitochondrial damage]
ORC6 (predicted)(human) [mitochondrial damage]
CDCA5 (predicted)(human) [mitochondrial damage]
UBE2T (predicted)(human) [mitochondrial damage]
Liver cancer dependent molecule is a subtype of toxic course dependent chemical entity. This gene can participate in the course of Liver cancer as a gene product. Gene profile:Human/in vitro/Hepatocyte/
liver cancer dependent molecule (human in vitro)
Overall, we concluded that HULC functions as an oncogene in hepatoma cells, acting mechanistically by deregulating lipid metabolism through a signaling pathway involving miR-9, PPARA, and ACSL1 that is reinforced by a feed-forward pathway involving cholesterol and RXRA to drive HULC signaling.
PTPRD (predicted)(human) [hepatocarcinogenesis]
SCAPER (predicted)(human) [hepatocarcinogenesis]
GPHN (predicted)(human) [hepatocarcinogenesis]
Our results show that gephyrin was reduced in LUAD and LUSC, and its low expression in LUSC patients indicated poor prognosis. Conversely, knockdown of gephyrin promoted LUSC cell growth.
ACSM2A (predicted)(human) [hepatocarcinogenesis]
ACSM2B (predicted)(human) [hepatocarcinogenesis]
SPTLC3 (predicted)(human) [hepatocarcinogenesis]
DPYD (predicted)(human) [hepatocarcinogenesis]
In this study, we demonstrated that expression of dihydropyrimidine dehydrogenase (DPYD), a pyrimidine catabolic enzyme, was dose-dependently downregulated by IFN-α in HCC tissues from nude mice. Moreover, upregulation of DPYD in HCC cells could promote in vitro migration, invasion, and in vivo lung metastasis, and inducing changes characteristic of epithelial-mesenchymal transition (EMT). Mechanistically, DPYD functioned as a positive regulator of EMT in HCC by targeting the p38/NF-κB/Snail1 pathway.
KIAA0101 (predicted)(human) [hepatocarcinogenesis]
NS5ATP9 Promotes Beclin 1-Dependent Starvation-Induced Autophagy of Hepatoblastoma Cells. Furthermore, NS5ATP9-mediated autophagy is required for promotion of tumour cell growth, and this effect could be inhibited with 3-methyladenine, chloroquine or by Beclin 1-silencing.
HILPDA (predicted)(human) [hepatocarcinogenesis]
Long Non-Coding RNA PVT1/miR-150/ HIG2 Axis Regulates the Proliferation, Invasion and the Balance of Iron Metabolism of Hepatocellular Carcinoma. Hypoxia-inducible protein 2 (HIG2) was found to be one target gene of miR-150, and PVT1 knockdown could inhibit the expression of HIG2 through up-regulating miR-150 expression. Taken together, these results suggest that PVT1 may effect IRE/IRP regulatory system and cellular iron uptake by regulating miR-150/HIG2 axis.
AGGF1 (predicted)(human) [hepatocarcinogenesis]
AGGF1 expression was significantly correlated with tumoral VEGF expression and CD34-positive microvessel density. Taken together, increased AGGF1 expression is associated with tumor angiogenesis and serves as an independent unfavorable prognostic factor for OS and DFS in HCC.
Together, present study revealed OR3A4 as a novel prognostic target for HCC, which regulated tumor progression and angiogenesis through AGGF1/akt/mTOR pathway.
CLMN (predicted)(human) [hepatocarcinogenesis]
RPS29 (predicted)(human) [hepatocarcinogenesis]
CXCL8 (predicted)(human) [hepatocarcinogenesis]
We showed that CXCL8 secreted by tumor cells at the invasion front were able to promote migration through angiogenesis by upregulating VEGFA and invasion via the AKT/GSK3β/β-catenin/MMP7 pathway by upregulating BCL-2 confirming the key role of CXCL8 during tumor progression.
Silencing PHB1 increased c-Jun N-terminal kinase (JNK) and NF-κB activity, induced nuclear accumulation of c-JUN and p65, and enhanced their binding to the IL-8 promoter containing AP-1 and NF-κB elements. Conditioned medium from PHB1-silenced HepG2 cells increased migration and invasion of parental HepG2 and SK-hep-1 cells, and this was blocked by co-treatment with neutralizing IL-8 antibody. In summary, our findings show that reduced PHB1 expression induces IL-8 transcription by activating NF-κB and AP-1, resulting in enhanced IL-8 expression and release to promote tumorigenesis.
ZNF385B (predicted)(human) [hepatocarcinogenesis]
PMAIP1 (predicted)(human) [hepatocarcinogenesis]
UGT2A3 (predicted)(human) [hepatocarcinogenesis]
CYP1A2 (predicted)(human) [hepatocarcinogenesis]
Collectively, CYP1A2 metabolizes E2 to generate the potent anti-tumor agent 2-ME in HCC. The reduction of CYP1A2 significantly disrupts this metabolic pathway, contributing the progression and growth of HCC and the gender disparity of this malignancy.
UHRF1 (predicted)(human) [hepatocarcinogenesis]
Furthermore, inhibition of proliferation, migration, invasion, and epithelial-mesenchymal transition progression were observed in vitro and in vivo after UHRF1 knockdown, moreover, G2/M arrest was detected in HCC cells.
Downregulation of UHRF1 increases tumor malignancy by activating the CXCR4/AKT-JNK/IL-6/Snail signaling axis in hepatocellular carcinoma cells. In this study, we observed that hypoxia-induced downregulation of UHRF1 contributes to the induction of the epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma cells.
TMEM139 (predicted)(human) [hepatocarcinogenesis]
TTC39A (predicted)(human) [hepatocarcinogenesis]
TMEM150C (predicted)(human) [hepatocarcinogenesis]
Lipid metabolism imbalance is a subtype of imbalance: A process that becomes lacking a homeostastasis balance of lipid metabolism. The degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Alcoholic fatty liver.
lipid metabolism imbalance (severe) [Alcoholic fatty liver]
The deree level is a subtype of qualitative value. The extent or measure of the condition/action.
Lipid homeostasis imbalance is a subtype of chemical homeostasis imbalance: A process that becomes lacking a lipid homeostastasis balance. The degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Alcoholic fatty liver.
lipid homeostasis imbalance (severe) [Alcoholic fatty liver]
Lipid accumulation in hepatocyte (severe) is a subtype of lipid strorage in hepatocyte: A process that keeps lipids in hepatocytes. And the degree is severe. This entity is a specific course-dependent process. This process can constitute the course of Alcoholic fatty liver.
lipid accumulation in hepatocyte (severe) [Alcoholic fatty liver]
An attribute of the finding of bodily harm due to the poisonous effects of something.
Any process that stops, prevents, or reduces the frequency, rate or extent of protein-containing complex assembly.
down regulation of protein-containing complex assembly
down-regulation of protein-containing complex assembly
downregulation of protein-containing complex assembly
inhibition of protein-containing complex assembly
negative regulation of protein-containing complex assembly
Any process that stops, prevents, or reduces the frequency, rate or extent of mitochondrial respiratory chain complex assembly.
negative regulation of mitochondrial respiratory chain complex assembly
Any process that stops, prevents, or reduces the frequency, rate or extent of mitochondrial respiratory chain complex I assembly.
negative regulation of mitochondrial respiratory chain complex I assembly
Any process that stops, prevents, or reduces the frequency, rate or extent of mitochondrial respiratory chain complex II assembly.
negative regulation of mitochondrial respiratory chain complex II assembly
Any process that stops, prevents, or reduces the frequency, rate or extent of mitochondrial respiratory chain complex III assembly.
negative regulation of mitochondrial respiratory chain complex III assembly
Any process that stops, prevents, or reduces the frequency, rate or extent of mitochondrial respiratory chain complex IV assembly.
negative regulation of mitochondrial respiratory chain complex IV assembly
A pathologic process that involves the transformation of normal cells to a neoplastic state and resulting in polyclonal or monoclonal neoplastic cell proliferation. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
Tumor-Associated Macrophages Produce Interleukin 6 and Signal via STAT3 to Promote Expansion of Human Hepatocellular Carcinoma Stem Cells TAMs produce IL6, which promotes expansion of these CSCs and tumorigenesis. Levels of IL6 in human HCC samples correlate with tumor stage and markers of CSCs. We have identified that STAT3 signaling in HCC cells following TAM interaction is critical to increased CSC expansion and increased tumor growth.
Our data demonstrated that increased mitochondrial fission induced release of mtDNA into the cytosol in HCC cells, which is commonly recognized as cytosolic mtDNA stress, suggesting a potentially critical role of mitochondrial fission-regulated mtDNA hemostasis in hepatocarcinogenesis. CCL2 is a multifunctional factor involved in various aspects of liver disease pathogenesis, including cirrhosis and hepatocarcinogenesis. Previous studies have shown that CCL2 promotes the accumulation and polarization of macrophages by CCR2 receptor signaling pathway. Our study demonstrated that CCL2 was a critical mediator to link the cytosolic mtDNA stress in HCC cells and TAM infiltration.
Furthermore, Tnf-α and fibrotic mediators such as type 1 collagen 1 alpha 1 (Col1a1) and alpha smooth muscle actin (Acta2) were upregulated in the livers of GDF15 KO mice treated with CCl4 (Fig. 4d). These data demonstrate that GDF15 deficiency induces hepatic inflammation and fibrosis in the CCl4-induced model of liver fibrosis.
In addition, collagen deposition was significantly increased in the livers of GDF15 KO mice treated with CCl4 (Fig. 4c). Furthermore, Tnf-α and fibrotic mediators such as type 1 collagen 1 alpha 1 (Col1a1) and alpha smooth muscle actin (Acta2) were upregulated in the livers of GDF15 KO mice treated with CCl4 (Fig. 4d). These data demonstrate that GDF15 deficiency induces hepatic inflammation and fibrosis in the CCl4-induced model of liver fibrosis.
Treatment with alcohol also increased the levels of secreted GDF15 in supernatants of cultured hepatocytes. We next investigated the effect of mitochondrial dysfunction on GDF15 expression in hepatocytes. Inhibition of the mitochondrial OXPHOS complex using oligomycin or rotenone significantly increased Gdf15 expression and GDF15 secretion by cultured hepatocytes. Hepatic Gdf15 expression and serum levels of GDF15 were remarkably increased in alcohol-fed mice. Liver-infiltrating monocytes and neutrophils were also increased in the GDF15 KO mice during liver fibrogenesis. These changes in hepatic immune cells were associated with increased tissue inflammation and fibrosis. As shown in Fig. 3c, H&E staining and Oil Red O staining showed that hepatic fat accumulation and immune cell infiltration were increased in alcohol-fed GDF15 KO mice compared to controls (Fig. 3c). In addition, collagen deposition was significantly increased in the livers of GDF15 KO mice treated with CCl4 (Fig. 4c). Furthermore, Tnf-α and fibrotic mediators such as type 1 collagen 1 alpha 1 (Col1a1) and alpha smooth muscle actin (Acta2) were upregulated in the livers of GDF15 KO mice treated with CCl4 (Fig. 4d). These data demonstrate that GDF15 deficiency induces hepatic inflammation and fibrosis in the CCl4-induced model of liver fibrosis.
GDF15 - inactive form (mouse)[mitochondrial disorder]
Treatment with alcohol also increased the levels of secreted GDF15 in supernatants of cultured hepatocytes. We next investigated the effect of mitochondrial dysfunction on GDF15 expression in hepatocytes. Inhibition of the mitochondrial OXPHOS complex using oligomycin or rotenone significantly increased Gdf15 expression and GDF15 secretion by cultured hepatocytes. Hepatic Gdf15 expression and serum levels of GDF15 were remarkably increased in alcohol-fed mice (Fig. 1j–l). Liver-infiltrating monocytes and neutrophils were also increased in the GDF15 KO mice during liver fibrogenesis. These changes in hepatic immune cells were associated with increased tissue inflammation and fibrosis. As shown in Fig. 3c, H&E staining and Oil Red O staining showed that hepatic fat accumulation and immune cell infiltration were increased in alcohol-fed GDF15 KO mice compared to controls (Fig. 3c). In addition, collagen deposition was significantly increased in the livers of GDF15 KO mice treated with CCl4 (Fig. 4c). Furthermore, Tnf-α and fibrotic mediators such as type 1 collagen 1 alpha 1 (Col1a1) and alpha smooth muscle actin (Acta2) were upregulated in the livers of GDF15 KO mice treated with CCl4 (Fig. 4d). These data demonstrate that GDF15 deficiency induces hepatic inflammation and fibrosis in the CCl4-induced model of liver fibrosis.
Any process that stops, prevents, or reduces the frequency, rate or extent of mitochondrial respiratory chain complex assembly. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
Negative regulation of respiratory complex proteins synthesis
Finally, higher FOXO1 activity and oxidative stress could be involved, by way of impaired mitochondrial biogenesis. Indeed, FoxO1 activation is able to reduce the content of different MRC polypeptides, possibly by decreasing heme synthesis and impairing PGC1α activity. Reduced PGC1α activity could also be secondary to oxidative stress and inflammation, as previously mentioned (Fig. 4).
Moreover, in vitro treatment of liver cells with saturated fatty acids (palmitic and stearic acids) reproduces mitochondrial dysfunction found in NASH, including decreasing cellular ATP content and mtDNA-encoded oxidative phosphorylation (OXPHOS) subunit expression, coupled with increased oxidative stress.
Mitochondrial damage dependent molecule is a subtype of toxic course dependent chemical entity. This gene can participate in the course of Mitochondrial damage as a gene product. Gene profile:Mouse
mitochondrial damage dependent molecule (mouse)
CYP2E1 (canonical)[mitochondrial disorder]
A second mechanism is ROS generation due to CYP2E1 overexpression and reduced levels of mtGSH. Whereas CYP2E1 induction could be secondary to higher levels of glucagon, FAs and KBs, reduced mtGSH could result from higher mitochondrial levels of cholesterol.
Moreover, the radicals produced by cytochrome P450 2E1-mediated CCl4 metabolism bind to mtDNA directly and also promote lipid peroxidation, which results in degradation of mtDNA.
Furthermore, NF-kB, JNK, and p38 signaling pathways, which are closely associated with hepatic inflammation and fibrosis, were inhibited by treatment with rGDF15 in a mouse model of liver fibrosis (Fig. 6).
In addition, there is more pronounced WAT remodeling with more adipose tissue-associated macrophages infiltration, more M1 macrophage polarization and thus an elevated inflammatory response. Mechanistically, hyperactivation of MAPK/JNK leads to insulin insensitivity, which can be inhibited by knocking out Mapk8/Jnk1 in fundc1 KO mice.
Mitochondrial-derived ROS activate mitogen-activated protein kinases (MAPKs) including c-Jun N-terminal kinase (JNK). Phosphorylated JNK translocates to the mitochondria, where it binds to scaffold proteins inhibiting the mitochondrial respiratory chain and further increasing ROS production. Gan et al. showed that mitochondrial-free cholesterol deposition causes hepatocyte apoptosis and necrosis through c-Jun N-terminal kinase (JNK) activation, associated with increased high-mobility group box 1 (HMGB1), and cytolytic effects on neighboring hepatocytes driven by Toll-like receptor 4 (TLR4). Hepatocyte free cholesterol lipotoxicity results from JNK1-mediated mitochondrial injury and is HMGB1 and TLR4-dependent.
They have also demonstrated that impaired mitophagy can promote macrophage infiltration to activate MAPK signal pathway and inflammatory response to impair mitochondrial quality control, subsequently causing insulin resistance and hepatic steatosis.
Drp1-mediated mitochondrial fission induced the cytosolic mtDNA stress to enhance the CCL2 secretion from HCC cells by TLR9-mediated NF-κB signaling pathway, and thus promoted the TAM recruitment and polarization. Tumor-associated macrophages (TAMs) contribute to hepatocellular carcinoma (HCC) progression.
NEAT1 (predicted) - inactive form (human) [mitochondrial damage]
Drp1-mediated mitochondrial fission induced the cytosolic mtDNA stress to enhance the CCL2 secretion from HCC cells by TLR9-mediated NF-κB signaling pathway, and thus promoted the TAM recruitment and polarization.
Mitochondrial DAMPs (MTDs) activate pattern recognition receptors (PRRs), such as Toll-like receptor (TLR)9. After binding to TLR9, mitochondrial DAMPs trigger numerous downstream pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), the nucleotide binding oligomerization domain (NOD)-like receptor family, pyrin domain containing 3 (NLRP3), and interferon regulatory factor-dependent type 1 to promote inflammation.
A protein complex consisting of cyclin B1 and cyclin-dependent kinase 1 (CDK1). Cyclins are characterized by periodicity in protein abundance throughout the cell cycle. Cyclin-dependent kinases represent a family of serine/threonine protein kinases that become active upon binding to a cyclin regulatory partner.
cyclin B1-CDK1 complex (human) [mitochondrial disorder]
cyclin B1-CDK1 complex - inactive form (canonical)[mitochondrial disorder]
cyclin B1-CDK1 complex inactivation is a subtype of molecular inactivation: A process that changes the activity of the cyclin B1-CDK1 complex to be lower.
cyclin B1-CDK1 complex inactivation is a subtype of molecular inactivation: A process that changes the activity of the cyclin B1-CDK1 complex to be lower. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
cyclin B1-CDK1 complex inactivation [mitochondrial disorder]
ACTA2 production is a subtype of Actin production: A process that makes existent of ACTA2 due to biosynthesis, secretion, or membrane trafficking, resulting in an increase in its levels. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
ACTA2 production [mitochondrial disorder]
The appearance of chemokine (C-C motif) ligand 2 due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
CCL2 production [mitochondrial disorder]
Process of binding by which free radicals interact with DNA (deoxyribonucleic acid).
COL1A1 production is a subtype of collagen production: A process that makes existent of a ollagen due to biosynthesis, secretion, or membrane trafficking, resulting in an increase in its levels. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
COL1A1 production [mitochondrial disorder]
Negative regulation of cell cycle G2/M phase transition is a subtype of negative regulation of cell cycle: Any process that stops, prevents or reduces the frequency, rate or extent of cell cycle G2/M phase transition. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
negative regulation of cell cycle G2/M phase transition [mitochondrial disorder]
GDF15 inactivation is a subtype of molecular inactivation: A process that changes the activity of the GDF15 (Growth differentiation factor 15) to be lower. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
GDF15 inactivation [mitochondrial disorder]
Liver-infiltrating monocytes and neutrophils were also increased in the GDF15 KO mice during liver fibrogenesis. These changes in hepatic immune cells were associated with increased tissue inflammation and fibrosis. As shown in Fig. 3c, H&E staining and Oil Red O staining showed that hepatic fat accumulation and immune cell infiltration were increased in alcohol-fed GDF15 KO mice compared to controls (Fig. 3c). In addition, collagen deposition was significantly increased in the livers of GDF15 KO mice treated with CCl4 (Fig. 4c). Furthermore, Tnf-α and fibrotic mediators such as type 1 collagen 1 alpha 1 (Col1a1) and alpha smooth muscle actin (Acta2) were upregulated in the livers of GDF15 KO mice treated with CCl4 (Fig. 4d). These data demonstrate that GDF15 deficiency induces hepatic inflammation and fibrosis in the CCl4-induced model of liver fibrosis. Furthermore, NF-kB, JNK, and p38 signaling pathways, which are closely associated with hepatic inflammation and fibrosis, were inhibited by treatment with rGDF15 in a mouse model of liver fibrosis (Fig. 6).
GDF15 inactivation is a subtype of molecular inactivation: A process that changes the activity of the GDF15 (Growth differentiation factor 15) to be lower.
JNK signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the JNK (a stress-activated protein kinase (SAPK) ). This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
JNK signaling (primitive) [mitochondrial disorder]
NEAT1 inactivation is a subtype of molecular inactivation: A process that changes the activity of the NEAT1 (nuclear paraspeckle assembly transcript 1) to be lower. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
NEAT1 inactivation [mitochondrial disorder]
Strikingly, NEAT1-depleted single cell clones showed a consis- tent reduction in mitochondrial DNA (mtDNA) (Fig. 7a), reduced mitochondrial respiration (by detection of the oxygen consumption rate (OCR); Fig. 7b) and adenosine triphosphate (ATP) production (Fig. 7c), reduced OCR and extracellular acidification rate (ECAR) rate (Fig. 7d), suggesting that the aberrant NEAT1 expression could cause mitochondrial dysfunction.
NfkB signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transduced with the regulation of transcription of target genes by NF-kappaB. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
NfkB signaling (primitive) [Mitochondrial disorder]
After binding to TLR9, mitochondrial DAMPs trigger numerous downstream pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), the nucleotide binding oligomerization domain (NOD)-like receptor family, pyrin domain containing 3 (NLRP3), and interferon regulatory factor-dependent type 1 to promote inflammation.
p38 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the p38 (a Mitogen-Activated Protein Kinase). This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
p38 signaling (primitive) [mitochondrial disorder]
TLR9 signaling is a subtype of signaling [biological]: Any series of molecular signals generated as a consequence of binding to toll-like receptor 9. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
The appearance of tumor necrosis factor due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
tumor necrosis factor production [mitochondrial disorder]
NAFLD has been associated with higher hepatic expression of the inducible nitric oxide (NO) synthase (iNOS), mainly as a consequence of tumor necrosis factor‐α (TNF‐α) overproduction by the Kupffer cells. NO can readily react with the superoxide anion, thus generating the RNS peroxynitrite, which has deleterious effects on mitochondrial function and genome. TNF‐α is able to impair MRC activity, possibly by inducing hypoxia inducible factor‐1α (HIF‐1α) and mtDNA damage.
TNF-α induces mitochondrial perturbations such as swelling with a lighter matrix and abnormal morphological alterations in the membrane.
Mitochondrial ROS (mtROS) and lipid peroxidation also trigger proinflammatory cytokines such as interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1 beta (IL-1β), which are critical mediators of inflammation in NASH.
A moving process of alcohol from the outside to the inside of a body. This entity is a specific course dependent process. This process can constitute the course of mitochondrial disorder.
NO and other RNS are increased in response to chronic alcohol consumption through induction of iNOS.
Chronic alcohol consumption alters mitochondrial oxidative phosphorylation in the liver by suppressing the synthesis of respiratory complex proteins. Alcohol-mediated damage of mitochondrial DNA (mtDNA) also impairs cellular energy metabolism via enhanced formation of reactive oxygen species (ROS). GDF15 is essential for the regulation of alcohol-mediated liver injury and steatosis.
The appearance of interleukin-6 due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
interleukin-6 production [mitochondrial disorder]
mtFAO in liver could be favored by increased levels of hormones and other circulating factors such as leptin, FGF21, and interleukin 6 (IL6).
Process of binding by which radicals interact with mtDNA (mitochondrial deoxyribonucleic acid). This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
binding to mtDNA by radicals [mitochondrial disorder]]
Increasing free radical is a subtype of increasing quantity: A process that changes the amount of free radicals to be larger. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
increasing free radical [mitochondrial disorder]
The process that results in the movement of mitochondriall DNA from the mitochondria. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
release of DNA from mitochondria [mitochondria disorder]
Decreasing mtDNA level is a subtype of decreasing quantity: A process that changes the amount of glycogen level to be lower. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
decreasing mtDNA level [mitochondrial disorder]
Both tamoxifen and tacrine reduce mtDNA synthesis by interacting with the mitochondrial topoisomerases.
Fourthly, drugs can impair mitochondrial FAO and induce microvesicular steatosis by reducing mtDNA levels (Table 1). Indeed, profound mtDNA depletion induces MRC impairment and secondary inhibition of FAO. This has been shown for the antiviral fialuridine (FIAU), AZT, d4T, and ddI, which all inhibit the mtDNA polymerase γ.
MtDNA depletion in hepatocytes impairs mitochondrial function and causes hepatic steatosis and other liver injury. Reduced levels of mtDNA have also been reported in patients with NASH that seem to be responsible for the impairment of mitochondrial function and development and progression of liver steatosis and other liver injuries. Reduced expression of mtDNA-encoded polypeptides has been reported in patients with NASH, further supporting a role for mtDNA depletion in mitochondrial dysfunction.
The division of a mitochondrion within a cell to form two or more separate mitochondrial compartments. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
mitochondria fission [Mitochondrial disorder]
Fission permits distribution of mitochondria throughout a cell (e.g., transport down axons or to permit allocation prior to cell division), and facilitates apoptosis via release of cytochrome C under some circumstances (Mishra and Chan 2014). High-level exposures may result in increased fission, which blocks efficient ATP generation and limits rates of functional complementation, in addition to potentially leading to apoptosis.
In the present study, our data demonstrated that increased mitochondrial fission induced release of mtDNA into the cytosol in HCC cells, which is commonly recognized as cytosolic mtDNA stress, suggesting a potentially critical role of mitochondrial fission-regulated mtDNA hemostasis in hepatocarcinogenesis. Drp1-mediated mitochondrial fission induced the cytosolic mtDNA stress to enhance the CCL2 secretion from HCC cells by TLR9-mediated NF-κB signaling pathway, and thus promoted the TAM recruitment and polarization.
The chemical reactions and pathways resulting in the breakdown of mitochondrial DNA. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
mitochondrial DNA catabolic process [mitochondrial disorder]
The process that results in the movement of cytochrome c from the mitochondrial intermembrane space into the cytosol, which is part of the apoptotic signaling pathway and leads to caspase activation. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
release of cytochrome c from mitochondria [mitochondrial disorder]
Mitochondrial dysfunction results in the release of several proapoptotic proteins into the cytosol, including cytochrome c. Cardiolipin has been shown to be involved in several steps of the intrinsic pathway of the apoptotic process, including mitochondrial permeability transition pore (MPTP) and cytochrome c release from mitochondria. Another consequence of cytochrome c release from mitochondria is that it interferes with electron transport through ETC, resulting in ROS formation and triggering a new vicious cycle, which will worsen the disturbance.
Fission permits distribution of mitochondria throughout a cell (e.g., transport down axons or to permit allocation prior to cell division), and facilitates apoptosis via release of cytochrome C under some circumstances (Mishra and Chan 2014).
Energy metabolic dysfunction is a subtype of Metabolic dysfunctioning: A process that performs an abnormal and incomplete energy metabolic function. This entity is a specific course-dependent process. This process can constitute the Mitochondrial disorder.
metabolic dysfunction of precursor metabolites and energy generation [mitochondrial disorder]
Experimental investigations also pointed to a progressive reduction of MRC activity during NAFLD, which could impair energy output and aggravate ROS overproduction by the damaged MRC.
Any process that stops, prevents, or reduces the frequency, rate or extent of mitochondrial respiratory chain complex IV assembly. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
Negative regulation of respiratory complex IV proteins synthesis [mitochondrial disorder]
Additionally, carbon tetrachloride (CCl4) reduces mitochondrial respiratory chain complex IV activity and depletes mtDNA in the liver.
The orderly movement of a monocyte from one site to another. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
monocyte migration [mitochondrial disorder]
Liver-infiltrating monocytes and neutrophils were also increased in the GDF15 KO mice during liver fibrogenesis. These changes in hepatic immune cells were associated with increased tissue inflammation and fibrosis.
Increasing uptake amount of mitochondrial calcium ion is a subtype of increasing quantity: A process that changes the uptake amount of mitochondrial calcium ion to be higher. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
increasing uptake amount of mitochondrial calcium ion [Mitochondrial disorder]
The orderly movement of a neutrophil from one site to another. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
neutrophil migration [mitochondrial disorder]
The synthesis or release of a cytokine following a inflammatory stimulus as part of an inflammatory response, resulting in an increase in its intracellular or extracellular levels. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
cytokine production involved in inflammatory response [mitochondrial disorder]
Oxidative stress may cause damage at cellular level, such as membrane lipid peroxidation, cell degeneration and necrosis, cell death by apoptosis, proinflammatory cytokine expression, liver stellate cell activation and fibrogenesis.
GDF15 may regulate the hepatic immune microenvironment by inhibiting pro-inflammatory cytokine production from liver-resident macrophages.
Inflammatory cytokine gene expression is a subtype of gene expression: The process in which a gene sequence is converted into a mature inflammatory cytokine gene product or products (proteins or RNA). This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
inflammatory cytokine gene expression [mitochondrial disorder]
Inflammatory response is a subtype of changing material: The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Inflammatory response [mitochondrial disorder]
Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver. Second, loss of anaplerosis/cataplerosis via genetic knockdown of phosphoenolpyruvate carboxykinase 1 (Pck1) prevented fatty acid-induced rise in oxidative flux, oxidative stress, and inflammation. Figure 8 Histological data support a role for oxidative metabolism in NAFLD in humans.
Emerging evidence suggests that mitochondrial dysfunction or maladaptation contributes to detrimental effects on hepatocyte bioenergetics, reactive oxygen species (ROS) homeostasis, endoplasmic reticulum (ER) stress, inflammation, and cell death leading to NASH and HCC. Saturated fats promote fatty liver and accumulation of lipotoxic byproducts including ceramides and diacylglycerols is associated with hepatic inflammation and mitochondrial ROS production resulting in liver cell death.
lipotoxicity and inflammation can interfere with insulin signaling pathway to cause hepatic insulin resistance;
Cellular damage is a subtype of damaging: A process that injuries the structure of the cell as the direct or indirect result of an external force. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
cellular damage [mitochondrial disorder]
Moreover, TNF-α and IL-6 promote iron accumulation, which further fuels oxidative stress-driven cell toxicity and can activate fibrogenesis and carcinogenesis in metabolic syndrome.
Tumor-associated macrophage (TAM) activation is a subtype of macrophage activation: A change in morphology and behavior of TAMs resulting from exposure to a cytokine, chemokine, cellular ligand, or soluble factor. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
Tumor-associated macrophage activation[Mitochondrial disorder]
Tumor-associated macrophages (TAMs) contribute to hepatocellular carcinoma (HCC) progression. Drp1-mediated mitochondrial fission induced the cytosolic mtDNA stress to enhance the CCL2 secretion from HCC cells by TLR9-mediated NF-κB signaling pathway, and thus promoted the TAM recruitment and polarization.
The orderly movement of a TAM macrophage from one site to another. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
tumor-associated macrophage migration [mitochondrial disorder]
The orderly movement of a TAM macrophage from one site to another.
Tumor-associated macrophage (TAM) activation is a subtype of macrophage activation: A change in morphology and behavior of TAMs resulting from exposure to a cytokine, chemokine, cellular ligand, or soluble factor. This entity is a specific course-dependent process. This process can constitute the course of Hepatocarcinogenesis.
Tumor-associated macrophage activation@hepatocarcinogenesis
Tumor-Associated Macrophages Produce Interleukin 6 and Signal via STAT3 to Promote Expansion of Human Hepatocellular Carcinoma Stem Cells. We have identified that STAT3 signaling in HCC cells following TAM interaction is critical to increased CSC expansion and increased tumor growth.
Tumor-associated macrophages (TAMs) contribute to hepatocellular carcinoma (HCC) progression. Drp1-mediated mitochondrial fission induced the cytosolic mtDNA stress to enhance the CCL2 secretion from HCC cells by TLR9-mediated NF-κB signaling pathway, and thus promoted the TAM recruitment and polarization. Previous studies have shown that CCL2 promotes the accumulation and polarization of macrophages by CCR2 receptor signaling pathway. Our study demonstrated that CCL2 was a critical mediator to link the cytosolic mtDNA stress in HCC cells and TAM infiltration.
On the one hand, intratumoral interleukins, such as IL-1β and IL-6, are correlated with the number of proinflammatory tumor-associated macrophages.
Tumor-associated macrophage (TAM) activation is a subtype of macrophage activation: A change in morphology and behavior of TAMs resulting from exposure to a cytokine, chemokine, cellular ligand, or soluble factor.
Tumor-associated macrophage polarization
Lipoperoxidation is a subtype of lipid oxidation: The degradation of lipids caused by an oxidative attack from free radicals. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
lipoperoxidation [mitochondrial disorder]
Other mechanisms leading to impaired MRC activity could include higher levels of different lipid intermediates including free FAs, increased generation of lipid peroxidation products such as 4‐HNE, and reduced adiponectin action. In addition to ROS, reactive nitrogen species (RNS) and lipid peroxidation products are able to damage mtDNA. Several MRC complexes including COX are sensitive to ROS and RNS. In addition, COX can be inhibited by low levels of NO and inactivated by 4‐hydroxynonenal (4‐HNE), a reactive aldehyde generated during lipid peroxidation.
The imbalance of respiratory complex activity during the development of NAFLD and its progression to NASH leads to increased mitochondrial reactive oxygen species (ROS), causing oxidative mitochondrial DNA (mtDNA) damage, mitochondria structural abnormalities, and lipid peroxidation. Mitochondrial ROS (mtROS) and lipid peroxidation also trigger proinflammatory cytokines such as interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1 beta (IL-1β), which are critical mediators of inflammation in NASH.
Hepatic fibrosis is a subtype of fibrosis: A process that replaces liver tissues to fibrous connective tissues, usually as a consequence of inflammation or other injury. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
hepatic fibrosis [mitochondrial disorder]
Liver-infiltrating monocytes and neutrophils were also increased in the GDF15 KO mice during liver fibrogenesis. These changes in hepatic immune cells were associated with increased tissue inflammation and fibrosis. Recombinant GDF15 attenuates CCl4-induced liver fibrosis by suppressing the hepatic inflammatory response. In addition, collagen deposition was significantly increased in the livers of GDF15 KO mice treated with CCl4 (Fig. 4c). Furthermore, Tnf-α and fibrotic mediators such as type 1 collagen 1 alpha 1 (Col1a1) and alpha smooth muscle actin (Acta2) were upregulated in the livers of GDF15 KO mice treated with CCl4 (Fig. 4d). These data demonstrate that GDF15 deficiency induces hepatic inflammation and fibrosis in the CCl4-induced model of liver fibrosis.
The totality of all processes through which hepatocarcinogenesis is realized.
Liver malfunction is a subtype of organ malfunction: A process that does not perform liver function correctly or not functioning at all. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
liver malfunction [mitochondrial disorder]
MtDNA depletion in hepatocytes impairs mitochondrial function and causes hepatic steatosis and other liver injury.
During nonalcoholic fatty liver disease (NAFLD), mitochondria also produce ROS that damage hepatocytes, trigger inflammation, and contribute to insulin resistance. Figure 8 Histological data support a role for oxidative metabolism in NAFLD in humans.
Scleroprotein production is a subtype of protein production: A process that makes existent of scleroprotein due to biosynthesis, secretion, or membrane trafficking, resulting in an increase in its levels.
Collagen production is a subtype of scleroprotein production: A process that makes existent of collagen due to biosynthesis, secretion, or membrane trafficking, resulting in an increase in its levels.
COL1A1 production is a subtype of collagen production: A process that makes existent of a ollagen due to biosynthesis, secretion, or membrane trafficking, resulting in an increase in its levels.
cytoskeletal protein production is a subtype of protein production: A process that makes existent of cytoskeletal protein due to biosynthesis, secretion, or membrane trafficking, resulting in an increase in its levels.
Actin production is a subtype of cytoskeletal protein production: A process that makes existent of actin due to biosynthesis, secretion, or membrane trafficking, resulting in an increase in its levels.
ACTA2 production is a subtype of Actin production: A process that makes existent of ACTA2 due to biosynthesis, secretion, or membrane trafficking, resulting in an increase in its levels.
The appearance of chemokine (C-C motif) ligand 2 due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels.
chemokine (C-C motif) ligand 2 production
The appearance of chemokine (C-C motif) ligand 2 due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Previous studies have shown that CCL2 promotes the accumulation and polarization of macrophages by CCR2 receptor signaling pathway. Our study demonstrated that CCL2 was a critical mediator to link the cytosolic mtDNA stress in HCC cells and TAM infiltration.
Mitochondrial damage dependent molecule is a subtype of toxic course dependent chemical entity. This gene can participate in the course of Mitochondrial damage as a gene product. Gene profile:caonical that described in textbooks or articles.
mitochondrial damage dependent molecule (canonical)
The chemical reactions and pathways involving carbon tetrachloride, a toxic, carcinogenic compound which is used as a general solvent in industrial degreasing operations. It is also used as grain fumigant and a chemical intermediate in the production of refrigerants.
The chemical reactions and pathways involving carbon tetrachloride, a toxic, carcinogenic compound which is used as a general solvent in industrial degreasing operations. It is also used as grain fumigant and a chemical intermediate in the production of refrigerants. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
carbon tetrachloride metabolic process [mitochondrial disorder]
A role played by the entity which receives DNA and transmits operand(s).
NEAT1 inactivation is a subtype of molecular inactivation: A process that changes the activity of the NEAT1 (nuclear paraspeckle assembly transcript 1) to be lower.
NfkB signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transduced with the regulation of transcription of target genes by NF-kappaB. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
NfkB signaling (primitive) [hepatocarcinogenesis]
Consequently, PROX1 activated nuclear factor κB signaling and selectively promoted expression of the proangiogenic interleukin‐8 (IL‐8) by epigenetically stimulating the IL‐8 promoter.
Mechanistically, DPYD functioned as a positive regulator of EMT in HCC by targeting the p38/NF-κB/Snail1 pathway. Moreover, we also confirmed that the p38/NF-κB/Snail1 signaling by which DPYD regulates EMT and facilitates HCC progression.
Silencing PHB1 increased c-Jun N-terminal kinase (JNK) and NF-κB activity, induced nuclear accumulation of c-JUN and p65, and enhanced their binding to the IL-8 promoter containing AP-1 and NF-κB elements. In summary, our findings show that reduced PHB1 expression induces IL-8 transcription by activating NF-κB and AP-1, resulting in enhanced IL-8 expression and release to promote tumorigenesis.
It exerts an antiapoptotic effect via the Notch-1/NF-κB pathway and interacts with the genes involved in apoptosis, such as Bcl-2, cyclin D1, survivin, and cIAPs (cellular inhibitor of apoptosis).
TLR9 signaling is a subtype of signaling [biological]: Any series of molecular signals generated as a consequence of binding to toll-like receptor 9. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
TLR9 signaling (primitive) is a subtype of TLR signaling [biological]: Any series of molecular signals generated as a consequence of binding to toll-like receptor 9.
TLR signaling (primitive) is a subtype of signaling [biological]: Any series of molecular signals generated as a consequence of binding to toll-like receptor.
An intracellular protein kinase cascade containing at least a p38 MAPK, a MAPKK and a MAP3K. The cascade can also contain an additional tier: the upstream MAP4K. The kinases in each tier phosphorylate and activate the kinases in the downstream tier to transmit a signal within a cell. (by GO)
p38 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the p38 (a Mitogen-Activated Protein Kinase).
The appearance of interleukin-6 due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels.
energy metabolic dysfunction is a subtype of Metabolic dysfunctioning: A process that performs an abnormal and incomplete energy metabolic function.
metabolic dysfunction of precursor metabolites and energy generation
The aggregation of collagen in a particular location in an organism, tissue or cell, occurring in response to some external stimulus.
The aggregation of collagen in a particular location in an organism, tissue or cell, occurring in response to some external stimulus. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
collagen deposition [mitochondrial disorder]
Process of binding by which radicals interact with mtDNA (mitochondrial deoxyribonucleic acid).
The process that results in the movement of mitochondriall DNA from the mitochondria. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
release of DNA from mitochondria [hepatocarcinogenesis]
mtDNA is one major type of damage-associated molecular patterns (DAMPs), which can activate the DNA sensor TLR9 signaling to trigger the inflammatory responses. Tumor-associated macrophages (TAMs) contribute to hepatocellular carcinoma (HCC) progression. Drp1-mediated mitochondrial fission induced the cytosolic mtDNA stress to enhance the CCL2 secretion from HCC cells by TLR9-mediated NF-κB signaling pathway, and thus promoted the TAM recruitment and polarization.
Decreasing mtDNA level is a subtype of decreasing quantity: A process that changes the amount of mtDNA level to be lower.
The division of a mitochondrion within a cell to form two or more separate mitochondrial compartments. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
mitochondrial fission [hepatocarcinogenesis]
In the present study, our data demonstrated that increased mitochondrial fission induced release of mtDNA into the cytosol in HCC cells, which is commonly recognized as cytosolic mtDNA stress, suggesting a potentially critical role of mitochondrial fission-regulated mtDNA hemostasis in hepatocarcinogenesis. Drp1-mediated mitochondrial fission induced the cytosolic mtDNA stress to enhance the CCL2 secretion from HCC cells by TLR9-mediated NF-κB signaling pathway, and thus promoted the TAM recruitment and polarization. Tumor-associated macrophages (TAMs) contribute to hepatocellular carcinoma (HCC) progression.
mitochondrial disorder dependent chemical compound is a subtype of toxic course dependent chemical entity. This entity (drug) can participate in the course of mitochondrial disorder.
mitochondria disorder dependent chemical compound
The orderly movement of a monocyte from one site to another.
A role played by the entity which negative regulates the respiratory chain.
The orderly movement of a neutrophil from one site to another.
Tumor-Associated Macrophages Produce Interleukin 6 and Signal via STAT3 to Promote Expansion of Human Hepatocellular Carcinoma Stem Cells.
An attribute of the finding of bodily injury due to the poisonous effects of drugs.
An attribute of the finding of liver injury due to the poisonous effects of drugs.
From Drug Induced Liver Injury Rank (DILIrank) Dataset. DILIrank consists of 1,036 FDA-approved drugs that are divided into four classes according to their potential for causing drug-induced liver injury (DILI).
IL6 signaling is a subtype of signaling [biological]: Any series of molecular signals generated as a consequence of binding to Interleukin 6. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Numerous studies showed increased expression of PPARα in fatty liver. Different cues such as FAs, leptin, and IL6 could activate PPARα and its target genes involved in mtFAO (CPT1, MCAD), peroxisomal FAO (acyl‐CoA oxidase), and VLDL production (microsomal triglyceride transfer protein). mtFAO in liver could be favored by increased levels of hormones and other circulating factors such as leptin, FGF21, and interleukin 6 (IL6).
Mitochondrial ROS (mtROS) and lipid peroxidation also trigger proinflammatory cytokines such as interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1 beta (IL-1β), which are critical mediators of inflammation in NASH. Moreover, TNF-α and IL-6 promote iron accumulation, which further fuels oxidative stress-driven cell toxicity and can activate fibrogenesis and carcinogenesis in metabolic syndrome.
STAT3 activation is a subtype of molecular activation: A process that changes the activity of the STAT3 to be higher. This entity is a specific course-dependent process. This process can constitute the course of Mitochondrial disorder.
STAT3 activation[Mitochondrial disorder]
STAT3 activation is a subtype of molecular activation: A process that changes the activity of the STAT3 to be higher.
IL-6 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the cytokine IL-6.
mitochondrial respiratory chain complex I subunit
Increasing demand for response to ER stress is a subtype of increasing the demand for response to stress: A process that changes the functional demand for the response to the endoplasmic reticulum (ER) stress to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
increasing demand for response to ER stress [mitochondrial disorder]
cardiolipin peroxidation is a subtype of phospholipid oxidation: The degradation of cardiolipin caused by an oxidative attack from free radicals. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
cardiolipin peroxidation [mitochondrial disorder]
Cardiolipin peroxidation has been associated with mitochondrial dysfunction in multiple tissues in several physiopathological conditions, including NAFLD. Indeed, in mitochondria lacking CL, a respiratory supercomplex formed by complex III and IV is destabilized. Similarly, dimeric organization of ADP/ATP carrier and other ADP/ATP carrier-containing supercomplexes are destabilized in CL-deficient mitochondria. These results suggest that the observed dysfunction of complex I in hepatic mitochondria from CDD animals could be attributed, at least in part, to ROS-induced cardiolipin alterations. Cardiolipin has been shown to be involved in several steps of the intrinsic pathway of the apoptotic process, including mitochondrial permeability transition pore (MPTP) and cytochrome c release from mitochondria. In addition, CL oxidation seems to promote the permeabilization of the outer mitochondrial membrane, probably interacting with Bcl2 family proteins, such as Bax and Bid. Thus, oxidized CL may have a critical role in several steps of the apoptotic process such as: the translocation of t-Bid to mitochondria with subsequent oligomerization of Bax and Bak leading to membrane permeabilization; cytochrome c dissociation from the inner mitochondrial membrane; and activation of MPTP, followed by the release of this hemoprotein from the mitochondrial intermembrane space to the cytosol (Figure ​1).
A type of cell death that is morphologically characterized by an increasingly translucent cytoplasm, swelling of organelles, minor ultrastructural modifications of the nucleus (specifically, dilatation of the nuclear membrane and condensation of chromatin into small, irregular, circumscribed patches) and increased cell volume (oncosis), culminating in the disruption of the plasma membrane and subsequent loss of intracellular contents. Necrotic cells do not fragment into discrete corpses as their apoptotic counterparts do. Moreover, their nuclei remain intact and can aggregate and accumulate in necrotic tissues. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Oxidative stress may cause damage at cellular level, such as membrane lipid peroxidation, cell degeneration and necrosis, cell death by apoptosis, proinflammatory cytokine expression, liver stellate cell activation and fibrogenesis. If MPTP opening is transient, the cell can recover; while in conditions of prolonged MPTP opening and ATP depletion, irreversible damage and cell death occur, predominantly through necrosis.
Reduced mitophagy results in the accumulation of severely damaged mitochondria, leading to cell necrosis releasing mitochondrial damage-associated molecular patterns (DAMPs) that can promote liver inflammation and NASH development. Gan et al. showed that mitochondrial-free cholesterol deposition causes hepatocyte apoptosis and necrosis through c-Jun N-terminal kinase (JNK) activation, associated with increased high-mobility group box 1 (HMGB1), and cytolytic effects on neighboring hepatocytes driven by Toll-like receptor 4 (TLR4).
Cellular membrane lipoperoxidation is a subtype of lipoperoxidation: A process that the degradation of lipids of cellular membrane caused by an oxidative attack from free radicals. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
cellular membrane lipoperoxidation [mitochondrial disorder]
A change in the morphology or behavior of a hepatic stellate cell resulting from exposure to a cytokine, chemokine, hormone, cellular ligand or soluble factor. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
hepatic stellate cell activation [mitochondrial disorder]
mitochondrial membrane morphology changes is a subtype of mitochondria morphology changes: A process that changes the morphology of the mitochondrial membrane. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
mitochondrial membrane morphology changes [mitochondrial disorder]
The appearance of interleukin-1 beta due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
IL-1beta production [mitochondrial disorder]
Insulin resistance (process) is a subtype of decreasing sensitivity: A process that changes the sensitivity to the circulating insulin to be lower. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Insulin resistance (process) [mitochondrial disorder]
Recent studies also show that MAMs are important for hepatic insulin signaling, nutrient sensing, and glucose homeostasis. Therefore, disruption of ER-mitochondria contact sites could exacerbate hepatic lipid accumulation and miscommunication between organelles appears to be related to the pathology of hepatic metabolic diseases.
lipotoxicity and inflammation can interfere with insulin signaling pathway to cause hepatic insulin resistance; In conclusion, mitochondrial dysfunction gives rise to hepatic fatty acid accumulation, which ultimately impairs insulin signal pathway and causes hepatic insulin resistance.
Calcium ion homeostasis imbalance is a subtype of chemical homeostasis imbalance: A process that becomes lacking a calcium ion homeostastasis balance. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Calcium ion homeostasis imbalance [mitochondrial disorder]
Mitochondrial ROS and oxidative stress can disrupt ER function leading to inappropriate release of calcium in liver parenchymal cells.
Hypofunction of sequestering of calcium ion in ER is a subtype of hypofunctioning: A process that performs a decreased or insufficient sequestering of calcium ion in ER. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder..
Hypofunction of sequestering of calcium ion in ER [mitochondrial disorder]
Mitochondrial ROS and oxidative stress can disrupt ER function leading to inappropriate release of calcium in liver parenchymal cells. Moreover, oxidative stress and ROS lead to the release of calcium by the endoplasmic reticulum, further increasing mitochondria ROS production and potentiating proapoptotic pathways.
mitochondria morphology changes is a subtype of changing shape: A process that changes the morphology of the mitochondria. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
mitochondria morphology change [mitochondrial disorder]
In the present study we showed that mutations in TARDBP and C9ORF72 genes, associated to defects in RNA metabolism in ALS and FTD neurodegenerative diseases, affect mitochondria functionality by altering several morphological and bioenergetics parameters in a gene-specific manner. These results suggest that an altered balance of fission and fusion processes may account for the mitochondria morphology changes observed in mTDP-43 and mC9ORF72 fibroblasts.
The imbalance of respiratory complex activity during the development of NAFLD and its progression to NASH leads to increased mitochondrial reactive oxygen species (ROS), causing oxidative mitochondrial DNA (mtDNA) damage, mitochondria structural abnormalities, and lipid peroxidation. Consistent with this, high glucose induces mitochondrial fragmentation, ROS production, loss of mitochondrial membrane potential, and ATP depletion in several rodent and human cell models. More precisely, dietary-induced hypercholesterolemia causes oxidative stress, loss of mitochondrial membrane potential, reduction in ATP content, loss of mitochondrial cristae, and hepatic steatosis in mice.
Any process that results in a change in state of redox. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Mitochondrial-derived ROS also activate AMP-activated protein kinase (AMPK) secondary to redox changes and mitochondrial ATP production. Thus, accumulating evidences suggest that cholesterol overload in mitochondria induces redox imbalances leading to oxidative stress and cell death associated with steatohepatitis.
BAK1(canonical) [mitochondrial disorder]
In addition, CL oxidation seems to promote the permeabilization of the outer mitochondrial membrane, probably interacting with Bcl2 family proteins, such as Bax and Bid. Thus, oxidized CL may have a critical role in several steps of the apoptotic process such as: the translocation of t-Bid to mitochondria with subsequent oligomerization of Bax and Bak leading to membrane permeabilization; cytochrome c dissociation from the inner mitochondrial membrane; and activation of MPTP, followed by the release of this hemoprotein from the mitochondrial intermembrane space to the cytosol (Figure ​1).
Any process that activates or decreases the frequency, rate or extent of mitophagy. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
nagative regulation of mitophagy [mitochondrial disorder]
Damaged mitochondria are usually eliminated by autophagy/mitophagy which is attenuated by lipid accumulation. Prevention of autophagy further leads to accumulation of damaged mitochondria that can release inflammatory DAMPs and cytochrome C to promote cell death, and/or exacerbate endoplasmic reticulum (ER) stress. Reduced mitophagy results in the accumulation of severely damaged mitochondria, leading to cell necrosis releasing mitochondrial damage-associated molecular patterns (DAMPs) that can promote liver inflammation and NASH development.
Wu et al. (2019) have found that impaired mitophagy can accelerate macrophage infiltration in white adipose tissue in high-fat diet–fed mice with FUNDC1 knockout. They have also demonstrated that impaired mitophagy can promote macrophage infiltration to activate MAPK signal pathway and inflammatory response to impair mitochondrial quality control, subsequently causing insulin resistance and hepatic steatosis.
A fatty acid oxidation process that results in the complete beta oxidation of a fatty acid in the mitochondria. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
mitochondrial fatty acid beta-oxidation [mitochondrial disorder]
However, several hormonal and metabolic adaptations are set up in order to restrain hepatic fat accumulation, such as increased mitochondrial fatty acid oxidation (mtFAO). Furthermore, enhanced mtFAO without concomitant up‐regulation of the mitochondrial respiratory chain (MRC) activity induces reactive oxygen species (ROS) overproduction within different MRC components upstream of cytochrome c oxidase.
Hyperfunction of CYP2E1 gene expression is a subtype of hyperfunction of cytochrome 450 gene expression: A process that performs an excesssive gene expression of CYP2E1. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
hyperfunction of CYP2E1 gene expression [mitochondrial disorder]
Hyperfunction of glucose biosynthesis is a subtype of hyperfunction of biosynthesis: A process that performs an excessive glucose biosynthesis. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
hyperfunction of gluconeogenesis [mitochondrial disorder]
Increasing damaged mitochondria is a subtype of decreasing quantity: A process that changes the amount of damaged mitochondria to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Increasing damaged mitochondria [mitochondrial disorder]
Prevention of autophagy further leads to accumulation of damaged mitochondria that can release inflammatory DAMPs and cytochrome C to promote cell death, and/or exacerbate endoplasmic reticulum (ER) stress. Reduced mitophagy results in the accumulation of severely damaged mitochondria, leading to cell necrosis releasing mitochondrial damage-associated molecular patterns (DAMPs) that can promote liver inflammation and NASH development.
Increasing CPT1 level is a subtype of increasing quantity: A process that changes the amount of CPT1 level to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
increasing CPT1 level [mitochondrial disorder]
For instance, LCFA‐mediated PPARα activation increases the expression of the mitochondrial enzymes CPT1 and medium‐chain acyl‐CoA dehydrogenase (MCAD). Increased mtFAO capacity in ob/ob liver was associated with enhanced CPT activity and/or CPT1 expression, and higher expression of other mtFAO enzymes.
Hypofunction of anti-oxidative stress is a subtype of hypofunctioning: A process that performs a decreased or insufficient anti-oxidative stress function. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
hypofunction of anti-oxidative stress[mitochondrial disorder]
Reduced ROS detoxification could also favor oxidative stress. Indeed, several studies showed lower GSH levels in NAFLD, including within the mitochondria. Decreased expression and/or activity of antioxidant enzymes such as GPx and SODs could also occur, in particular at the mitochondrial level.
The formation of glucose from noncarbohydrate precursors, such as pyruvate, amino acids and glycerol. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
gluconeogenesis [mitochondrial disorder]
Though all tissues support minor activities of anaplerosis and cataplerosis, these pathways are a major function of liver TCA cycle, where anaplerosis and cataplerosis are required for shuttling reducing equivalents (RE) and biosynthetic substrates related to ureagenesis, amino acid synthesis, lipogenesis, and most prominently, gluconeogenesis (GNG) (1) On the whole, the data indicate that increased flux through anaplerotic/cataplerotic pathways not only contributes to dysregulation of downstream nutrients (e.g., glycemia and lipidemia), but also triggers oxidative metabolism and altered antioxidant capacity that contribute to the development of oxidative stress, inflammation, and insulin resistance (Figure 8B and Supplemental Table 2).
The chemical reactions and pathways resulting in the formation of lipids, compounds soluble in an organic solvent but not, or sparingly, in an aqueous solvent. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
lipid biosynthetic process [mitochondrial disorder]
In addition to its ability to promote de novo lipogenesis and block β-oxidation of fatty acids, fructose consumption seems to cause a drop in ATP and an elevation of uric acid, which can further induce mitochondrial oxidative stress.
Increasing demand for response to oxidative stress is a subtype of increasing the demand for response to stress: A process that changes the functional demand for the response to the oxidative stress to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
increasing demand for response to oxidative stress [mitochondrial disorder]
Furthermore, high glucose levels promote ROS overproduction within hepatocytes, thus favoring oxidative stress and mitochondrial dysfunction. Reduced ROS detoxification could also favor oxidative stress. Indeed, several studies showed lower GSH levels in NAFLD, including within the mitochondria. Decreased expression and/or activity of antioxidant enzymes such as GPx and SODs could also occur, in particular at the mitochondrial level.
MPTP is defined as the sudden increase of mitochondrial inner membrane permeability to low molecular weight solutes (1.5 kDa) in response to many stimuli, including high levels of Ca2+ and oxidant stress.
Just like in NASH, oxidative stress, mitochondrial dysfunction, and oxidized mtDNA also contribute to the progression of HCC through influences on inflammation, cell death, and ER stress. Mitochondrial ROS and oxidative stress can disrupt ER function leading to inappropriate release of calcium in liver parenchymal cells. Moreover, in vitro treatment of liver cells with saturated fatty acids (palmitic and stearic acids) reproduces mitochondrial dysfunction found in NASH, including decreasing cellular ATP content and mtDNA-encoded oxidative phosphorylation (OXPHOS) subunit expression, coupled with increased oxidative stress. In addition to its ability to promote de novo lipogenesis and block β-oxidation of fatty acids, fructose consumption seems to cause a drop in ATP and an elevation of uric acid, which can further induce mitochondrial oxidative stress. More precisely, dietary-induced hypercholesterolemia causes oxidative stress, loss of mitochondrial membrane potential, reduction in ATP content, loss of mitochondrial cristae, and hepatic steatosis in mice. Thus, accumulating evidences suggest that cholesterol overload in mitochondria induces redox imbalances leading to oxidative stress and cell death associated with steatohepatitis. Moreover, TNF-α and IL-6 promote iron accumulation, which further fuels oxidative stress-driven cell toxicity and can activate fibrogenesis and carcinogenesis in metabolic syndrome.
ketone body biosynthetic process is a subtype of generating: A process that synthesizes ketone body resulting in having output (s). This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
ketone body biosynthetic process [mitochondrial disorder]
During fasting, acetyl‐CoA moieties are mainly used to generate KB by way of ketogenesis. Hepatic ketogenesis was also augmented in mice fed a high‐fat diet (HFD),80 thus suggesting that higher acetyl‐CoA generation by way of mtFAO is followed by efficient KB production.
Negative regulation of mitochondrial respiratory chain complex I subunit phosphorylation is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of mitochondrial respiratory chain complex I subunit phosphorylation. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Negative regulation of mitochondrial respiratory chain complex I subunit phosphorylation [mitochondrial disorder]
The CyclinB1/Cdk1-mediated CI subunit phosphorylation enhances CI activity, whereas deficiency of such phosphorylation in each of the relevant CI subunits results in impairment of CI function. The mutation of Cdk1 consensus motifs severely diminished their phosphorylation. As expected, in vivo phosphorylation of each subunit at G2/M phase was inhibited in cells transfected with Cdk1 siRNA (Figure 4C, lane 3), which arrested cells at the G2/M phase (Figure S5).
A regulatory process that halts progression through the cell cycle during one of the normal phases (G1, S, G2, M). This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
cell cycle arrest [mitochondrial disorder]
As expected, in vivo phosphorylation of each subunit at G2/M phase was inhibited in cells transfected with Cdk1 siRNA (Figure 4C, lane 3), which arrested cells at the G2/M phase (Figure S5).
Increasing HMGB1 level is a subtype of increasing quantity: A process that changes the amount of HMGB1 level to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Increasing HMGB1 level [mitochondrial disorder]
Gan et al. showed that mitochondrial-free cholesterol deposition causes hepatocyte apoptosis and necrosis through c-Jun N-terminal kinase (JNK) activation, associated with increased high-mobility group box 1 (HMGB1), and cytolytic effects on neighboring hepatocytes driven by Toll-like receptor 4 (TLR4). Hepatocyte free cholesterol lipotoxicity results from JNK1-mediated mitochondrial injury and is HMGB1 and TLR4-dependent.
TLR4 signaling is a subtype of TLR signaling [biological]: Any series of molecular signals generated as a consequence of binding to toll-like receptor 4. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Malfunctioning of insulin signaling is a subtype of malfunctioning process: A process that cannot perform insulin signaling [biological] appropriately or cannot realize it at all. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Malfunctioning of insulin signaling [mitochondrial disorder]
lipotoxicity and inflammation can interfere with insulin signaling pathway to cause hepatic insulin resistance; As a result, fatty acids especially diacylglycerol and ceramide may excessively accumulate in liver tissue. Previous report has shown that diacylglycerol can activate PKC to impair insulin signal pathway. Moreover, ceramide also activates PKC to suppress protein kinase AKT and further inhibits insulin signal pathway. In conclusion, mitochondrial dysfunction gives rise to hepatic fatty acid accumulation, which ultimately impairs insulin signal pathway and causes hepatic insulin resistance.
Inflammasome activation is a subtype of activating: A process that changes the activity of the inflammasome to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
inflammasome activation [mitochondrial disorder]
TNFΑ (canonical)[mitochondrial disorder]
HIF1A activation is a subtype of molecular activation: A process that changes the activity of the HIF1A (hypoxia inducible factor 1 subunit alpha) to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
HIF1A activation [mitochondrial disorder]
TNF‐α is able to impair MRC activity, possibly by inducing hypoxia inducible factor‐1α (HIF‐1α) and mtDNA damage.
TNF-α may also alter electron transport chain (ETC) by inducing hypoxia-inducible factor -1α and mtDNA damage.
iNOS production is a subtype of protein production: A process that makes existent of iNOS ( inducible nitric oxide synthase) due to biosynthesis, secretion, or membrane trafficking, resulting in an increase in its levels. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
inducible nitric oxide synthase production [mitochondrial disorder]
NAFLD has been associated with higher hepatic expression of the inducible nitric oxide (NO) synthase (iNOS), mainly as a consequence of tumor necrosis factor‐α (TNF‐α) overproduction by the Kupffer cells. NO can readily react with the superoxide anion, thus generating the RNS peroxynitrite, which has deleterious effects on mitochondrial function and genome.
IL-6(canonical) [mitochondrial disorder]
Hypofunction of PPARGC1A gene expression is a subtype of hypofunction of transcription, DNA-templated: A process that performs a decreased or insufficient PPARGC1A gene expression. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Hypofunction of PPARGC1A gene expression [mitochondrial disorder]
Finally, higher FOXO1 activity and oxidative stress could be involved, by way of impaired mitochondrial biogenesis. Indeed, FoxO1 activation is able to reduce the content of different MRC polypeptides, possibly by decreasing heme synthesis and impairing PGC1α activity. Interestingly, oxidative stress and inflammation are able to reduce PGC1α expression.
Decreased mitochondrial biogenesis is associated with a reduction of PGC-1α, transcription factor A, mitochondrial (TFAM), or PPARs in fatty livers.
Increasing IL-6 level is a subtype of increasing quantity: A process that changes the amount of IL-6 level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing IL-6 level [hepatocarcinogenesis]
Epigenetic changes caused by UHRF1 deficiency triggered the upregulation of CXCR4, thereby activating AKT and JNK to increase the expression and secretion of IL-6. In addition, IL-6 readily activated the JAK/STAT3/Snail signaling axis, which subsequently contributed to UHRF1 deficiency-induced EMT.
A pathologic process that involves the transformation of normal cells to a neoplastic state and resulting in polyclonal or monoclonal neoplastic cell proliferation. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
There was some evidence of carcinogenicity for male and female B6C3F1 mice exposed to 1,2-dichloropropane, as indicated by increased incidences of hepatocellular neoplasms, primarily adenomas.
In mammals, the liver plays a central role in methionine metabolism, and this essential function is lost in the progression from liver cirrhosis to hepatocarcinoma.
One of the most highly characterized lesions associated with carcinogenesis is the activation of the ras genes by point mutation. This is the first demonstration of N-ras mutations in mouse liver tumors, establishing a role for the N-ras gene in mouse liver carcinogenesis.
Recent evidence has also implicated a role for cytoplasmic cyclin A accumulation in oncogenesis and cellular transformation. Consistent with this notion, it has been shown that targeting of cyclin A to the ER in normal rat fibroblasts leads to several hallmarks of cancer, including polyploidy, abnormal centrosome duplication, and genomic instability.
Enhanced hepatocarcinogenesis in Pim-3 transgenic mice
Long-term chemical carcinogenesis bioassays showed that styrene caused lung cancers in several strains of mice and mammary cancers in rats and styrene-7,8-oxide caused tumours of the forestomach in rats and mice and of the liver in mice.
Exogenous Overexpression of KIAA0101 tv1 Induced NIH3T3 Cells Transformation In Vitro and In Vivo. These results suggest that KIAA0101 tv1 has oncogenic potential.
Carcinogenicity of naturally occurring 1-hydroxyanthraquinone in rats: induction of large bowel, liver and stomach neoplasms.
Yamamoto et al. have successfully demonstrated using CAR-deficient mice that CAR is an essential factor for PB-induced liver tumor formation following the initiation with diethylnitrosamine.
In addition, Sptlc3 mRNA expression in STAM-F mice was higher than that in db/db mice that received HFD and in B6N mice fed a choline‑deficient L-amino acid (CDAA)-defined diet. Hepatic expression of the Sptlc3 subunit of serine palmitoyltransferase is associated with the development of hepatocellular carcinoma in a mouse model of nonalcoholic steatohepatitis.
Phosphorylation of β-catenin and abnormalities in function of the E-cadherin-catenin unit lead to loss of intercellular junctions, progression in liver fibrosis, and development of cirrhosis and hepatocellular carcinoma (HCC).
Since STAT3 activity also plays a role in liver disease progression and HCC development, this may contribute to the protumourigenic environment during chronic HCV infection.
Hepatocellular carcinoma is one of the most common cancers in the world, and it is influenced by agents such as DEN, 2-AAF, phenobarbital, alcohol, aflatoxin B1 metabolite or hepatitis viruses (B and C). 2-AAF exhibits its carcinogenic effect through the formation of DNA adducts, over production of reactive oxygen species (ROS) and oxidative DNA damage.
Endoplasmic reticulum (ER) stress induction by HBV infection has been implicated in liver carcinogenesis and disease progression with chronic inflammation via enhanced inflammation, oxidative stress-mediated DNA damage, and hepatocyte proliferation.
Gephyrin suppresses lung squamous cell carcinoma development by reducing mTOR pathway activation
Alcoholic cirrhosis is the second most common risk factor for HCC in the USA and Europe. The main form of aflatoxin involved in liver carcinogenesis is aflatoxin B1 (AFB1) produced by Aspergillus sp. AFB1 predominantly causes mutations at codon 249 in the TP53 tumour suppressor gene (AGG to AGT), resulting in substitution of arginine for serine (R249S), which is rarely observed in cancers other than HCC. Aristolochic acid (AA) is a highly mutagenic compound found in plants known as Aristolichia or Asarum (Chinese wild ginger) which grow worldwide. A dose-response relationship has also been shown in Taiwan between AA exposure and risk of HCC. In most instances, and particularly in high-resource countries, HCC develops as a sequel to protracted chronic hepatitis, occurring after patients develop liver cirrhosis from HBV or HCV infection.
HBV-induced immune imbalance leads to the development of HCC as described above.
In lab animals, GEM causes peroxisome proliferation, an effect that has been associated with hepatocarcinogenesis in rats. In humans, hepatobiliary disorders, but not carcinogenesis, have been associated with GEM therapy.
Increasing production amount of reactive aldehyde is a subtype of increasing quantity: A process that changes the production amount of reactive aldehyde to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
increasing production amount of reactive aldehyde [mitochondrial disorder]
Several MRC complexes including COX are sensitive to ROS and RNS. In addition, COX can be inhibited by low levels of NO and inactivated by 4‐hydroxynonenal (4‐HNE), a reactive aldehyde generated during lipid peroxidation.
These compounds may undergo fragmentation to produce several reactive intermediates, among them, malondialdehyde and the most reactive 4-hydroxy-trans-2-nonenal. These two by-products of lipid peroxidation have been shown to interact with and inactivate ETC components, including cytochrome c oxidase, by forming adducts with this enzyme[, contributing to triggering mitochondrial dysfunction in NASH.
The appearance of chemokine (C-X-C motif) ligand 8 due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
chemokine (C-X-C motif) ligand 8 production [hepatocarcinogenesis]
In summary, our findings show that reduced PHB1 expression induces IL-8 transcription by activating NF-κB and AP-1, resulting in enhanced IL-8 expression and release to promote tumorigenesis. Conditioned medium from PHB1-silenced HepG2 cells increased migration and invasion of parental HepG2 and SK-hep-1 cells, and this was blocked by co-treatment with neutralizing IL-8 antibody.
Snail1 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the Snail1 (snail family transcriptional repressor 1) . This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Downregulation of UHRF1 increases tumor malignancy by activating the CXCR4/AKT-JNK/IL-6/Snail signaling axis in hepatocellular carcinoma cells. In addition, IL-6 readily activated the JAK/STAT3/Snail signaling axis, which subsequently contributed to UHRF1 deficiency-induced EMT. Snail siRNA markedly attenuated the upregulation of CD133 at both the mRNA and protein levels. Moreover, Snail siRNA significantly suppressed an increase in both SP fraction and the size of spheres formed. Consistent with these reports, the transient knockdown of Snail efficiently modulated not only the expression of CD133 but also the expansion of the population of cancer stem-like cells caused by UHRF1 deficiency.
Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
negative regulation of apoptotic process [hepatocarcinogenesis]
Variant 1 of KIAA0101, overexpressed in hepatocellular carcinoma, prevents doxorubicin-induced apoptosis by inhibiting p53 activation. KIAA0101 tv1 may function as a regulator, promoting cell survival in HCC through regulating the function of p53.
Further study revealed that the enhanced Noxa caused by Celastrol was the key factor for the synergy, since small interfering RNA-mediated knockdown of Noxa expression in HCC cells resulted in decreased apoptosis and attenuated anti-proliferative effects of the combination.
Importantly, the down-regulation of NOXA expression via siRNA silencing substantially attenuated apoptosis of liver cancer cells. In this study, we found that the combination of CQ with MLN4924 provoked enhanced DNA damage when compared to MLN4924 alone whereas the attenuation of DNA damage stress via simultaneous silencing of CDT1 and ORC1 significantly reduced NOXA expression and apoptotic induction upon MLN+CQ treatment.
Hypoxia-induced up-regulation of PDGF-BB in hepatic satellite cells activated the PI3K/Akt pathway in HCC cells and enhanced cell proliferation, migration, and resistance to bile acid-induced apoptosis.
MC from PB-treated rats produced and secreted enhanced levels of HBEGF and GDF15, factors found to suppress apoptosis and/or induce DNA synthesis in cultured HC and HCPREN.
Expression of catalytic inactive PCK1(C288S) mutant reduced, but not completely inhibited the cleavage of caspase-3. This is consistent with a partial inhibition of cell apoptosis by the PCK1(C288S) mutant when compared with the wild type PCK1 (Fig. 3b, c).
Increased cell survival mediated by repression of apoptosis is also a consequence of activated YAP/TAZ.
Cx32 exerts anti-apoptotic and pro-tumor effects via the epidermal growth factor receptor pathway in hepatocellular carcinoma. Cx32 facilitated HCC progression by blocking chemotherapy-induced apoptosis in vitro and in vivo via interacting with Src and thus promoting the phosphorylation of EGFR, subsequently activating the EGFR signaling pathway.
Iron accumulation is a subtype of accumulation of substances in a biological object: A process that keeps iron in an organism, tissue, organelle, or cell. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Iron accumulation [mitochondrial disorder]
Increasing ACSL1 level is a subtype of increasing quantity: A process that changes the amount of ACSL1 level to be higher.
Increasing ACSL1 level is a subtype of increasing quantity: A process that changes the amount of ACSL1 level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing ACSL1 level [hepatocarcinogenesis]
Among the five family isoforms, ACSL1 and ACSL4 are able to promote ungoverned cell growth, facilitate tumor invasion and evade programmed cell death, while ACSL3 may have relatively complex functions in different types of cancer. Upregulation of ACSL1 was found in multiple types of cancer, including colon, breast and liver cancer, and myeloma, while downregulation was found in lung squamous cell carcinoma. However, liver cancer overexpressed the long non-coding RNA (lncRNA) known as highly upregulated in liver cancer. This lncRNA could dampen miR-9 and relieve its suppression of PPARα expression and consequently turn on ACSL1 transcription. As HNF-4α is inversely associated with EMT and β-catenin signaling activity in liver and colon carcinogenesis, the ACSL-mediated modulation of HNF-4α activity could thus promote cell invasion and migration.
ACSL1 (canonical) [hepatocarcinogenesis]
Among the five family isoforms, ACSL1 and ACSL4 are able to promote ungoverned cell growth, facilitate tumor invasion and evade programmed cell death, while ACSL3 may have relatively complex functions in different types of cancer. Upregulation of ACSL1 was found in multiple types of cancer, including colon, breast and liver cancer, and myeloma, while downregulation was found in lung squamous cell carcinoma.
HNF4A inactivation is a subtype of molecular inactivation: A process that changes the activity of the HNF4A (hepatocyte nuclear factor 4 alpha) to be lower. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
HNF4A inactivation [hepatocarcinogenesis]
As HNF-4α is inversely associated with EMT and β-catenin signaling activity in liver and colon carcinogenesis, the ACSL-mediated modulation of HNF-4α activity could thus promote cell invasion and migration.
Any process that activates or increases the frequency, rate or extent of cell division. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
positive regulation of cell division [hepatocarcinogenesis]
Enhanced hepatocyte proliferation by Pim-3 overexpression The Pim-3 transgene can enhance the proliferation of hepatocytes through G-C-to-A-T transition mutations, thereby accelerating HCC development.
Silencing of NOXA significantly attenuates MLN4924+CQ apoptotic induction and liver-cancer-cell proliferation inhibition
In conclusion, elevated UHRF1 expression contributes to poor prognosis by promoting cell proliferation and metastasis in HCC.
Our results suggest that the high sensitivity of young rats to VC-induced hepatocarcinogenesis can reasonably be explained by enhanced DNA-alkylation and by increased cellular proliferation at an early age.
ICBP90 mediates Notch signaling to facilitate human hepatocellular carcinoma growth. DAPT caused inhibition of the activation of the Notch signaling pathway, followed by preventing the cells at the G0/G1 phases to enter S and G2/M phases.
Therefore, our results may suggest that downregulation of Proc mRNA in liver cells by 28 days of nongenotoxic hepatocarcinogen treatment occurs through epigenetic gene modification that may inhibit the APC/EPCR pathway to downregulate p21 WAF1/CIP1 and upregulate AKT-signaling molecules and activated p38 MAPK for preneoplastic liver cell proliferation.
Gephyrin overexpression suppressed LUSC cell proliferation, arrested cell cycle progression, and decreased the expression of cell-cycle related proteins such as cyclin D1, cyclin-dependent kinase-2 (CDK2), and proliferation-related protein proliferating cell nuclear antigen (PCNA).
These results establish that fumonisin B1 is mitogenic via accumulation of sphingoid bases rather than inhibition of complex sphingolipid biosynthesis per se. Because mitogens can often affect cell transformation, this provides a plausible molecular mechanism to explain the carcinogenicity of fumonisins.
A moving process of a tumor cell from the outside to the inside of other organ. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
tumor cell invasion [hepatocarcinogenesis]
TSLC1 and DAL‐1 are components of the TSLC cascade, which participates in organizing the actin cytoskeleton and constructing stable cell‐to‐cell adhesion.(16) It is thought that disturbances in the cell adhesion system are critical factors in the growth, invasion and metastasis of cancer cells. These results suggest that alterations to the TSLC cascade might have a role in hepatocarcinogenesis using DEN in rats. It has been suggested that inactivation of one of these two genes, TSLC1 and DAL‐1, might disrupt cell adhesion and links between the membrane and the cytoskeleton, resulting in gain of invasion and metastasis of cancer cells.
The Notch signaling pathway is emerging more and more as a major player in cancer biology, including in hepatocellular carcinoma, where persistent Notch activation may lead to HCC proliferation, invasion, and resistance to conventional cancer therapy.
Furthermore, both cell migration and invasion were enhanced by KIAA0101 tv1 overexpression in NIH3T3 cells.
By negatively modulating UHRF1 expression, we further showed that UHRF1 deficiency in itself is sufficient to increase the migratory and invasive properties of cells via inducing EMT, increasing the tumorigenic capacity of cells and leading to the expansion of cancer stem-like cells.
Moreover, upregulation of DPYD in HCC cells could promote in vitro migration, invasion, and in vivo lung metastasis, and inducing changes characteristic of epithelial-mesenchymal transition (EMT).
PVT1 expression was up-regulated in HCC tissues and cell lines. Function studies revealed that PVT1 knockdown significantly suppressed cell proliferation, migration and invasion, and induced cell apoptosis in vitro.
Conditioned medium from PHB1-silenced HepG2 cells increased migration and invasion of parental HepG2 and SK-hep-1 cells, and this was blocked by co-treatment with neutralizing IL-8 antibody.
Increasing ACSL4 level is a subtype of increasing quantity: A process that changes the amount of ACSL4 level to be higher.
Increasing ACSL4 level is a subtype of increasing quantity: A process that changes the amount of ACSL4 level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing ACSL4 level [hepatocarcinogenesis]
Among the five family isoforms, ACSL1 and ACSL4 are able to promote ungoverned cell growth, facilitate tumor invasion and evade programmed cell death, while ACSL3 may have relatively complex functions in different types of cancer. ACSL4 has been shown to be overexpressed in multiple cancer types, including colon, breast, liver and prostate cancer, while another study has shown its downregulation in gastric cancer. As HNF-4α is inversely associated with EMT and β-catenin signaling activity in liver and colon carcinogenesis, the ACSL-mediated modulation of HNF-4α activity could thus promote cell invasion and migration.
ACSL4 (canonical) [hepatocarcinogenesis]
Among the five family isoforms, ACSL1 and ACSL4 are able to promote ungoverned cell growth, facilitate tumor invasion and evade programmed cell death, while ACSL3 may have relatively complex functions in different types of cancer.
Increasing COX-2 level is a subtype of increasing quantity: A process that changes the amount of COX-2 level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing COX-2 level [hepatocarcinogenesis]
Furthermore, ACSL4 could also upregulate cyclooxygenase-2 (COX-2) expression and synergize with the latter to activate AA metabolism and cancer cell invasion. Inducible expression of ACSL4 or COX-2 dampened AA accumulation and consequently rescued cell death.
Any process that activates or increases the frequency, rate or extent of arachidonic acid metabolic process. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
positive regulation of arachidonic acid metabolic process [hepatocarcinogenesis]
Furthermore, ACSL4 could also upregulate cyclooxygenase-2 (COX-2) expression and synergize with the latter to activate AA metabolism and cancer cell invasion. However, in cancer cells, the pro-apoptotic activities of unesterified AA could be neutralized by ACSL4 (which activates AA for esterification into TAG) and COX-2 (which facilitates AA to convert to prostaglandin). Inducible expression of ACSL4 or COX-2 dampened AA accumulation and consequently rescued cell death.
Increasing AGGF1 level is a subtype of increasing quantity: A process that changes the amount of AGGF1 level to be higher.
Increasing AGGF1 level is a subtype of increasing quantity: A process that changes the amount of AGGF1 level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing AGGF1 level [hepatocarcinogenesis]
The high expression of AGGF1 expression in HCC tissue was well associated with the increased expression of VEGF and the high microvessel density (MVD). This phenomenon provided clues that the angiogenesis in HCC tissue was influenced by AGGF1 and it was a local process.
Western blotting and spearman's correlation curve verified the effect of OR3A4 on AGGF1 level and their positive association.
Increasing VEGF level is a subtype of increasing quantity: A process that changes the amount of VEGF level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing VEGF level [hepatocarcinogenesis]
AGGF1 expression was significantly correlated with tumoral VEGF expression and CD34-positive microvessel density.
AGGF1 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by AGGF1. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. This olfactory receptor gene is transcribed and contains an intact ORF, but it is predicted to be a pseudogene due to a poorly conserved 7-transmembrane domain structure.
LncRNA OR3A4 participates in the angiogenesis of hepatocellular carcinoma through modulating AGGF1/akt/mTOR pathway.
Any process that stops, prevents, or reduces the frequency, rate or extent of protein kinase B signaling, a series of reactions mediated by the intracellular serine/threonine kinase protein kinase B. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
negative regulation of AKT signaling [mitochondrial disorder]
Moreover, ceramide also activates PKC to suppress protein kinase AKT and further inhibits insulin signal pathway.
AKT signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal transmitted by the intracellular serine/threonine kinase protein kinase B (also called AKT). This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
AKT signaling (primitive) [hepatocarcinogenesis]
In HCC cells, epithelial mesenchymal transition (EMT) can be induced under hypoxia condition through the activation of Wnt/β-catenin pathway or PI3K/AKT pathway. Hypoxia-induced up-regulation of PDGF-BB in hepatic satellite cells activated the PI3K/Akt pathway in HCC cells and enhanced cell proliferation, migration, and resistance to bile acid-induced apoptosis.
Epigenetic changes caused by UHRF1 deficiency triggered the upregulation of CXCR4, thereby activating AKT and JNK to increase the expression and secretion of IL-6.
The activation of metalloprotease by the HH pathway through focal adhesion kinase/AKT signalling has been confirmed also by other studies on liver cancer.
In addition to the Wnt pathway, activated c-Src, STAT3, Akt, and Notch1 were also identified as mediators of EMT induced by HBV.
GSK3beta signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by GSK3beta. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
GSK3beta signal (primitive) [hepatocarcinogenesis]
TOR signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the TOR (Target of rapamycin) . This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
TOR signaling (primitive) [hepatocarcinogenesis]
Since HIF1α translation is dependent on PI3K-AKT-mTOR pathway, targeted inhibition of PI3K-AKT-mTOR activity (e.g. Bufalin) effectively suppressed HIF1α expression in HCC cells.
LncRNA OR3A4 participates in the angiogenesis of hepatocellular carcinoma through modulating AGGF1/akt/mTOR pathway. Together, present study revealed OR3A4 as a novel prognostic target for HCC, which regulated tumor progression and angiogenesis through AGGF1/akt/mTOR pathway.
p38 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the p38 (a Mitogen-Activated Protein Kinase). This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
p38 signaling (primitive) [hepatocarcinogenesis]
Metalloprotease activation is a subtype of activating: A process that changes the activity of the metalloprotease to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Metalloprotease activation [hepatocarcinogenesis]
Wang et al demonstrated that BRD4 is able to promote HCC cell migration and invasion in vitro and that BRD4 activity is mediated by HH signalling through the metalloproteases MMP - 2 and MMP - 9. The activation of metalloprotease by the HH pathway through focal adhesion kinase/AKT signalling has been confirmed also by other studies on liver cancer. Metalloprotease activation is not the only known downstream effector of HH pathway-induced progression in HCC.
A transition where an epithelial cell loses apical/basolateral polarity, severs intercellular adhesive junctions, degrades basement membrane components and becomes a migratory mesenchymal cell. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
epithelial to mesenchymal transition [hepatocarcinogenesis]
A decrease in E-cadherin level results in release of β-catenin from its associations and facilitates EMT, while the restored presence of E-cadherin re-establishes the altered cell phenotype.
In HCC cells, epithelial mesenchymal transition (EMT) can be induced under hypoxia condition through the activation of Wnt/β-catenin pathway or PI3K/AKT pathway.
By negatively modulating UHRF1 expression, we further showed that UHRF1 deficiency in itself is sufficient to increase the migratory and invasive properties of cells via inducing EMT, increasing the tumorigenic capacity of cells and leading to the expansion of cancer stem-like cells. Tumor malignancy is characterized by invasiveness and metastasis, which occur through EMT. In addition, IL-6 readily activated the JAK/STAT3/Snail signaling axis, which subsequently contributed to UHRF1 deficiency-induced EMT.
In vitro and in vivo inhibition models of the HH pathway confirm that HH is essential in maintaining tumour growth, metastasis and a mesenchymal phenotype.
Moreover, upregulation of DPYD in HCC cells could promote in vitro migration, invasion, and in vivo lung metastasis, and inducing changes characteristic of epithelial-mesenchymal transition (EMT). Mechanistically, DPYD functioned as a positive regulator of EMT in HCC by targeting the p38/NF-κB/Snail1 pathway. Our data evidenced that DPYD activity is highly elevated in human HCCs, where it promotes metastasis through a mechanism that involves EMT. Moreover, we also confirmed that the p38/NF-κB/Snail1 signaling by which DPYD regulates EMT and facilitates HCC progression.
In summary, loss of E-cadherin in the liver leads to sclerosing cholangitis and promotes tumorigenesis. Its tumor-promoting function seemed to be caused by gain of stem cell properties as well as induction of EMT. In addition, invasion capacity was significantly increased by E-cadherin knockdown, suggesting that loss of E-cadherin can be a causal factor of EMT and invasive phenotype of HCC.
In HBx-infected hepatoma cells, TGF-β proved to upregulate CD133 expression and induce cancer stemness and EMT. On the other hand, hypoxia-inducing factor 1α (HIF-1α) proved to enhance the EMT of HCC cells; its expression correlates with IL-1β-related inflammation intensity. Although the hypoxia microenvironment may induce EMT, the hypoxia-related EMT cascade cannot be activated without the simultaneous activation of actin cytoskeleton remodeling via the Wnt/β-catenin pathway. Hypoxia-related EMT is also linked with the aberrant hedgehog pathway which plays an important role in maintaining the stem cell capacity of tumor cells. Hypoxia could also promote the EMT of HCC cells via Twist1 upregulation.
A series of molecular signals mediated by APC (Activated protein C).
APC signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by APC.
Any process that stops, prevents, or reduces the frequency, rate or extent of APC signaling, a series of reactions mediated by APC.
Any process that stops, prevents, or reduces the frequency, rate or extent of APC signaling, a series of reactions mediated by APC. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
negative regulation of APC signaling [hepatocarcinogenesis]
Any process that stops, prevents, or reduces the frequency, rate or extent of EPCR signaling, a series of reactions mediated by EPCR. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
negative regulation of EPCR signaling [hepatocarcinogenesis]
ATF4 inactivation is a subtype of molecular inactivation: A process that changes the activity of the ATF4 (activating transcription factor 4) to be lower.
ATF4 inactivation is a subtype of molecular inactivation: A process that changes the activity of the ATF4 (activating transcription factor 4) to be lower. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
ATF4 inactivation [hepatocarcinogenesis]
As shown in Fig. 6F, while Celastrol increased Noxa mRNA level to 2.76-fold of control group, knockdown of ATF4 resulted in significant inhibition of Noxa mRNA with 1.22-fold of control group (ATF4 siRNA+Celastrol vs. control siRNA+Celastrol: p<0.05), suggesting that Celastrol-increased Noxa mRNA was ATF4-dependent.
ATF4 - inactive form (human) [hepatocarcinogenesis]
PMAIP1 inactivation is a subtype of molecular inactivation: A process that changes the activity of the PMAIP1 (phorbol-12-myristate-13-acetate-induced protein 1) to be lower. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
PMAIP1 inactivation [hepatocarcinogenesis]
Further study revealed that the enhanced Noxa caused by Celastrol was the key factor for the synergy, since small interfering RNA-mediated knockdown of Noxa expression in HCC cells resulted in decreased apoptosis and attenuated anti-proliferative effects of the combination. Then HepG2 cells transfecting Noxa siRNA were treated with 10 µM ABT-737, 1.25 µM Celastrol or the combination for another 48 h. Fig. 4B showed that Noxa-specific siRNA significantly reduced the cleavage of caspase-3 and PARP by ABT-737 in combination with Celastrol.
Importantly, the down-regulation of NOXA expression via siRNA silencing substantially attenuated apoptosis of liver cancer cells. Silencing of NOXA significantly attenuates MLN4924+CQ apoptotic induction and liver-cancer-cell proliferation inhibition. The elimination of DNA damage or blockage of ROS production significantly reduced the expression of NOXA, and thereby attenuated apoptosis and reduced growth inhibition of liver cancer cells.
ATF6 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the ATF6 (activating transcription factor 6). ATF6 generally plays a endoplasmic reticulum membrane stress sensor role. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
ATF6 signaling (primitive) [hepatocarcinogenesis]
It has been also shown that the overexpression of IP-10, which induced by liver graft injury, may lead to cisplatin resistance via ATF6/Grp78 ER stress signaling pathway in HCC; IP-10 neutralizing antibody could be a potential adjuvant therapy to sensitize HCC-cisplatin treatment.
Grp78 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by Grp78. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Grp78 signaling (primitive) [hepatocarcinogenesis]
Negative regulation of ATP transport is a subtype of negative regulation of transport: Any process that stops, prevents, or reduces the frequency, rate or extent of the directed movement of ATP into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
Negative regulation of ATP transport is a subtype of negative regulation of transport: Any process that stops, prevents, or reduces the frequency, rate or extent of the directed movement of ATP into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Negative regulation of ATP transport [mitochondrial disorder]
Similarly, dimeric organization of ADP/ATP carrier and other ADP/ATP carrier-containing supercomplexes are destabilized in CL-deficient mitochondria.
Increasing BCL-2 level is a subtype of increasing quantity: A process that changes the amount of BCL-2 level to be higher.
Increasing BCL-2 level is a subtype of increasing quantity: A process that changes the amount of BCL-2 level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing BCL-2 level [hepatocarcinogenesis]
C9ORF72 inactivation is a subtype of molecular inactivation: A process that changes the activity of the C9ORF72 (C9orf72-SMCR8 complex subunit) to be lower.
C9ORF72 inactivation is a subtype of molecular inactivation: A process that changes the activity of the C9ORF72 (C9orf72-SMCR8 complex subunit) to be lower. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
C9ORF72 inactivation [mitochondrial disorder]
We found evidence of autophagy/mitophagy in dynamic equilibrium with the biogenesis of novel mitochondria, particularly in mutant C9ORF72 fibroblasts where an increase of mitochondrial DNA content and mass, and of PGC1-α protein was observed. The autophagic process is also partially activated in mC9ORF72 as evidenced by electron microscopy data and p62 protein down-regulation. We observed a significant depolarization of mitochondria in mTDP-43 fibroblasts, where the median MMP value was approximately 80 % compared to control group, whereas in mC9ORF72 fibroblasts the median MMP value significantly increased to 129 %, indicating hyperpolarized mitochondria (Fig. 2a). We found a consistent and significant increase of mitochondrial ROS along with a parallel increase of total cellular ROS levels specifically in mC9ORF72 cells compared to both healthy control and mTDP-43 fibroblasts (Fig. 2e-​-ff).
C9orf72_inactivated (predicted)(human) [mitochondrial damage]
In the present study we showed that mutations in TARDBP and C9ORF72 genes, associated to defects in RNA metabolism in ALS and FTD neurodegenerative diseases, affect mitochondria functionality by altering several morphological and bioenergetics parameters in a gene-specific manner.
Any process that activates, maintains or increases the rate of autophagy. Autophagy is the process in which cells digest parts of their own cytoplasm. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
positive regulation of autophagy [mitochondrial disorder]
We found evidence of autophagy/mitophagy in dynamic equilibrium with the biogenesis of novel mitochondria, particularly in mutant C9ORF72 fibroblasts where an increase of mitochondrial DNA content and mass, and of PGC1-α protein was observed. The autophagic process is also partially activated in mC9ORF72 as evidenced by electron microscopy data and p62 protein down-regulation.
Any process that activates or increases the frequency, rate or extent of mitophagy. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
positive regulation of mitophagy [mitochondrial disorder]
Dysregulation of mitochondrion organization is a subtype of malfunctioning of controlling: A process that cannot perform a regulation of mitochondrion organization appropriately or cannot realize it at all. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Dysregulation of mitochondrion organization
These results suggest that an altered balance of fission and fusion processes may account for the mitochondria morphology changes observed in mTDP-43 and mC9ORF72 fibroblasts.
Increasing mitochondrial membrane potential is a subtype of increasing membrane potential: A process that changes the electrical potential of a mitochondrial membrane to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Increasing mitochondrial membrane potential [mitochondrial disorder]
We observed a significant depolarization of mitochondria in mTDP-43 fibroblasts, where the median MMP value was approximately 80 % compared to control group, whereas in mC9ORF72 fibroblasts the median MMP value significantly increased to 129 %, indicating hyperpolarized mitochondria (Fig. 2a). The increased oxygen consumption rate may reflect an efficient and tightly coupled ETC activity in mC9ORF72 fibroblasts, thus accounting for the observed higher ATP content, while the increased MMP may favour electron slippage and trigger ROS production as sustained by our experimental data.
CAR activation is a subtype of molecular activation: A process that changes the activity of the CAR (constitutive active/androstane receptor) to be higher.
CAR activation is a subtype of molecular activation: A process that changes the activity of the CAR (constitutive active/androstane receptor) to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Yamamoto et al. have successfully demonstrated using CAR-deficient mice that CAR is an essential factor for PB-induced liver tumor formation following the initiation with diethylnitrosamine. While TCPOBOP directly binds and activates mouse CAR, PB indirectly activates CAR through an unidentified cellular signaling pathway.
Moreover, epidemiological studies with phenobarbital demonstrate that such compounds do not increase the risk of liver tumors in humans.
Genes encoding DNA damage-inducible 45 (GADD45) family proteins, in particular GADD45g (GADD45 gamma) were down-regulated by treatment with either PB or CF for 4 and 13 weeks.
Hepatocellular carcinoma is one of the most common cancers in the world, and it is influenced by agents such as DEN, 2-AAF, phenobarbital, alcohol, aflatoxin B1 metabolite or hepatitis viruses (B and C).
Hypomethylation of the c-myc promoter region induced by phenobarbital in rat liver. Over-expression of Dnmt1 was observed in protein extracts isolated from the livers of rats exposed to the single dose of PB.
1,4-bis[2-(3,5-dichloropyridyloxy)]benzene [hepatocarcinogenesis]
In addition, CAR has been reported to promote hepatocarcinogenesis in response to xenobiotics in mice through inducing cell proliferation and suppressing apoptosis without DNA lesions. While TCPOBOP directly binds and activates mouse CAR, PB indirectly activates CAR through an unidentified cellular signaling pathway.
For example, 1,4-Bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) activates mouse but not human CAR, and pharmacological concentrations of androstanol repress mouse but not human CAR.
CAR - activation state (mouse) [hepatocarcinogenesis]
CCL2 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by CCL2.
CCL2 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by CCL2. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
CCL2 signaling (primitive) [hepatocarcinogenesis]
Hepatic cirrhosis is a subtype of changing hardness: A process that changes the hardness of the liver to become hard due to the replacement of normal liver tissue to scar tissue. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
hepatic cirrhosis [hepatocarcinogenesis]
In mammals, the liver plays a central role in methionine metabolism, and this essential function is lost in the progression from liver cirrhosis to hepatocarcinoma. Cirrhosis was induced with CCl4 injected intraperitoneally (0.15 ml/100 g body weight) twice a week for 9 weeks.
Alcoholic cirrhosis is the second most common risk factor for HCC in the USA and Europe. In most instances, and particularly in high-resource countries, HCC develops as a sequel to protracted chronic hepatitis, occurring after patients develop liver cirrhosis from HBV or HCV infection.
Interestingly, MTAP gene expression was also impaired in the liver of CCl4-cirrhotic rats and cirrhotic patients. Cirrhosis was induced with CCl4 injected intraperitoneally (0.15 ml/100 g body weight) twice a week for 9 weeks.
Hepatocarcinogenesis dependent chemical compound is a subtype of toxic course dependent chemical entity. This entity (drug) can participate in the course of hepatocarcinogenesis.
hepatocarcinogenesis dependent chemical compound
Increasing CCND1 level is a subtype of increasing quantity: A process that changes the amount of CCND1 level to be higher.
Increasing CCND1 level is a subtype of increasing quantity: A process that changes the amount of CCND1 level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing CCND1 level [hepatocarcinogenesis]
Moreover, gephyrin reduced mTOR pathway activation to inhibit cyclin D1 and CDK2 translation.
Any process that activates or increases the rate or extent of progression through the cell cycle. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
positive regulation of cell cycle [hepatocarcinogenesis]
Pim-3-transgenic mouse-derived hepatocytes exhibited accelerated cell cycle progression.
CDK1 inactivation is a subtype of molecular inactivation: A process that changes the activity of the CDK1 (cyclin dependent kinase 1) to be lower.
CDK1 inactivation is a subtype of molecular inactivation: A process that changes the activity of the CDK1 (cyclin dependent kinase 1) to be lower. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
CDK1 inactivation [mitochondrial disorder]
CDK1 - inactive form (predicted) (human) [mitochondrial damage]
Increasing CDK2 level is a subtype of increasing quantity: A process that changes the amount of CDK2 level to be higher.
Increasing CDK2 level is a subtype of increasing quantity: A process that changes the amount of CDK2 level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing CDK2 level [hepatocarcinogenesis]
CDT1 inactivation is a subtype of molecular inactivation: A process that changes the activity of the CDT1 (chromatin licensing and DNA replication factor 1) to be lower.
CDT1 inactivation is a subtype of molecular inactivation: A process that changes the activity of the CDT1 (chromatin licensing and DNA replication factor 1) to be lower. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
CDT1 inactivation [hepatocarcinogenesis]
In this study, we found that the combination of CQ with MLN4924 provoked enhanced DNA damage when compared to MLN4924 alone whereas the attenuation of DNA damage stress via simultaneous silencing of CDT1 and ORC1 significantly reduced NOXA expression and apoptotic induction upon MLN+CQ treatment.
CDT1 - inactive form (human) [hepatocarcinogenesis]
Removing damaged DNA stress is a subtype of removing damaged object: A process that takes a damaged DNA from an organism or tissue. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Removing damaged DNA stress [hepatocarcinogenesis]
The elimination of DNA damage or blockage of ROS production significantly reduced the expression of NOXA, and thereby attenuated apoptosis and reduced growth inhibition of liver cancer cells. In this study, we found that the combination of CQ with MLN4924 provoked enhanced DNA damage when compared to MLN4924 alone whereas the attenuation of DNA damage stress via simultaneous silencing of CDT1 and ORC1 significantly reduced NOXA expression and apoptotic induction upon MLN+CQ treatment.
Increasing COX-2 level is a subtype of increasing quantity: A process that changes the amount of COX-2 level to be higher.
COX-2 (canonical) [hepatocarcinogenesis]
Increasing CPT1 level is a subtype of increasing quantity: A process that changes the amount of CPT1 level to be higher.
CPT1(canonical) [mitochondrial disorder]
Decreasing CXCL8 level is a subtype of decreasing quantity: A process that changes the amount of CXCL8 level to be lower.
Decreasing CXCL8 level is a subtype of decreasing quantity: A process that changes the amount of CXCL8 level to be lower. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Decreasing CXCL8 level [hepatocarcinogenesis]
Over Expression of Long Non-Coding RNA PANDA Promotes Hepatocellular Carcinoma by Inhibiting Senescence Associated Inflammatory Factor IL8. Importantly, this aberrant function was attributed to its inhibitory action on cell senescence by suppressing senescence associated inflammatory chemokine IL8.
Any process that stops, prevents or reduces the frequency, rate or extent of cellular senescence. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
negative regulation of cellular senescence [hepatocarcinogenesis]
The appearance of chemokine (C-X-C motif) ligand 8 due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels.
chemokine (C-X-C motif) ligand 8 production
The spread or migration of cancer cells from one part of the body (the organ in which it first appeared) to another. The secondary tumor contains cells that are like those in the original (primary) tumor. [def-source: NCI] This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Moreover, upregulation of DPYD in HCC cells could promote in vitro migration, invasion, and in vivo lung metastasis, and inducing changes characteristic of epithelial-mesenchymal transition (EMT). Our data evidenced that DPYD activity is highly elevated in human HCCs, where it promotes metastasis through a mechanism that involves EMT.
In mouse models, it was demonstrated that proinflammatory IL-1β promoted HCC metastasis and induced poor prognosis.
CXCR3 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by CXCR3. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
The results showed that post-transplant enhanced IP-10/CXCR3 signaling in small-for-size liver grafts directly induced endothelial progenitor cell (EPC) mobilization, differentiation and neovessel formation, which further promotes tumor growth.
CXCR3 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by CXCR3.
The movement of an endothelial progenitor cell (EPC) within or between different tissues and organs of the body. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
endothelial progenitor cell mobilization [hepatocarcinogenesis]
A series of molecular signals mediated by CXCR3 (CXC chemokine receptor 3).
Increasing CXCR4 level is a subtype of increasing quantity: A process that changes the amount of CXCR4 level to be higher.
Increasing CXCR4 level is a subtype of increasing quantity: A process that changes the amount of CXCR4 level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing CXCR4 level [hepatocarcinogenesis]
Downregulation of UHRF1 increases tumor malignancy by activating the CXCR4/AKT-JNK/IL-6/Snail signaling axis in hepatocellular carcinoma cells.
JNK signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the JNK (a stress-activated protein kinase (SAPK) ). This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
JNK signaling (primitive) [hepatocarcinogenesis]
Silencing PHB1 increased c-Jun N-terminal kinase (JNK) and NF-κB activity, induced nuclear accumulation of c-JUN and p65, and enhanced their binding to the IL-8 promoter containing AP-1 and NF-κB elements.
Decreasing CYP1A2 level is a subtype of decreasing quantity: A process that changes the amount of CYP1A2 level to be lower.
Decreasing CYP1A2 level is a subtype of decreasing quantity: A process that changes the amount of CYP1A2 level to be lower. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Decreasing CYP1A2 level [hepatocarcinogenesis]
Hypofunction of 17β-Estradiol metabolic process is a subtype of hypofunction of metabolism: A process that performs a decreased or insufficient 17β-Estradiol metabolic process. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Hypofunction of 17β-Estradiol metabolic process [hepatocarcinogenesis]
Hyperfunction of CYP2E1 gene expression is a subtype of hyperfunction of cytochrome 450 gene expression: A process that performs an excesssive gene expression of CYP2E1.
A series of molecular signals mediated by Cx (Connexin).
Connexin signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by connexin.
Any process that stops, prevents, or reduces the frequency, rate or extent of connexin signaling, a series of reactions mediated by connexin.
negative regulation of connexin signaling
The addition of alkyl groups to many positions on all four bases of DNA. Alkylating agents can also modify the bases of incoming nucleotides in the course of DNA synthesis. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
In HCC, the tumor suppressor gene p53 codon 249 mutation is associated with AFB(1) exposure and mutations in the K-ras oncogene are related to vinyl chloride exposure.
Removing damaged DNA stress is a subtype of removing damaged object: A process that takes a damaged DNA from an organism or tissue.
The process of a structure formation, in n which a chemical is attatched to a segement of DNA.
The process of a structure formation, in n which a chemical is attatched to a segement of DNA. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
In molecular genetics, a DNA adduct is a segment of DNA bound to a cancer-causing chemical. This process could be the start of a cancerous cell, or carcinogenesis.
formation of DNA adducts [hepatocarcinogenesis]
The results are discussed in relation to published studies on the accumulation and persistence of etheno bases in the liver during and after exposure to vinyl chloride and on mutation spectra in the ras and p53 genes in liver tumours induced by vinyl chloride.
Most important, cyproterone acetate was found to induce formation of DNA adducts in primary cultures of human hepatocytes indicating that human liver cells have the capacity to activate cyproterone acetate to genotoxic intermediates.
These results indicate that riddelliine is a genotoxic carcinogen in rat liver and that the types of mutations induced by riddelliine are consistent with riddelliine adducts involving G:C base pairs.
Overall, these results suggested that comfrey and riddelliine produced similar types of DNA adducts and mutational spectra, and that PA in comfrey are probably responsible for mutation induction and tumor initiation in rat liver.
2-AAF exhibits its carcinogenic effect through the formation of DNA adducts, over production of reactive oxygen species (ROS) and oxidative DNA damage. MDA appears to be the most mutagenic product of lipid peroxidation, but 4-HNE is most toxic.
Malondialdehyde (MDA) is a product of lipid peroxidation and prostaglandin biosynthesis. It is mutagenic and carcinogenic and the major adduct formed by reaction with DNA, a highly fluorescent pyrimidopurinone (M1-dG), has been detected in healthy human liver and leukocyte DNA.
MDA appears to be the most mutagenic product of lipid peroxidation, but 4-HNE is most toxic.
This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
cyproterone acetate [hepatocarcinogenesis]
Mesenchyme-derived factors enhance preneoplastic growth by non-genotoxic carcinogens in rat liver. MC from CPA-treated animals showed enhanced expression and secretion of HGF, which strongly raised DNA replication of HC and HCPREN.
Drug-, radiation-induced, or spontaneous injuries to DNA that introduce deviations from its normal double-helical conformation. These changes include structural distortions that interfere with replication and transcription, as well as point mutations that disrupt base pairs and exert damaging effects on future generations through changes in DNA sequence. If the damage is minor, it can often be repaired (DNA repair); extensive damage can induce apoptosis. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
2-AAF exhibits its carcinogenic effect through the formation of DNA adducts, over production of reactive oxygen species (ROS) and oxidative DNA damage.
Proto-oncogene mutation is a subtype of changing an operand: A process that changes the nucleotide sequence of Proto-oncogene randomly and permanently. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
proto-oncogene mutation [hepatocarcinogenesis]
Our results demonstrate that the predominant mutation caused by DMBA in mouse liver tumors is a G to C transversion in Ki-ras codon 13 (DMBA is also known to form guanosine adducts), illustrating the influence of both chemical- and tissue-specific factors in determining the type of ras gene mutations in a tumor. 4-Aminoazobenzene and N-hydroxy-2-acetylaminofluorene also caused the Ki-ras codon 13 mutation. In addition, we found that N-nitrosodiethylamine, 4-aminoazobenzene, and N-hydroxy-2-acetylaminofluorene all caused G to T transversions in the N-ras gene (codons 12 or 13). This is the first demonstration of N-ras mutations in mouse liver tumors, establishing a role for the N-ras gene in mouse liver carcinogenesis. In addition, four DMBA-induced tumors had an A to T transversion in Ha-ras codon 61. One of the most highly characterized lesions associated with carcinogenesis is the activation of the ras genes by point mutation.
Mutations in the TERT promoter (occurring in 44–65% of patients with HCC and regulating transcription of the catalytic subunit of telomerase), CTNNB1 (27–40%, encoding β-catenin, a proto-oncogene in the WNT signalling pathway) and TP53 (21–31%, the master cell cycle regulator) are the most common. For example, TERT promoter and TP53 mutations are the most frequent genetic events in HBV-associated HCC, whereas CTNNB1 mutations are strongly associated with alcohol-related HCC.
Tumor suppressor gene mutation is a subtype of changing an operand: A process that changes the nucleotide sequence of Tumor suppressor gene randomly and permanently. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
tumor suppressor gene mutation [hepatocarcinogenesis]
An arginine to serine (G to T) mutation at codon 249 of the p53 tumor suppressor gene (R249S; 249ser mutation) is specific for exposure to aflatoxin and is detected in as many as 64% of patients with HCC.
In HCC, the tumor suppressor gene p53 codon 249 mutation is associated with AFB(1) exposure and mutations in the K-ras oncogene are related to vinyl chloride exposure. The p53 mutation pattern in HCC in workers exposed to VC includes point mutations in codons 175, 245, 248, 273 and 282 but it is still unclear whether these genetic changes are directly associated with exposure to VC. However, another study concluded that in humans, A:T base pair mutations in p53 induced by VC represent a specific mutational “signature”.
In the liver, p450 enzymes metabolize aflatoxin into an aflatoxin-8,9-exo-epoxide and, to a lesser extent, an aflatoxin- 8,9-endo-epoxide. The exo-epoxide is highly reactive and can form derivatives with DNA, RNA and proteins, and can react with the p53 tumor suppressor gene.
AFB1 predominantly causes mutations at codon 249 in the TP53 tumour suppressor gene (AGG to AGT), resulting in substitution of arginine for serine (R249S), which is rarely observed in cancers other than HCC. For example, TERT promoter and TP53 mutations are the most frequent genetic events in HBV-associated HCC, whereas CTNNB1 mutations are strongly associated with alcohol-related HCC.
Negative regulation of DNA repair is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of DNA repair. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
negative regulation of DNA repair [hepatocarcinogenesis]
In addition, nuclear excision repair, which is normally responsible for removing AFB1-DNA adducts, is inhibited by HBV oncogenic protein.
HOTAIR inhibits the mismatch repair (MMR) proteins, MSH2 and MSH6 and, as result, enhances the microsatellite instability (MSI) status of HCC cells.
HOTAIR (canonical) [hepatocarcinogenesis]
MSH2 - inactive form (canonical)[hepatocarcinogenesis]
MSH6 - inactive form (canonical) [hepatocarcinogenesis]
Any process that results in induction of genomic instability. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
induction of genomic instability [hepatocarcinogenesis]
Consistent with this notion, it has been shown that targeting of cyclin A to the ER in normal rat fibroblasts leads to several hallmarks of cancer, including polyploidy, abnormal centrosome duplication, and genomic instability.
2-acetamidofluorene [hepatocarcinogenesis]
Hyperfunction of DNA biosynthesis is a subtype of hyperfunction of biosynthesis: A process that performs an excessive DNA biosynthesis. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Hyperfunction of DNA biosynthesis [hepatocarcinogenesis]
Disruption of sphingolipid metabolism and stimulation of DNA synthesis by fumonisin B1. A molecular mechanism for carcinogenesis associated with Fusarium moniliforme.
Hyperfunction of DNA biosynthesis is a subtype of hyperfunction of biosynthesis: A process that performs an excessive DNA biosynthesis.
The toxicity induced by FB1 in the liver appears to play an important role during the cancer initiation, and the induction of oxidative damage and lipid peroxidation could be important initial events. The disruption of the phospholipid and n-6 fatty acid metabolic pathway, producing changes in the level of C20:4ω6, appears to be critical with respect to cancer promotion, especially at low dietary levels of FB1, where cancer promotion is effected in the absence of apoptosis and the disruption of the sphingolipid metabolic pathway. A recent study employing Northern blot (mRNA) analysis showed increased hepatic expression of HGF, TGF-α, and espe- cially TGF-β1 and c-myc during short-term feeding of FB1. Increased expression of c-myc oncogene and TGF-β1 may cooperate in the promotion of liver tumors during feeding FB1, possibly by providing an environment that selects for the growth of TGF-β1-resistant transformed liver cells
Disruption of sphingolipid metabolism and stimulation of DNA synthesis by fumonisin B1. A molecular mechanism for carcinogenesis associated with Fusarium moniliforme. Consumption of grains contaminated with Fusarium moniliforme (Sheldon) causes liver cancer in rats and has been correlated with esophageal cancer in humans. The causative agents are believed to be a family of compounds known as fumonisins, which bear remarkable structural resemblances to sphingosine and sphinganine, the long-chain (sphingoid) base backbones of sphingolipids.
The cellular metabolic process in which a cell duplicates one or more molecules of DNA. DNA replication begins when specific sequences, known as origins of replication, are recognized and bound by initiation proteins, and ends when the original DNA molecule has been completely duplicated and the copies topologically separated. The unit of replication usually corresponds to the genome of the cell, an organelle, or a virus. The template for replication can either be an existing DNA molecule or RNA. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
MC from CPA-treated animals showed enhanced expression and secretion of HGF, which strongly raised DNA replication of HC and HCPREN.
In addition, consistent with the results of GSEA, HMGB3 knockdown also inhibited the expression of cell cycle and DNA replication related genes Cyclin B1, proliferating cell nuclear antigen (PCNA) and flap structure-specific endonuclease 1 (FEN1), indicating that HMGB3 might promote the proliferation of HCC cells by regulating cell cycle and DNA replication pathway (Figure ​(Figure4D4D-F).
Tumor cell proliferation is a subtype of cell proliferation: A process of the multiplication or reproduction of tumor cells, resulting in the rapid expansion of a tumor cell population. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Tumor cell proliferation [Hepatocarcinogenesis]
TSLC1 and DAL‐1 are components of the TSLC cascade, which participates in organizing the actin cytoskeleton and constructing stable cell‐to‐cell adhesion.(16) It is thought that disturbances in the cell adhesion system are critical factors in the growth, invasion and metastasis of cancer cells. These results suggest that alterations to the TSLC cascade might have a role in hepatocarcinogenesis using DEN in rats.
Furthermore, NS5ATP9-mediated autophagy is required for promotion of tumour cell growth, and this effect could be inhibited with 3-methyladenine, chloroquine or by Beclin 1-silencing. Thus, the mechanism for NS5ATP9-promoted autophagy is Beclin 1-dependent in the condition of starvation, and for hepatoblastoma cell growth is also Beclin 1-dependent.
The HH pathway can induce glycolytic activity in myofibroblasts of liver stroma, the so-called “reverse Warburg” effect, and the products of glycolytic stromal cells stimulate the proliferation of malignant liver cells.
Next, we knocked down of PCK1 in HepG2 cells and found that depletion of PCK1 significantly increased cell proliferation (Supplementary Fig. S2b, c). Expression of catalytic inactive PCK1(C288S) mutant reduced, but not completely inhibited the cleavage of caspase-3.
Increasing DNMT1 level is a subtype of increasing quantity: A process that changes the amount of DNMT1 level to be higher.
Increasing DNMT1 level is a subtype of increasing quantity: A process that changes the amount of DNMT1 level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing DNMT1 level [hepatocarcinogenesis]
Over-expression of Dnmt1 was observed in protein extracts isolated from the livers of rats exposed to the single dose of PB. The oppose relationship between Dnmt1 activity and methylation status of c-myc gene was demonstrated.
Increasing DPYD level is a subtype of increasing quantity: A process that changes the amount of DPYD level to be higher.
Increasing DPYD level is a subtype of increasing quantity: A process that changes the amount of DPYD level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing DPYD level [hepatocarcinogenesis]
EGFR signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by EGFR. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
EGFR signaling (primitive) [hepatocarcinogenesis]
Hypoxia-activated YAP and TGF-α/EGFR pathways blunted the response of HCC cells to sorafenib.
Cx32 exerts anti-apoptotic and pro-tumor effects via the epidermal growth factor receptor pathway in hepatocellular carcinoma.
sorafenib resistance (process) is a subtype of decreasing sensitivity: A process that changes the sensitivity to sorafenib to be lower. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
sorafenib resistance (process) [hepatocarcinogenesis]
A series of molecular signals mediated by EPCR (Endothelial protein C receptor).
EPCR signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by EPCR.
Any process that stops, prevents, or reduces the frequency, rate or extent of EPCR signaling, a series of reactions mediated by EPCR.
A series of molecular signals mediated by ERK (extracellular receptor kinase).
ERK signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by ERK.
ERK signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by ERK. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
ERK signaling (primitive) [hepatocarcinogenesis]
The extracellular receptor kinase (ERK) pathway has been extensively characterized, is the most understood of the MAPK pathways, and is a key pathway of carcinogenesis. Perfluoroalkanoates, [e.g., perfluorooctanoate (PFOA)], are known peroxisome proliferators that induce hepatomegaly and hepatocarcinogenesis in rodents, and are classic non-genotoxic carcinogens that inhibit in vitro gap-junctional intercellular communication (GJIC). Inhibition of GJIC, in vitro, by PFOA depended on the activation of both ERK and phosphatidylcholine-specific phospholipase C (PC-PLC) in the dysregulation of GJIC in an oxidative-dependent mechanism.
Negative regulation of gap-junctional intercellular communication is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of gap-junctional intercellular communication. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
negative regulation of gap-junctional intercellular communication [hepatocarcinogenesis]
The results indicated that carcinogenesis and development of human hepatocellular carcinoma related with the abnormal expression of cx genes and disorder of its signal transduction pathway, such as decrease of (Ca(2+))i, post-translation phosphorylation on tyrosine of Cx proteins which led to a dramatic disruption of GJIC.
Perfluoroalkanoates, [e.g., perfluorooctanoate (PFOA)], are known peroxisome proliferators that induce hepatomegaly and hepatocarcinogenesis in rodents, and are classic non-genotoxic carcinogens that inhibit in vitro gap-junctional intercellular communication (GJIC). Inhibition of GJIC, in vitro, by PFOA depended on the activation of both ERK and phosphatidylcholine-specific phospholipase C (PC-PLC) in the dysregulation of GJIC in an oxidative-dependent mechanism.
Grp78 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by Grp78.
A series of molecular signals mediated by Grp78 (Glucose-regulated protein 78).
Increasing demand for response to ER stress is a subtype of increasing the demand for response to stress: A process that changes the functional demand for the response to the endoplasmic reticulum (ER) stress to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
increasing demand for response to ER stress [hepatocarcinogenesis]
Among these, mitochondrial dysfunction is linked to cancer progression through increased ROS production, impaired mitochondrial respiration, ER stress, and alteration of nutrient metabolism.
Inflammatory response is a subtype of changing material: The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
inflammatory response [hepatocarcinogenesis]
In most instances, and particularly in high-resource countries, HCC develops as a sequel to protracted chronic hepatitis, occurring after patients develop liver cirrhosis from HBV or HCV infection.
Increasing demand for response to oxidative stress is a subtype of increasing the demand for response to stress: A process that changes the functional demand for the response to the oxidative stress to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
increasing demand for response to oxidative stress [hepatocarcinogenesis]
The toxicity induced by FB1 in the liver appears to play an important role during the cancer initiation, and the induction of oxidative damage and lipid peroxidation could be important initial events.
A series of molecular signals mediated by FAK (focal adhesion kinase).
FAK signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by FAK.
FAK signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by FAK. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
FAK signaling (primitive) [hepatocarcinogenesis]
FAS signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by FAS.
FAS signaling is a subtype of signaling [biological]: A process that in which a signal is transmitted by FAS. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Increasing FGF21 level is a subtype of increasing quantity: A process that changes the amount of FGF21 level to be higher.
Increasing FGF21 level is a subtype of increasing quantity: A process that changes the amount of FGF21 level to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
increasing FGF21 level [mitochondrial disorder]
FGF21(canonical) [mitochondrial disorder]
A series of molecular signals mediated by FGF2.
FGF2 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by FGF2.
FGF2 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by FGF2. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
FGF2 signaling (primitive) [hepatocarcinogenesis]
In human samples with HCV-related HCC, EMT was found to be driven by the Wnt-β catenin pathway, which is probably modulated by some viral proteins, such as NS5A, or occurs as a result of bFGF activation.
WNT signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by WNT. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
WNT signaling (primitive) [hepatocarcinogenesis]
HCV also affects in a twofold way expression of E-cadherin, indirectly by modulation of the Wnt/β-catenin pathway and directly with mediation of HCV core protein. C protein diminishes expression of E-cadherin at the transcriptional level, through methylation of CpG islands in the promoter of the CDH1 gene.
In hepatocellular carcinoma (HCC), the Wnt signaling pathway is frequently activated and it is associated with an aggressive HCC phenotype. Frizzled (FZD) receptors, a family member of GPCRs, are known to mediate Wnt signaling. For HCV-related HCC, the HCV core protein induced Wnt pathway components, including the expression of FZD1/2/5/6/7/9, and further activated β-catenin/TCF transcription activity in an HCC cell line.
By contrast, the WNT/β-catenin signaling cascade is aberrantly activated in human HCC due to gain-of-function mutations in the CTNNB1 gene and loss-of-function mutations in the APC and AXIN1 genes.
The CSCs may activate the Wnt/β-catenin pathway and induce chemo/radiotherapy resistance, disease relapse, and metastasis and are also responsible for tumor heterogeneity. Although the hypoxia microenvironment may induce EMT, the hypoxia-related EMT cascade cannot be activated without the simultaneous activation of actin cytoskeleton remodeling via the Wnt/β-catenin pathway.
FOXO1 activation is a subtype of molecular activation: A process that changes the activity of the FOXO1 (forkhead box O1) to be higher.
FOXO1 activation is a subtype of molecular activation: A process that changes the activity of the FOXO1 (forkhead box O1) to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
FOXO1 activation [mitochondrial disorder]
Finally, higher FOXO1 activity and oxidative stress could be involved, by way of impaired mitochondrial biogenesis. Indeed, FoxO1 activation is able to reduce the content of different MRC polypeptides, possibly by decreasing heme synthesis and impairing PGC1α activity. Reduced PGC1α activity could also be secondary to oxidative stress and inflammation, as previously mentioned (Fig. 4). Interestingly, oxidative stress and inflammation are able to reduce PGC1α expression.
FOXO1 - activation state (canonical)[mitochondrial disorder]
Hypofunction of heme biosynthesis is a subtype of hypofunction of biosynthesis: A process that performs a decreased or insufficient heme biosynthesis. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Hypofunction of heme biosynthesis [mitochondrial disorder]
Decreasing GADD45G level is a subtype of decreasing quantity: A process that changes the amount of GADD45G level to be lower.
Decreasing GADD45G level is a subtype of decreasing quantity: A process that changes the amount of GADD45G level to be lower. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Decreasing GADD45G level [hepatocarcinogenesis]
Genes encoding DNA damage-inducible 45 (GADD45) family proteins, in particular GADD45g (GADD45 gamma) were down-regulated by treatment with either PB or CF for 4 and 13 weeks. Since GADD45 functions as a chemical and radiation stress sensor by interacting with cyclins and cyclin-dependent kinase inhibitors, the decrease in the gene expression of GADD45g mRNA observed in this study, may be associated with nongenotoxic chemical-induced tumor promotion of hepatocarcinogenesis rather than liver hypertrophy.
For example, PP such as clofibrate and gemfibrozil, are highly effective lipid and cholesterol lowering drugs in humans but do not cause peroxisome proliferation and there is no evidence for increased liver cancers in patients receiving these drugs.
Increasing GDF15 level is a subtype of increasing quantity: A process that changes the amount of GDF15 level to be higher.
Increasing GDF15 level is a subtype of increasing quantity: A process that changes the amount of GDF15 level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing GDF15 level [hepatocarcinogenesis]
MC from PB-treated rats produced and secreted enhanced levels of HBEGF and GDF15, factors found to suppress apoptosis and/or induce DNA synthesis in cultured HC and HCPREN. These observations provide indirect but compelling evidence that the elevated HBEGF levels in SN/MC-PB may mediate the pro-survival effects of PB in HC (Fig. 8).
Negative regulation of gap-junctional intercellular communication is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of gap-junctional intercellular communication.
negative regulation of gap-junctional intercellular communication
Decreasing GPHN level is a subtype of decreasing quantity: A process that changes the amount of GPHN level to be lower.
Decreasing GPHN level is a subtype of decreasing quantity: A process that changes the amount of GPHN level to be lower. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Decreasing GPHN level [hepatocarcinogenesis]
Our results show that gephyrin was reduced in LUAD and LUSC, and its low expression in LUSC patients indicated poor prognosis. Conversely, knockdown of gephyrin promoted LUSC cell growth. Gephyrin suppresses lung squamous cell carcinoma development by reducing mTOR pathway activation
A series of molecular signals mediated by GSK3beta (glycogen synthase kinase 3 beta).
GSK3beta signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by GSK3beta.
beta-catenin signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by beta-catenin. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
beta-catenin signaling (primitive) [hepatocarcinogenesis]
Phosphorylation of β-catenin and abnormalities in function of the E-cadherin-catenin unit lead to loss of intercellular junctions, progression in liver fibrosis, and development of cirrhosis and hepatocellular carcinoma (HCC). A decrease in E-cadherin level results in release of β-catenin from its associations and facilitates EMT, while the restored presence of E-cadherin re-establishes the altered cell phenotype. HCV also affects in a twofold way expression of E-cadherin, indirectly by modulation of the Wnt/β-catenin pathway and directly with mediation of HCV core protein. C protein diminishes expression of E-cadherin at the transcriptional level, through methylation of CpG islands in the promoter of the CDH1 gene.
By contrast, the WNT/β-catenin signaling cascade is aberrantly activated in human HCC due to gain-of-function mutations in the CTNNB1 gene and loss-of-function mutations in the APC and AXIN1 genes. β-catenin plays key roles in multiple processes of chronic inflammation-related liver pathophysiology, including hepatocyte proliferation, stellate-cell activation, liver fibrosis and liver tumorigenesis.
Although the hypoxia microenvironment may induce EMT, the hypoxia-related EMT cascade cannot be activated without the simultaneous activation of actin cytoskeleton remodeling via the Wnt/β-catenin pathway.
cisplatin resistance (process) is a subtype of decreasing sensitivity: A process that changes the sensitivity to cisplatin to be lower. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
cisplatin resistance [hepatocarcinogenesis]
Increasing HBEGF level is a subtype of increasing quantity: A process that changes the amount of HBEGF level to be higher.
Increasing HBEGF level is a subtype of increasing quantity: A process that changes the amount of HBEGF level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing HBEGF level [hepatocarcinogenesis]
HBV infection is a subtype of pathogen colonization: A process that makes HBV present in the liver to increase the number.
HBV infection is a subtype of pathogen colonization: A process that makes HBV present in the liver to increase the number. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
For example, TERT promoter and TP53 mutations are the most frequent genetic events in HBV-associated HCC, whereas CTNNB1 mutations are strongly associated with alcohol-related HCC. Chronic HBV and HCV infection are the most important causes of HCC and account for 80% of HCC cases globally. In most instances, and particularly in high-resource countries, HCC develops as a sequel to protracted chronic hepatitis, occurring after patients develop liver cirrhosis from HBV or HCV infection. Hepatocyte necrosis and regeneration from chronic HBV infection also increase the probability of the AFB1-induced TP53 mutations. In addition, nuclear excision repair, which is normally responsible for removing AFB1-DNA adducts, is inhibited by HBV oncogenic protein.
HBV-induced immune imbalance leads to the development of HCC as described above. Persistent presence of HBV led to elevated TGF-β which suppressed miR-34a expression and enhanced CCL22 expression, thus recruiting Tregs in the liver tissue. The increased Tregs not only suppressed HBV antigen-specific immune responses, but also suppressed HCC tumor antigen-specific immune responses.
In HBx-infected hepatoma cells, TGF-β proved to upregulate CD133 expression and induce cancer stemness and EMT. In addition to the Wnt pathway, activated c-Src, STAT3, Akt, and Notch1 were also identified as mediators of EMT induced by HBV.
Notch signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by Notch. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
The Notch signaling pathway is emerging more and more as a major player in cancer biology, including in hepatocellular carcinoma, where persistent Notch activation may lead to HCC proliferation, invasion, and resistance to conventional cancer therapy. Tbale 1
ICBP90 mediates Notch signaling to facilitate human hepatocellular carcinoma growth. DAPT caused inhibition of the activation of the Notch signaling pathway, followed by preventing the cells at the G0/G1 phases to enter S and G2/M phases. On the contrary, Jagged-1, a Notch ligand, facilitated ICBP90 production. Our novel findings strongly indicate that inactivation of the Notch signaling pathway impedes hepatocellular carcinoma progress via reduction of ICBP90.
It exerts an antiapoptotic effect via the Notch-1/NF-κB pathway and interacts with the genes involved in apoptosis, such as Bcl-2, cyclin D1, survivin, and cIAPs (cellular inhibitor of apoptosis). In addition to the Wnt pathway, activated c-Src, STAT3, Akt, and Notch1 were also identified as mediators of EMT induced by HBV.
STAT3 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the STAT3 (signal transducer and activator of transcription 3) . This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
STAT3 signaling (primitive) [hepatocarcinogenesis]
In addition, IL-6 readily activated the JAK/STAT3/Snail signaling axis, which subsequently contributed to UHRF1 deficiency-induced EMT.
TGF beta receptor signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal transmitted by the TGF beta receptor (transforming growth factor beta receptor) on the surface of a cell, starting with a ligand binding to a TGFR. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
TGF beta receptor signaling (primitive) [hepatocarcinogenesis]
A recent study employing Northern blot (mRNA) analysis showed increased hepatic expression of HGF, TGF-α, and especially TGF-β1 and c-myc during short-term feeding of FB1. Increased expression of c-myc oncogene and TGF-β1 may cooperate in the promotion of liver tumors during feeding FB1, possibly by providing an environment that selects for the growth of TGF-β1-resistant transformed liver cells.
Therefore, our results may suggest that treatment with nongenotoxic hepatocarcinogens for 28 days induces epigenetic gene modification of Ldlrad4 in liver cells, which triggers the disruptive activation of TGF-β signaling for cancer development.
Persistent presence of HBV led to elevated TGF-β which suppressed miR-34a expression and enhanced CCL22 expression, thus recruiting Tregs in the liver tissue.
In HBx-infected hepatoma cells, TGF-β proved to upregulate CD133 expression and induce cancer stemness and EMT.
c-Src signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by c-Src. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
c-Src signaling (primitive) [hepatocarcinogenesis]
Telomerase reverse transcriptase gene mutation is a subtype of changing an operand: A process that changes the nucleotide sequence of Telomerase reverse transcriptase gene randomly and permanently. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
telomerase reverse transcriptase gene mutation [hepatocarcinogenesis]
A type of cell death that is morphologically characterized by an increasingly translucent cytoplasm, swelling of organelles, minor ultrastructural modifications of the nucleus (specifically, dilatation of the nuclear membrane and condensation of chromatin into small, irregular, circumscribed patches) and increased cell volume (oncosis), culminating in the disruption of the plasma membrane and subsequent loss of intracellular contents. Necrotic cells do not fragment into discrete corpses as their apoptotic counterparts do. Moreover, their nuclei remain intact and can aggregate and accumulate in necrotic tissues. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
MP HCl is an hepatotoxic hepatocarcinogen that promotes cancer by inducing necrosis/regeneration.
Hepatocyte necrosis and regeneration from chronic HBV infection also increase the probability of the AFB1-induced TP53 mutations.
Dysregulation of immune balance is a subtype of malfunctioning of controlling: A process that cannot perform a regulation of immune balance appropriately or cannot realize it at all. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
dysregulation of immune balance [hepatocarcinogenesis]
Hepatocyte regeneration is a subtype of changing material: The regrowth of lost or destroyed hepatocytes. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
hepatocyte regeneration [hepatocarcinogenesis]
HCV infection is a subtype of pathogen colonization: A process that makes HCV present in the liver to increase the number.
HCV infection is a subtype of pathogen colonization: A process that makes HCV present in the liver to increase the number. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
PPARα activation is essential for HCV core protein–induced hepatic steatosis and hepatocellular carcinoma in mice.
Our data demonstrate HCV-induced upregulation of miR-135a-5p expression is a cause of PTPRD silencing (figure 3D) and that high miR-135a-5p levels in liver tissues significantly (p=0.04, one-tailed Spearman's correlation test) correlate with low PTPRD levels and vice versa. We conclude that HCV promotes a STAT3 transcriptional programme in the liver of patients by suppressing its regulator PTPRD via upregulation of miR-135a-5p.
For HCV-related HCC, the HCV core protein induced Wnt pathway components, including the expression of FZD1/2/5/6/7/9, and further activated β-catenin/TCF transcription activity in an HCC cell line.
Chronic HBV and HCV infection are the most important causes of HCC and account for 80% of HCC cases globally. In most instances, and particularly in high-resource countries, HCC develops as a sequel to protracted chronic hepatitis, occurring after patients develop liver cirrhosis from HBV or HCV infection.
Increasing MIR135A level is a subtype of increasing quantity: A process that changes the amount of MIR135A level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing MIR135A level [hepatocarcinogenesis]
PPARalpha activation is a subtype of activating nuclear receptor: A process that changes the activity of the activating PPAR alpha ( (Peroxisome Proliferator Activated Receptor Alpha)) with a nuclear receptor role to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
PPARalpha activation [hepatocarcinogenesis]
However, long-term treatment of these mice with clofibrate, a PPARalpha activator, induced HCC with mitochondrial abnormalities and hepatic steatosis. Thus, our results indicate that persistent activation of PPARalpha is essential for the pathogenesis of hepatic steatosis and HCC induced by HCV infection.
HGFR signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by HGFR. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
HGFR signaling (primitive) [hepatocarcinogenesis]
The suppressor of cytokine signaling 1 (SOCS1) was recently shown, in HCC lines, to regulate the HGF signal; SOCS1 inhibited the HGF-induced MET-mediated cell growth/proliferation, the invasion of the extracellular matrix, and the dissemination of tumor cells. The HGF/MET axis promotes angiogenesis via interaction with proangiogenic factors such as the vascular endothelial growth factor receptor (VEGFR2) and reverse correlation with thrombospondin-1. Hypoxia stimulates c-MET overexpression in HCC cells.
HGFR signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by HGFR.
Increasing HGF level is a subtype of increasing quantity: A process that changes the amount of HGF level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing HGF level [hepatocarcinogenesis]
The HGF/MET axis promotes angiogenesis via interaction with proangiogenic factors such as the vascular endothelial growth factor receptor (VEGFR2) and reverse correlation with thrombospondin-1. Hypoxia stimulates c-MET overexpression in HCC cells.
neovascularization is a subtype of biological structure formation: A process that constructs an alternate blood vessels. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
neovascularization [hepatocarcinogenesis]
The enhanced hepatocarcinogenesis in Pim-3 transgenic mice may mirror the fact that neovascularization, an essential process for hepatocarcinogenesis, was augmented in Pim-3 transgenic mice compared with that observed for WT mice, as demonstrated by increases in CD31-positive areas in the liver (Figures 5f and g).
Taken together, increased AGGF1 expression is associated with tumor angiogenesis and serves as an independent unfavorable prognostic factor for OS and DFS in HCC.
Increasing HGF level is a subtype of increasing quantity: A process that changes the amount of HGF level to be higher.
HHIP inactivation is a subtype of molecular inactivation: A process that changes the activity of the HHIP (hedgehog interacting protein) to be lower.
HHIP inactivation is a subtype of molecular inactivation: A process that changes the activity of the HHIP (hedgehog interacting protein) to be lower. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
HHIP inactivation [hepatocarcinogenesis]
These data suggest that the trimeric UHRF1 repression complex might play a crucial role in deep silencing of the TSGs HHIP, IGFBP3, and SFRP1 in HB via combined epigenetic mechanisms, comprising repressive histone modification and DNA methylation. In particular, the silencing of the TSGs hedgehog-interacting protein (HHIP), insulin-like growth factor-binding protein 3 (IGFBP3), and secreted frizzled-related protein 1 (SFRP1) have been shown to deregulate pivotal pathways of embryonic development, thus promoting HB pathogenesis.
hedgehog interacting protein [hepatocarcinogenesis]
HHIP - inactive form (human) [hepatocarcinogenesis]
In particular, the silencing of the TSGs hedgehog-interacting protein (HHIP), insulin-like growth factor-binding protein 3 (IGFBP3), and secreted frizzled-related protein 1 (SFRP1) have been shown to deregulate pivotal pathways of embryonic development, thus promoting HB pathogenesis.
trimeric UHRF1 repression complex (human) [hepatocarcinogenesis]
The complex comprises three subunits, namely DNA methyltransferase 1 (DNMT1), ubiquitin-specific-processing protease 7 (USP7), and E3 ubiquitin-like containing PHD and RING finger domain 1 (UHRF1). We found the complex to be located on the promoter regions of the pivotal HB-associated tumor suppressor genes (TSGs) HHIP, IGFBP3, and SFRP1 in HB cells, thereby leading to strong repression through DNA methylation and histone modifications.
HIF1A activation is a subtype of molecular activation: A process that changes the activity of the HIF1A (hypoxia inducible factor 1 subunit alpha) to be higher.
HIF1A - activation state (canonical)[mitochondrial disorder]
Increasing HILPDA level is a subtype of increasing quantity: A process that changes the amount of HILPDA level to be higher.
Increasing HILPDA level is a subtype of increasing quantity: A process that changes the amount of HILPDA level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing HILPDA level [hepatocarcinogenesis]
Long Non-Coding RNA PVT1/miR-150/ HIG2 Axis Regulates the Proliferation, Invasion and the Balance of Iron Metabolism of Hepatocellular Carcinoma. PVT1 expression was up-regulated in HCC tissues and cell lines. Function studies revealed that PVT1 knockdown significantly suppressed cell proliferation, migration and invasion, and induced cell apoptosis in vitro. Furthermore, PVT1 could directly bind to microRNA (miR)-150 and down-regulate miR-150 expression. Hypoxia-inducible protein 2 (HIG2) was found to be one target gene of miR-150, and PVT1 knockdown could inhibit the expression of HIG2 through up-regulating miR-150 expression. Compare with shRNA scramble group, the iron uptake level was markedly inhibited in PVT1 shRNA group, which was elevated when miR-150 inhibitors were co-transfected with PVT1 shRNA vectors. Taken together, these results suggest that PVT1 may effect IRE/IRP regulatory system and cellular iron uptake by regulating miR-150/HIG2 axis.
Increasing iron uptake level is a subtype of increasing quantity: A process that changes the iron uptake level to be larger. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing iron uptake level [hepatocarcinogenesis]
Compare with shRNA scramble group, the iron uptake level was markedly inhibited in PVT1 shRNA group, which was elevated when miR-150 inhibitors were co-transfected with PVT1 shRNA vectors. Taken together, these results suggest that PVT1 may effect IRE/IRP regulatory system and cellular iron uptake by regulating miR-150/HIG2 axis.
Increasing HMGB1 level is a subtype of increasing quantity: A process that changes the amount of HMGB1 level to be higher.
HMGB1 (canonical) [mitochondrial disorder]
HNF4A inactivation is a subtype of molecular inactivation: A process that changes the activity of the HNF4A (hepatocyte nuclear factor 4 alpha) to be lower.
HNF4A - inactive form (canonical) [hepatocarcinogenesis]
hepatocellular carcinoma up-regulated long non-coding RNA
Increasing HULC level is a subtype of increasing quantity: A process that changes the amount of HULC level to be higher.
Increasing HULC level is a subtype of increasing quantity: A process that changes the amount of HULC level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing HULC level [hepatocarcinogenesis]
However, liver cancer overexpressed the long non-coding RNA (lncRNA) known as highly upregulated in liver cancer. This lncRNA could dampen miR-9 and relieve its suppression of PPARα expression and consequently turn on ACSL1 transcription.
Increasing PPARA level is a subtype of increasing quantity: A process that changes the amount of PPARA level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing PPARA level [hepatocarcinogenesis]
A series of molecular signals mediated by Hedgehog (HH).
Hedgehog signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by Hedgehog.
Hedgehog signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by Hedgehog. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Hedgehog signaling [hepatocarcinogenesis]
Mdr2-deficient mice were the optimal model to study the evolution of HCC in vivo in fibrotic livers. Mice showed progressively increasing levels of SHH, IHH, and Gli2, concomitant, in early phases, with an elevation of liver enzymes. Alcohol exposure induces the over-activation of HH signalling through the elevation of HH ligands and HH target genes in animal models and human tissues. The HH pathway can induce glycolytic activity in myofibroblasts of liver stroma, the so-called “reverse Warburg” effect, and the products of glycolytic stromal cells stimulate the proliferation of malignant liver cells. HH activation sustains the sub-population of immature liver epithelial cells that are involved in the pathogenesis of cirrhosis and HCC, and HH itself is a mediator of the alcohol-derived malignant transformation of liver cells. In vitro and in vivo inhibition models of the HH pathway confirm that HH is essential in maintaining tumour growth, metastasis and a mesenchymal phenotype. Metalloprotease activation is not the only known downstream effector of HH pathway-induced progression in HCC. Wang et al demonstrated that BRD4 is able to promote HCC cell migration and invasion in vitro and that BRD4 activity is mediated by HH signalling through the metalloproteases MMP - 2 and MMP - 9. The activation of metalloprotease by the HH pathway through focal adhesion kinase/AKT signalling has been confirmed also by other studies on liver cancer.
Hypoxia-related EMT is also linked with the aberrant hedgehog pathway which plays an important role in maintaining the stem cell capacity of tumor cells.
Mdr2-deficient mice were the optimal model to study the evolution of HCC in vivo in fibrotic livers. Mice showed progressively increasing levels of SHH, IHH, and Gli2, concomitant, in early phases, with an elevation of liver enzymes. The HH pathway is activated by ligands. In humans, three ligands have been identified: Sonic hedgehog (SHH), Indian hedgehog (IHH) and Desert hedgehog, of which SHH is the most studied.
A changing process in which cells become to have neoplastic quality. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
neoplastic cell transformation [hepatocarcinogenesis]
Recent evidence has also implicated a role for cytoplasmic cyclin A accumulation in oncogenesis and cellular transformation.
The chemical reactions and pathways resulting in the breakdown of a carbohydrate into pyruvate, with the concomitant production of a small amount of ATP and the reduction of NAD(P) to NAD(P)H. Glycolysis begins with the metabolism of a carbohydrate to generate products that can enter the pathway and ends with the production of pyruvate. Pyruvate may be converted to acetyl-coenzyme A, ethanol, lactate, or other small molecules. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
glycolytic process [hepatocarcinogenesis]
A series of molecular signals mediated by Hippo (Mst1 and Mst2 in mammals).
Hippo signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by Hippo. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Hippo signaling (primitive) [hepatocarcinogenesis]
The Hippo signaling pathway and its downstream effectors, YAP/TAZ have a strong correlation with hepatic fibrogenesis, and are critical regulators of hepatic tumorigenesis. Hippo-YAP/TAZ signaling pathway also exerts significant effects on tumor microenvironment by maintaining cancer-associated fibroblasts (CAFs) and promoting neo-angiogenesis.
Hippo signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by Hippo.
YAP signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by YAP. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
YAP signaling (primitive) [hepatocarcinogenesis]
YAP/TAZ signaling is involved in multiple facets of carcinogenesis, including promotion of cellular proliferation, induction of tissue invasion of tumor cells, and maintenance of cancer stem cells (CSCs). Increased cell survival mediated by repression of apoptosis is also a consequence of activated YAP/TAZ. The Hippo signaling pathway and its downstream effectors, YAP/TAZ have a strong correlation with hepatic fibrogenesis, and are critical regulators of hepatic tumorigenesis. Hippo-YAP/TAZ signaling pathway also exerts significant effects on tumor microenvironment by maintaining cancer-associated fibroblasts (CAFs) and promoting neo-angiogenesis.
UHRF1 production is a subtype of protein production: A process that makes existent of a UHRF1 protein due to biosynthesis or secretion resulting in an increase in its levels.
IFN alpha inactivation is a subtype of molecular inactivation: A process that changes the activity of the IFN alpha (interferon alpha) to be lower.
IFN alpha inactivation is a subtype of molecular inactivation: A process that changes the activity of the IFN alpha (interferon alpha) to be lower. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
IFN alpha inactivation [hepatocarcinogenesis]
In this study, we demonstrated that expression of dihydropyrimidine dehydrogenase (DPYD), a pyrimidine catabolic enzyme, was dose-dependently downregulated by IFN-α in HCC tissues from nude mice.
IGFBP3 inactivation is a subtype of molecular inactivation: A process that changes the activity of the IGFBP3 (insulin-like growth factor-binding protein 3) to be lower.
insulin like growth factor binding protein 3
IGFBP3 inactivation is a subtype of molecular inactivation: A process that changes the activity of the IGFBP3 (insulin-like growth factor binding protein 3) to be lower. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
IGFBP3 inactivation [hepatocarcinogenesis]
IGFBP3 - inactive form (human) [hepatocarcinogenesis]
IL-1B(canonical) [mitochondrial disorder]
IL-6 inactivation is a subtype of molecular inactivation: A process that changes the activity of the IL-6 (interleukin 6) to be lower.
IL-6 inactivation is a subtype of molecular inactivation: A process that changes the activity of the IL-6 (interleukin 6) to be lower. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
IL-6 inactivation [hepatocarcinogenesis]
In conclusion, IL-6 could induce autophagy by expressing NS5ATP9, while NS5ATP9 upregulated IL-6 levels in turn, which further induced autophagy. Conversely, autophagy decreased after IL-6 was silenced or neutralized with monoclonal antibody against human IL-6.
IL-6 - inactive form (human)[hepatocarcinogenesis]
KIAA0101 inactivation is a subtype of molecular inactivation: A process that changes the activity of the KIAA0101 (PCLAF, PCNA clamp associated factor) to be lower. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
KIAA0101 inactivation [hepatocarcinogenesis]
In conclusion, IL-6 could induce autophagy by expressing NS5ATP9, while NS5ATP9 upregulated IL-6 levels in turn, which further induced autophagy. Further studies indicated that the induction of autophagy by IL-6 could be attenuated by silencing NS5ATP9.
Increasing IL-6 level is a subtype of increasing quantity: A process that changes the amount of IL-6 level to be higher.
JAK signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the JAK (Janus kinase) . This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
JAK signaling (primitive) [hepatocarcinogenesis]
IL1 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the cytokine IL1. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
IL1 signaling (primitive) [hepatocarcinogenesis]
On the one hand, intratumoral interleukins, such as IL-1β and IL-6, are correlated with the number of proinflammatory tumor-associated macrophages. In mouse models, it was demonstrated that proinflammatory IL-1β promoted HCC metastasis and induced poor prognosis.
IL1 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the cytokine IL1.
IL-6 signaling is a subtype of signaling [biological]: Any series of molecular signals generated as a consequence of binding to Interleukin 6. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Iron accumulation is a subtype of accumulation of substances in a biological object: A process that keeps iron in an organism, tissue, organelle, or cell. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Iron accumulation [hepatocarcinogenesis]
A series of molecular signals mediated by IP-10 (Interferon Gamma Induced Protein 10kDa).
IP-10 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by IP-10.
IP-10 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by IP-10. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
IP-10 signaling (primitive) [hepatocarcinogenesis]
It has been also shown that the overexpression of IP-10, which induced by liver graft injury, may lead to cisplatin resistance via ATF6/Grp78 ER stress signaling pathway in HCC; IP-10 neutralizing antibody could be a potential adjuvant therapy to sensitize HCC-cisplatin treatment. The results showed that post-transplant enhanced IP-10/CXCR3 signaling in small-for-size liver grafts directly induced endothelial progenitor cell (EPC) mobilization, differentiation and neovessel formation, which further promotes tumor growth.
CXCL10 (canonical) [hepatocarcinogenesis]
A series of molecular signals mediated by JAK (Janus kinase).
JAK signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the JAK (Janus kinase) .
Increasing JUN level is a subtype of increasing quantity: A process that changes the amount of JUN level to be higher.
Increasing JUN level is a subtype of increasing quantity: A process that changes the amount of JUN level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing JUN level [hepatocarcinogenesis]
Trichloroethylene (TCE), dichloroacetic acid (DCA), and trichloroacetic acid (TCA) are environmental contaminants that are carcinogenic in mouse liver. In conclusion, DCA, TCA, and TCE decreased the methylation in the promoter regions for the c-jun and c-myc genes and increased the expression of their mRNA and proteins.
environmental contaminants that are carcinogenic in mouse liver. In conclusion, DCA, TCA, and TCE decreased the methylation in the promoter regions for the c-jun and c-myc genes and increased the expression of their mRNA and proteins.
The process of removing one or more methyl groups from JUN gene promoter.
The process of removing one or more methyl groups from proto-oncogene promoter.
The process of removing one or more methyl groups from JUN gene promoter. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
JUN gene promoter demethylation [hepatocarcinogenesis]
Trichloroethylene (TCE), dichloroacetic acid (DCA), and trichloroacetic acid (TCA) are environmental contaminants that are carcinogenic in mouse liver. We have previously reported that TCE decreased methylation of the c-jun and c-myc genes and increased the level of their mRNAs. In conclusion, DCA, TCA, and TCE decreased the methylation in the promoter regions for the c-jun and c-myc genes and increased the expression of their mRNA and proteins.
dichloroacetic acid [hepatocarcinogenesis]
trichloroethylene [hepatocarcinogenesis]
trichloroacetic acid [hepatocarcinogenesis]
KIAA0101 inactivation is a subtype of molecular inactivation: A process that changes the activity of the KIAA0101 (PCLAF, PCNA clamp associated factor) to be lower.
KIAA0101 - inactive form (predicted)(human) [hepatocarcinogenesis]
Any process that stops, prevents, or reduces the frequency, rate or extent of autophagy. Autophagy is the process in which cells digest parts of their own cytoplasm. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
negative regulation of autophagy [hepatocarcinogenesis]
Autophagy is one of the important regulators of the replication of hepatitis C virus and the survival of tumors. In conclusion, IL-6 could induce autophagy by expressing NS5ATP9, while NS5ATP9 upregulated IL-6 levels in turn, which further induced autophagy. Further studies indicated that the induction of autophagy by IL-6 could be attenuated by silencing NS5ATP9.
Increasing KIAA0101 level is a subtype of increasing quantity: A process that changes the amount of KIAA0101 level to be higher.
Increasing KIAA0101 tv1 level is a subtype of increasing quantity: A process that changes the amount of KIAA0101 tv1 level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing KIAA0101 tv1 level [hepatocarcinogenesis]
Variant 1 of KIAA0101, overexpressed in hepatocellular carcinoma, prevents doxorubicin-induced apoptosis by inhibiting p53 activation. KIAA0101 tv1 may function as a regulator, promoting cell survival in HCC through regulating the function of p53. Exogenous Overexpression of KIAA0101 tv1 Induced NIH3T3 Cells Transformation In Vitro and In Vivo. These results suggest that KIAA0101 tv1 has oncogenic potential.
Furthermore, both cell migration and invasion were enhanced by KIAA0101 tv1 overexpression in NIH3T3 cells. However, KIAA0101 tv1 overexpression dramatically increased the percentage of cells in the G2/M and S phases to 1.4-fold (P<0.001). Furthermore, KIAA0101 tv2 overexpression significantly decreased the percentage of HepG2 and HepG2.2.15 cells in G2/M and S phases (P<0.001), similar to shKIAA0101 tv1 in HepG2 and HepG2.2.15 cells.
KIAA0101 tv1 (predicted)(human) [hepatocarcinogenesis]
Any process that stops, prevents or reduces the frequency, rate or extent of signal transduction by p53 class mediator. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
negative regulation of signal transduction by p53 class mediator [hepatocarcinogenesis]
Decreasing LDLRAD4 level is a subtype of decreasing quantity: A process that changes the amount of LDLRAD4 level to be lower.
Decreasing LDLRAD4 level is a subtype of decreasing quantity: A process that changes the amount of LDLRAD4 level to be lower. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Decreasing LDLRAD4 level [hepatocarcinogenesis]
Among them, 4 genes, Ldlrad4, Proc, Cdh17, and Nfia, were confirmed to be hypermethylated specific to CCl4 by methylation-specific PCR analysis on day 28. Furthermore, transcript downregulation of all of these genes was confirmed in many nongenotoxic hepatocarcinogens by real-time RT-PCR analysis at all time points examined. Therefore, our results may suggest that treatment with nongenotoxic hepatocarcinogens for 28 days induces epigenetic gene modification of Ldlrad4 in liver cells, which triggers the disruptive activation of TGF-β signaling for cancer development.
The covalent transfer of a methyl group to LDLRAD4 gene promoter.
The covalent transfer of a methyl group to LDLRAD4 gene promoter. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
LDLRAD4 gene promoter methylation [hepatocarcinogenesis]
Among 52 genes, Ldlrad4, Proc, Cdh17, and Nfia were confirmed to show promoter-region hypermethylation by methylation-specific quantitative PCR analysis on day 28. Among them, 4 genes, Ldlrad4, Proc, Cdh17, and Nfia, were confirmed to be hypermethylated specific to CCl4 by methylation-specific PCR analysis on day 28.
Increasing MIR135A level is a subtype of increasing quantity: A process that changes the amount of MIR135A level to be higher.
PTPRD inactivation is a subtype of molecular inactivation: A process that changes the activity of the PTPRD (protein tyrosine phosphatase receptor type D) to be lower. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
PTPRD inactivation [hepatocarcinogenesis]
PTPRD (protein tyrosine phosphatase, receptor type, D) is a tumor suppressor gene, frequently inactivated through deletions or epigenetic mechanisms in several cancers with importance for global health. We found promoter hypermethylation in 22.2% of the paired HCC samples and restored PTPRD expression by 5-AzaC and/or TSA treatments.
We conclude that HCV promotes a STAT3 transcriptional programme in the liver of patients by suppressing its regulator PTPRD via upregulation of miR-135a-5p.
A series of molecular signals mediated by MMP7 (matrix metallopeptidase 7).
MMP7 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by MMP7. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
MMP7 signaling (primitive) [hepatocarcinogenesis]
MMP7 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by MMP7.
Increasing MYC level is a subtype of increasing quantity: A process that changes the amount of MYC level to be higher.
Increasing MYC level is a subtype of increasing quantity: A process that changes the amount of MYC level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing MYC level [hepatocarcinogenesis]
The study showed that phenobarbital stimulated persistent changes in DNA methylation, i.e. loss of methylation in the promoter region of the c-myc gene and up-regulated its mRNA level. Given the ability of c-myc gene to collaborate in the regulation of key cancer-related processes, i.e. cell proliferation and apoptosis, its deregulated expression (overexpression) by epigenetic events, can play crucial role for PB toxicity, including its carcinogenic activity.
Hypomethylation of the c-myc promoter region induced by phenobarbital in rat liver The study showed that phenobarbital stimulated persistent changes in DNA methylation, i.e. loss of methylation in the promoter region of the c-myc gene and up-regulated its mRNA level.
The process of removing one or more methyl groups from MYC gene promoter.
The process of removing one or more methyl groups from MYC gene promoter. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
MYC gene promoter demethylation [hepatocarcinogenesis]
Hypomethylation of the c-myc promoter region induced by phenobarbital in rat liver The study showed that phenobarbital stimulated persistent changes in DNA methylation, i.e. loss of methylation in the promoter region of the c-myc gene and up-regulated its mRNA level. Given the ability of c-myc gene to collaborate in the regulation of key cancer-related processes, i.e. cell proliferation and apoptosis, its deregulated expression (overexpression) by epigenetic events, can play crucial role for PB toxicity, including its carcinogenic activity.
N-nitrosodiethylamine [hepatocarcinogenesis]
In addition, we found that N-nitrosodiethylamine, 4-aminoazobenzene, and N-hydroxy-2-acetylaminofluorene all caused G to T transversions in the N-ras gene (codons 12 or 13).
N-hydroxy-2-acetamidofluorene [hepatocarcinogenesis]
4-Aminoazobenzene and N-hydroxy-2-acetylaminofluorene also caused the Ki-ras codon 13 mutation. In addition, we found that N-nitrosodiethylamine, 4-aminoazobenzene, and N-hydroxy-2-acetylaminofluorene all caused G to T transversions in the N-ras gene (codons 12 or 13).
NDUFA12 inactivation is a subtype of molecular inactivation: A process that changes the activity of the NDUFA12 (NADH:ubiquinone oxidoreductase subunit A12) to be lower.
NDUFB6 inactivation is a subtype of molecular inactivation: A process that changes the activity of the NDUFB6 (NADH:ubiquinone oxidoreductase subunit B6) to be lower.
NDUFS2 inactivation is a subtype of molecular inactivation: A process that changes the activity of the NDUFS2 (NADH:ubiquinone oxidoreductase core subunit S2) to be lower.
NDUFV1 inactivation is a subtype of molecular inactivation: A process that changes the activity of the NDUFV1 (NADH:ubiquinone oxidoreductase core subunit V1) to be lower.
NDUFV3 inactivation is a subtype of molecular inactivation: A process that changes the activity of the NDUFV3 (NADH:ubiquinone oxidoreductase core subunit V3) to be lower.
Increasing production quantity of NO is a subtype of increasing quantity: A process that changes the production amount of nitric oxide (NO) to be higher.
Increasing production quantity of NO is a subtype of increasing quantity: A process that changes the production amount of nitric oxide (NO) to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Increasing production quantity of NO [mitochondrial disorder]
NO may affect mitochondrial respiratory chain function by reacting with cytochrome c oxidase, thus interrupting electron transfer to oxygen.
Increasing production quantity of RNS is a subtype of increasing quantity: A process that changes the production amount of reactive nitrogen species (RNS) to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
increasing production quantity of RNS [mitochondrial disorder]
NRF2 inactivation is a subtype of molecular inactivation: A process that changes the activity of the NRF2 (nuclear factor 2) to be lower.
NRF2 inactivation is a subtype of molecular inactivation: A process that changes the activity of the NRF2 (nuclear factor 2) to be lower. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
NRF2 inactivation [mitochondrial disorder]
H2O2 produced by mitochondria induces antioxidant enzyme expression through AMPK-mediated activation of nuclear factor 2 (NRF2), and consistently, NRF2 knockout mice on a high-fat diet develop more severe NASH associated with decreased antioxidant response, reduced β-oxidation genes, and increased lipogenic genes.
NRF2 - inactive form (canonical) [mitochondrial disorder]
Negative regulation of antioxidant enzyme activation is a subtype of Negative regulation of enzyme activation: A process that stops, prevents, or reduces the frequency, rate or extent of antioxidant enzyme activation. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
negative regulation of antioxidant enzyme activation [mitochondrial disorder]
Hypofunction of lipid biosynthesis is a subtype of hypofunction of biosynthesis: A process that performs a decreased or insufficient lipid biosynthesis. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
hypofunction of lipid biosynthesis [mitochondrial disorder]
Notch signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by Notch.
Notch 1 (canonical) [hepatocarcinogenesis]
Notch 2 (canonical) [hepatocarcinogenesis]
Notch 3 (canonical) [hepatocarcinogenesis]
UHRF1 production is a subtype of protein production: A process that makes existent of a UHRF1 protein due to biosynthesis or secretion resulting in an increase in its levels. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
In conclusion, elevated UHRF1 expression contributes to poor prognosis by promoting cell proliferation and metastasis in HCC. Therefore, we consider that UHRF1 may prompt EMT process in HCC. Furthermore, inhibition of proliferation, migration, invasion, and epithelial-mesenchymal transition progression were observed in vitro and in vivo after UHRF1 knockdown, moreover, G2/M arrest was detected in HCC cells.
On the contrary, Jagged-1, a Notch ligand, facilitated ICBP90 production. Our novel findings strongly indicate that inactivation of the Notch signaling pathway impedes hepatocellular carcinoma progress via reduction of ICBP90.
ORC1 inactivation is a subtype of molecular inactivation: A process that changes the activity of the ORC1 (origin recognition complex subunit 1) to be lower.
ORC1 inactivation is a subtype of molecular inactivation: A process that changes the activity of the ORC1 (origin recognition complex subunit 1) to be lower. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
ORC1 inactivation [hepatocarcinogenesis]
ORC1 - inactive form (human) [hepatocarcinogenesis]
P21 associated ncRNA DNA damage activated
Increasing PANDA level is a subtype of increasing quantity: A process that changes the amount of PANDA level to be higher.
Increasing PANDA level is a subtype of increasing quantity: A process that changes the amount of PANDA level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing PANDA level [hepatocarcinogenesis]
PCK1 inactivation is a subtype of molecular inactivation: A process that changes the activity of the PCK1 (phosphoenolpyruvate carboxykinase 1) to be lower.
PCK1 inactivation is a subtype of molecular inactivation: A process that changes the activity of the PCK1 (phosphoenolpyruvate carboxykinase 1) to be lower. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
PCK1 inactivation [hepatocarcinogenesis]
PCK1 - inactive form (human) [Hepatocarcinogenesis]
Next, we knocked down of PCK1 in HepG2 cells and found that depletion of PCK1 significantly increased cell proliferation (Supplementary Fig. S2b, c).
PCK1 activation is a subtype of molecular activation: A process that changes the activity of the PCK1 (phosphoenolpyruvate carboxykinase 1) to be higher.
PCK1 activation is a subtype of molecular activation: A process that changes the activity of the PCK1 (phosphoenolpyruvate carboxykinase 1) to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
PCK1 activation [mitochondrial disorder]
Any process that stops, prevents, or reduces the frequency, rate or extent of gluconeogenesis. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
negative regulation of gluconeogenesis [mitochondrial disorder]
Increasing PCNA level is a subtype of increasing quantity: A process that changes the amount of PCNA level to be higher.
Increasing PCNA level is a subtype of increasing quantity: A process that changes the amount of PCNA level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing PCNA level [hepatocarcinogenesis]
PHB inactivation is a subtype of molecular inactivation: A process that changes the activity of the PHB (prohibitin) to be lower.
PHB inactivation is a subtype of molecular inactivation: A process that changes the activity of the PHB (prohibitin) to be lower. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
PHB - inactive form (human) [hepatocarcinogenesis]
A series of molecular signals mediated by PI3K (phosphatidylinositol-4,5-bisphosphate 3-kinase).
PI3K signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by PI3K.
PI3K signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by PI3K. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
PI3K signaling (primitive) [hepatocarcinogenesis]
PIM3 activation is a subtype of molecular activation: A process that changes the activity of the PIM3 (Pim-3 proto-oncogene, serine/threonine kinase) to be higher.
PIM3 activation is a subtype of molecular activation: A process that changes the activity of the PIM3 (Pim-3 proto-oncogene, serine/threonine kinase) to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
These observations indicate that the DEN challenge enhanced liver damage in Pim-3 transgenic mice, compared with that observed for WT mice, despite increased hepatocyte proliferation. Lipid droplet accumulation was more evident in Pim-3 transgenic mice than in WT mice, until 6 months after DEN treatment (Figure 4a). Dysplastic cells were observed and lobules were distorted in livers of Pim-3 transgenic mice, but not of WT mice, 6 months after DEN treatment (Figure 5a). The enhanced hepatocarcinogenesis in Pim-3 transgenic mice may mirror the fact that neovascularization, an essential process for hepatocarcinogenesis, was augmented in Pim-3 transgenic mice compared with that observed for WT mice, as demonstrated by increases in CD31-positive areas in the liver (Figures 5f and g). Pim-3-transgenic mouse-derived hepatocytes exhibited accelerated cell cycle progression.
Changing abnormal cellular structure is a subtype of changing structure: A process that changes the structure of the cell abnormally. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
changing abnormal cellular structure [hepatocarcinogenesis]
Dysplastic cells were observed and lobules were distorted in livers of Pim-3 transgenic mice, but not of WT mice, 6 months after DEN treatment (Figure 5a). At 10 months after the injection, nodules consisting of highly dysplastic malignant cells were observed in liver of Pim-3 transgenic mice and to a lesser extent in WT mice (Figure 5a).
Liver malfunction is a subtype of organ malfunction: A process that does not perform liver function correctly or not functioning at all. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
liver malfunction [hepatocarcinogenesis]
These observations indicate that the DEN challenge enhanced liver damage in Pim-3 transgenic mice, compared with that observed for WT mice, despite increased hepatocyte proliferation. Hepatocellular carcinoma usually arises in conditions that can cause liver cirrhosis, such as chronic hepatitis B and C viral infection, chronic alcohol consumption and intake of food contaminated with aflatoxin-B1 (Zheng et al., 2007). These conditions generally provoke continuous rounds of hepatocyte damage in the setting of chronic hepatitis or liver cirrhosis, and eventually activate resident or inflammatory non-parenchymal cells to produce growth factors and cytokines (Otani et al., 2005).
Lipid storage in liver is a subtype of lipid storage: The accumulation and maintenance in cells or tissues of lipids in the liver. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
lipid storage in liver [hepatocarcinogenesis]
Lipid droplet accumulation was more evident in Pim-3 transgenic mice than in WT mice, until 6 months after DEN treatment (Figure 4a). lipid droplet accumulation precedes the onset of DEN-induced HCC development (Wang et al., 2009)
PKC activation is a subtype of molecular activation: A process that changes the activity of the PKC ( protein kinase C) to be higher.
PKC activation is a subtype of molecular activation: A process that changes the activity of the PKC ( protein kinase C) to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
As a result, fatty acids especially diacylglycerol and ceramide may excessively accumulate in liver tissue. Previous report has shown that diacylglycerol can activate PKC to impair insulin signal pathway. Moreover, ceramide also activates PKC to suppress protein kinase AKT and further inhibits insulin signal pathway.
PMAIP1 inactivation is a subtype of molecular inactivation: A process that changes the activity of the PMAIP1 (phorbol-12-myristate-13-acetate-induced protein 1) to be lower.
PMAIP1 - inactive form (predicted)(human) [hepatocarcinogenesis]
Importantly, the down-regulation of NOXA expression via siRNA silencing substantially attenuated apoptosis of liver cancer cells.
Negative regulation of caspase-3 activation is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of caspase-3 activation. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
negative regulation of caspase-3 activation [hepatocarcinogenesis]
Then HepG2 cells transfecting Noxa siRNA were treated with 10 µM ABT-737, 1.25 µM Celastrol or the combination for another 48 h. Fig. 4B showed that Noxa-specific siRNA significantly reduced the cleavage of caspase-3 and PARP by ABT-737 in combination with Celastrol.
Increasing PPARA level is a subtype of increasing quantity: A process that changes the amount of PPARA level to be higher.
Hypofunction of PPARGC1A gene expression is a subtype of hypofunction of transcription, DNA-templated: A process that performs a decreased or insufficient PPARGC1A gene expression.
Hypofunction of PPARGC1A gene expression
PPARGC1A (canonical) [mitochondrial disorder]
Indeed, FoxO1 activation is able to reduce the content of different MRC polypeptides, possibly by decreasing heme synthesis and impairing PGC1α activity. Interestingly, oxidative stress and inflammation are able to reduce PGC1α expression.
PPARA - activation state (mouse) [hepatocarcinogenesis]
Decreasing PROC level is a subtype of decreasing quantity: A process that changes the amount of PROC level to be lower.
Decreasing PROC level is a subtype of decreasing quantity: A process that changes the amount of PROC level to be lower. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Decreasing PROC level [hepatocarcinogenesis]
Among them, 4 genes, Ldlrad4, Proc, Cdh17, and Nfia, were confirmed to be hypermethylated specific to CCl4 by methylation-specific PCR analysis on day 28. Furthermore, transcript downregulation of all of these genes was confirmed in many nongenotoxic hepatocarcinogens by real-time RT-PCR analysis at all time points examined. Therefore, our results may suggest that downregulation of Proc mRNA in liver cells by 28 days of nongenotoxic hepatocarcinogen treatment occurs through epigenetic gene modification that may inhibit the APC/EPCR pathway to downregulate p21 WAF1/CIP1 and upregulate AKT-signaling molecules and activated p38 MAPK for preneoplastic liver cell proliferation.
The covalent transfer of a methyl group to PROC gene promoter.
The covalent transfer of a methyl group to PROC gene promoter. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
PROC gene promoter methylation [hepatocarcinogenesis]
Increasing PROM1 level is a subtype of increasing quantity: A process that changes the amount of PROM1 level to be higher.
Increasing PROM1 level is a subtype of increasing quantity: A process that changes the amount of PROM1 level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing PROM1 level [hepatocarcinogenesis]
Snail siRNA markedly attenuated the upregulation of CD133 at both the mRNA and protein levels. Moreover, Snail siRNA significantly suppressed an increase in both SP fraction and the size of spheres formed. Consistent with these reports, the transient knockdown of Snail efficiently modulated not only the expression of CD133 but also the expansion of the population of cancer stem-like cells caused by UHRF1 deficiency.
Increasing PROX1 level is a subtype of increasing quantity: A process that changes the amount of PROX1 level to be higher.
Increasing PROX1 level is a subtype of increasing quantity: A process that changes the amount of PROX1 level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing PROX1 level [hepatocarcinogenesis]
A strong positive correlation was found between the levels of PROX1 and microvessel density in HCC tissues. Consequently, PROX1 activated nuclear factor κB signaling and selectively promoted expression of the proangiogenic interleukin‐8 (IL‐8) by epigenetically stimulating the IL‐8 promoter.
PTPRD inactivation is a subtype of molecular inactivation: A process that changes the activity of the PTPRD (protein tyrosine phosphatase receptor type D) to be lower.
PTPRD - inactive form (predicted)(human) [hepatocarcinogenesis]
STAT3 activation is a subtype of molecular activation: A process that changes the activity of the STAT3 to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
We conclude that HCV promotes a STAT3 transcriptional programme in the liver of patients by suppressing its regulator PTPRD via upregulation of miR-135a-5p. Since STAT3 activity also plays a role in liver disease progression and HCC development, this may contribute to the protumourigenic environment during chronic HCV infection. We have previously demonstrated that STAT3 is an indispensable host factor for HCV infection and that the viral infection is promoted by STAT3 activation.
The covalent transfer of a methyl group to PTPRD gene promoter.
The covalent transfer of a methyl group to PTPRD gene promoter. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
PTPRD gene promoter methylation [hepatocarcinogenesis]
Increasing PVT1 level is a subtype of increasing quantity: A process that changes the amount of PVT1 level to be higher.
Increasing PVT1 level is a subtype of increasing quantity: A process that changes the amount of PVT1 level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing PVT1 level [hepatocarcinogenesis]
Long Non-Coding RNA PVT1/miR-150/ HIG2 Axis Regulates the Proliferation, Invasion and the Balance of Iron Metabolism of Hepatocellular Carcinoma. PVT1 expression was up-regulated in HCC tissues and cell lines. Function studies revealed that PVT1 knockdown significantly suppressed cell proliferation, migration and invasion, and induced cell apoptosis in vitro. Furthermore, PVT1 could directly bind to microRNA (miR)-150 and down-regulate miR-150 expression. Hypoxia-inducible protein 2 (HIG2) was found to be one target gene of miR-150, and PVT1 knockdown could inhibit the expression of HIG2 through up-regulating miR-150 expression.
This gene represents a long non-coding RNA locus that has been identified as a candidate oncogene. Increased copy number and overexpression of this gene are associated with many types of cancers including breast and ovarian cancers, acute myeloid leukemia and Hodgkin lymphoma. Allelic variants of this gene are also associated with end-stage renal disease attributed to type 1 diabetes. Consistent with its association with various types of cancer, transcription of this gene is regulated by the tumor suppressor p53 through a canonical p53-binding site, and it has been implicated in regulating levels of the proto-oncogene MYC to promote tumorigenesis.
Decreasing MIR150 level is a subtype of decreasing quantity: A process that changes the amount of miR-150 level to be lower. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Decreasing MIR150 level [hepatocarcinogenesis]
Increaseing production quantity of ROS is a subtype of increasing quantity: A process that changes the production amount of reactive oxygen species, any molecules or ions formed by the incomplete one-electron reduction of oxygen, to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
increasing production quantity of ROS [hepatocarcinogenesis]
hypofunction of S-adenosylmethionine biosynthetic process is a subtype of hypofunction of biosynthesis: A process that performs a decreased or insufficient S-adenosylmethionine biosynthetic process.
hypofunction of S-adenosylmethionine biosynthetic process
hypofunction of S-adenosylmethionine biosynthetic process is a subtype of hypofunction of biosynthesis: A process that performs a decreased or insufficient S-adenosylmethionine biosynthetic process. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
hypofunction of S-adenosylmethionine biosynthetic process [mitochondrial disorder]
Decreasing glutathione level is a subtype of decreasing quantity: A process that changes the amount of glutathione level to be lower. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
decreasing glutathione level [mitochondrial disorder]
Reduced ROS detoxification could also favor oxidative stress. Indeed, several studies showed lower GSH levels in NAFLD, including within the mitochondria. Decreased expression and/or activity of antioxidant enzymes such as GPx and SODs could also occur, in particular at the mitochondrial level. Indeed, increased mitochondrial cholesterol during NAFLD could reduce mitochondrial transport of GSH, thus inducing lower mtGSH levels and oxidative stress (Fig. 4).18,50,261
SFRP1 inactivation is a subtype of molecular inactivation: A process that changes the activity of the SFRP1 (secreted frizzled related protein 1) to be lower.
SFRP1 inactivation is a subtype of molecular inactivation: A process that changes the activity of the SFRP1 (secreted frizzled related protein 1) to be lower. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
SFRP1 inactivation [hepatocarcinogenesis]
SFRP1 - inactive form (human) [hepatocarcinogenesis]
Increasing SPTLC3 level is a subtype of increasing quantity: A process that changes the amount of SPTLC3 level to be higher.
Increasing SPTLC3 level is a subtype of increasing quantity: A process that changes the amount of SPTLC3 level to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing SPTLC3 level [hepatocarcinogenesis]
A series of molecular signals mediated by SRC.
A series of molecular signals mediated by STAT3 (signal transducer and activator of transcription 3).
STAT3 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the STAT3 (signal transducer and activator of transcription 3) .
Any process that activates or increases the frequency, rate or extent of cancer stem cell division. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
positive regulation of cancer stem cell division [hepatocarcinogenesis]
Snail1 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the Snail1 (snail family transcriptional repressor 1) .
A series of molecular signals mediated by Snail1 (snail family transcriptional repressor 1).
A series of molecular signals mediated by TAZ (tafazzin).
TAZ signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by TAZ.
TAZ signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by TAZ. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
TAZ signaling (primitive) [hepatocarcinogenesis]
Hepatic fibrosis is a subtype of fibrosis: A process that replaces liver tissues to fibrous connective tissues, usually as a consequence of inflammation or other injury. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Hypofunction of TFAM gene expression is a subtype of hypofunction of transcription, DNA-templated: A process that performs a decreased or insufficient TFAM gene expression.
Hypofunction of TFAM gene expression is a subtype of hypofunction of transcription, DNA-templated: A process that performs a decreased or insufficient TFAM gene expression. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Hypofunction of TFAM gene expression [mitochondrial disorder]
TFAM (canonical) [mitochondrial disorder]
A series of molecular signals mediated by TGF-alpha (transforming growth factor alpha).
TGF-alpha signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by TGF-alpha.
TGF-alpha signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by TGF-alpha. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
TGF-alpha signaling (primitive) [hepatocarcinogenesis]
The orderly movement of a regulatory T cell from one site to another. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
regulatory T cell migration [hepatocarcinogenesis]
Persistent presence of HBV led to elevated TGF-β which suppressed miR-34a expression and enhanced CCL22 expression, thus recruiting Tregs in the liver tissue. The increased Tregs not only suppressed HBV antigen-specific immune responses, but also suppressed HCC tumor antigen-specific immune responses.
TLR4 signaling (primitive) is a subtype of TLR signaling [biological]: Any series of molecular signals generated as a consequence of binding to toll-like receptor 4.
The rupture of cell membranes and the loss of cytoplasm. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
TLR4 (canonical) [mitochondrial disorder]
TNF signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by TNF.
TNF signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by TNF. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Moreover, mitochondrial-free cholesterol sensitizes liver cells to TNFα- and Fas-mediated steatohepatitis and causes mitochondrial-reduced glutathione (mGSH) depletion, which is also reported in animal models and patients with NASH. Moreover, TNF-α and IL-6 promote iron accumulation, which further fuels oxidative stress-driven cell toxicity and can activate fibrogenesis and carcinogenesis in metabolic syndrome.
TNF signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by TNF. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
TNF signaling (primitive) [hepatocarcinogenesis]
Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating lowered oxygen tension. Hypoxia, defined as a decline in O2 levels below normoxic levels of 20.8 - 20.95%, results in metabolic adaptation at both the cellular and organismal level. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
response to hypoxia [hepatocarcinogenesis]
HIF system is implemented in hypoxia-responsive pathway. As summarized above, hypoxia pathway and HIFs are involved extensively in HCC development. Since HIF1α translation is dependent on PI3K-AKT-mTOR pathway, targeted inhibition of PI3K-AKT-mTOR activity (e.g. Bufalin) effectively suppressed HIF1α expression in HCC cells.
Hypoxia stimulates c-MET overexpression in HCC cells. On the other hand, hypoxia-inducing factor 1α (HIF-1α) proved to enhance the EMT of HCC cells; its expression correlates with IL-1β-related inflammation intensity. Although the hypoxia microenvironment may induce EMT, the hypoxia-related EMT cascade cannot be activated without the simultaneous activation of actin cytoskeleton remodeling via the Wnt/β-catenin pathway. Hypoxia-related EMT is also linked with the aberrant hedgehog pathway which plays an important role in maintaining the stem cell capacity of tumor cells. Hypoxia could also promote the EMT of HCC cells via Twist1 upregulation.
A series of molecular signals mediated by TSLC (Tumor suppressor in lung cancer-1) proteins.
TSLC signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the TSLC (Tumor suppressor in lung cancer-1) .
Any process that stops, prevents, or reduces the frequency, rate or extent of TSLC signaling, a series of reactions mediated by TSLC.
negative regulation of TSLC signalling cascade
Any process that stops, prevents, or reduces the frequency, rate or extent of TSLC signaling, a series of reactions mediated by TSLC. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
negative regulation of TSLC signaling [hepatocarcinogenesis]
Expression and DNA methylation patterns of Tslc1 and Dal-1 genes in hepatocellular carcinomas induced by N-nitrosodiethylamine in rats. TSLC1 and DAL‐1 are components of the TSLC cascade, which participates in organizing the actin cytoskeleton and constructing stable cell‐to‐cell adhesion. It is thought that disturbances in the cell adhesion system are critical factors in the growth, invasion and metastasis of cancer cells. These results suggest that alterations to the TSLC cascade might have a role in hepatocarcinogenesis using DEN in rats.
TSLC1 and DAL‐1 are components of the TSLC cascade, which participates in organizing the actin cytoskeleton and constructing stable cell‐to‐cell adhesion. It is thought that disturbances in the cell adhesion system are critical factors in the growth, invasion and metastasis of cancer cells. These results suggest that alterations to the TSLC cascade might have a role in hepatocarcinogenesis using DEN in rats.
differentially expressed in adenocarcinoma of the lung 1
Expression and DNA methylation patterns of Tslc1 and Dal-1 genes in hepatocellular carcinomas induced by N-nitrosodiethylamine in rats. TSLC1 and DAL‐1 are components of the TSLC cascade, which participates in organizing the actin cytoskeleton and constructing stable cell‐to‐cell adhesion.(16) It is thought that disturbances in the cell adhesion system are critical factors in the growth, invasion and metastasis of cancer cells.
Negative regulation of actin cytoskeleton organization is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of actin cytoskeleton organization. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
negative regulation of actin cytoskeleton organization [hepatocarcinogenesis]
Negative regulation of adherens junction assembly is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of adherens junction assembly. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
TSLC1 and DAL‐1 are components of the TSLC cascade, which participates in organizing the actin cytoskeleton and constructing stable cell‐to‐cell adhesion. It is thought that disturbances in the cell adhesion system are critical factors in the growth, invasion and metastasis of cancer cells.
Negative regulation of adherens junction assembly [hepatocarcinogenesis]
A series of molecular signals mediated by twist1.
Twist1 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by Twist1. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Twist1 signaling (primitive) [hepatocarcinogenesis]
Hypoxia could also promote the EMT of HCC cells via Twist1 upregulation.
Twist1 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by the cytokine Twist1.
TWIST1(canonical) [hepatocarcinogenesis]
The complex comprises three subunits, namely DNA methyltransferase 1 (DNMT1), ubiquitin-specific-processing protease 7 (USP7), and E3 ubiquitin-like containing PHD and RING finger domain 1 (UHRF1).
UHRF1 inactivation is a subtype of molecular inactivation: A process that changes the activity of the UHRF1 (ubiquitin like with PHD and ring finger domains 1) to be lower.
UHRF1 inactivation is a subtype of molecular inactivation: A process that changes the activity of the UHRF1 (ubiquitin like with PHD and ring finger domains 1) to be lower. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
UHRF1 inactivation [hepatocarcinogenesis]
Downregulation of UHRF1 increases tumor malignancy by activating the CXCR4/AKT-JNK/IL-6/Snail signaling axis in hepatocellular carcinoma cells. In this study, we observed that hypoxia-induced downregulation of UHRF1 contributes to the induction of the epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma cells. Epigenetic changes caused by UHRF1 deficiency triggered the upregulation of CXCR4, thereby activating AKT and JNK to increase the expression and secretion of IL-6.
UHRF1 - inactive form (predicted)(human) [hepatocarcinogenesis]
Increasing VEGF level is a subtype of increasing quantity: A process that changes the amount of VEGF level to be higher.
A series of molecular signals mediated by WNT (wingless/int-1).
WNT signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by WNT.
In particular, a study has revealed that upregulation of FZD7 is correlated with increased expression of β-catenin target genes in HCC with wild-type β-catenin, suggesting that activation of Wnt/β-catenin signaling can be a consequence of deregulation of the FZD receptors. For HCV-related HCC, the HCV core protein induced Wnt pathway components, including the expression of FZD1/2/5/6/7/9, and further activated β-catenin/TCF transcription activity in an HCC cell line.
A series of molecular signals mediated by YAP (Yes associated protein).
YAP signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by YAP.
A series of molecular signals mediated by beta-catenin.
beta-catenin signal transduction pathway
beta-catenin signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by beta-catenin.
CDH1 - inactive form (canonical) [hepatocarcinogenesis]
Ctnnb1 (canonical) [hepatocarcinogenesis]
A process that is carried out at the cellular level which results in dynamic structural changes to the arrangement of constituent parts of cytoskeletal structures comprising actin filaments and their associated proteins. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
actin cytoskeleton reorganization [hepatocarcinogenesis]
c-Src signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by c-Src.
Negative regulation of caspase-3 activation is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of caspase-3 activation.
negative regulation of caspase-3 activation
Negative regulation of activation is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of activation.
The selective interaction of the cyclin A with specific molecules in the cytoplasm, thereby inhibiting its translocation into the nucleus.
The selective interaction of the cyclin A with specific molecules in the cytoplasm, thereby inhibiting its translocation into the nucleus. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
cytoplasmic sequestering of cyclin A [hepatocarcinogenesis]
By sequestering cyclin A/Cdk2, SCAPER is capable of directing the activity of this kinase complex away from the nucleus and regulating cyclin A/Cdk2 equilibrium in distinct subcellular compartments. Recent evidence has also implicated a role for cytoplasmic cyclin A accumulation in oncogenesis and cellular transformation. Consistent with this notion, it has been shown that targeting of cyclin A to the ER in normal rat fibroblasts leads to several hallmarks of cancer, including polyploidy, abnormal centrosome duplication, and genomic instability.
Malfunctioning of centrosome duplication is a subtype of malfunctioning process: A process that cannot perform centrosome duplication appropriately or cannot realize it at all. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Malfunctioning of centrosome duplication [hepatocarcinogenesis]
Malfunctioning of cytokinesis is a subtype of malfunctioning process: A process that cannot perform cytokinesis appropriately or cannot realize it at all. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Malfunctioning of cytokinesis [hepatocarcinogenesis]
iNOS production is a subtype of protein production: A process that makes existent of iNOS ( inducible nitric oxide synthase) due to biosynthesis, secretion, or membrane trafficking, resulting in an increase in its levels.
inducible nitric oxide synthase production
NOS2 (canonical) [mitochondrial disorder]
Decreasing miR-150 level is a subtype of decreasing quantity: A process that changes the amount of miR-150 level to be lower.
Long Non-Coding RNA PVT1/miR-150/ HIG2 Axis Regulates the Proliferation, Invasion and the Balance of Iron Metabolism of Hepatocellular Carcinoma. Furthermore, PVT1 could directly bind to microRNA (miR)-150 and down-regulate miR-150 expression. Hypoxia-inducible protein 2 (HIG2) was found to be one target gene of miR-150, and PVT1 knockdown could inhibit the expression of HIG2 through up-regulating miR-150 expression.
mitochondria morphology changes is a subtype of changing shape: A process that changes the morphology of the mitochondria.
Proto-oncogene mutation is a subtype of changing an operand: A process that changes the nucleotide sequence of Tumor suppressor gene randomly and permanently.
7,12-dimethyltetraphene [hepatocarcinogenesis]
In addition, four DMBA-induced tumors had an A to T transversion in Ha-ras codon 61.
4-(phenylazo)aniline [hepatocarcinogenesis]
In HCC, the tumor suppressor gene p53 codon 249 mutation is associated with AFB(1) exposure and mutations in the K-ras oncogene are related to vinyl chloride exposure. AFB1-induced HCC in Fischer 344 rats showed activating mutations in codon 12 of K-ras, but in human HCC, the incidence of point mutation of K-ras and N-ras oncogenes was low. Afterwards, in HCC in workers exposed to VC, a high prevalence of K-ras-2 mutation was reported.
Our results demonstrate that the predominant mutation caused by DMBA in mouse liver tumors is a G to C transversion in Ki-ras codon 13 (DMBA is also known to form guanosine adducts), illustrating the influence of both chemical- and tissue-specific factors in determining the type of ras gene mutations in a tumor. 4-Aminoazobenzene and N-hydroxy-2-acetylaminofluorene also caused the Ki-ras codon 13 mutation.
In addition, we found that N-nitrosodiethylamine, 4-aminoazobenzene, and N-hydroxy-2-acetylaminofluorene all caused G to T transversions in the N-ras gene (codons 12 or 13). This is the first demonstration of N-ras mutations in mouse liver tumors, establishing a role for the N-ras gene in mouse liver carcinogenesis.
Any process that activates or increases the frequency, rate or extent of cancer stem cell division.
positive regulation of cancer stem cell division
Cancer-stem like cell proliferation is a subtype of cell proliferation: A process of the multiplication or reproduction of cancer-stem like cells, resulting in the rapid expansion of a cancer-stem like cell population.
Cancer-stem like cell proliferation is a subtype of cell proliferation: A process of the multiplication or reproduction of cancer-stem like cells, resulting in the rapid expansion of a cancer-stem like cell population. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Cancer-stem like cell proliferation [hepatocarcinogenesis]
The CSCs may activate the Wnt/β-catenin pathway and induce chemo/radiotherapy resistance, disease relapse, and metastasis and are also responsible for tumor heterogeneity.
Tumor suppressor inactivation is a subtype of molecular inactivation: A process that changes the activity of the tumor suppressor to be lower.
Tumor suppressor inactivation is a subtype of molecular inactivation: A process that changes the activity of the tumor suppressor to be lower. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Tumor suppressor inactivation [hepatocarcinogenesis]
Tumor suppressor gene mutation is a subtype of changing an operand: A process that changes the nucleotide sequence of Tumor suppressor gene randomly and permanently.
Negative regulation of actin cytoskeleton organization is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of actin cytoskeleton organization.
negative regulation of actin cytoskeleton organization
acetyl-CoA biosynthetic process is a subtype of generating: A process that synthesizes acetyl-CoA resulting in having output (s).
Decreasing adiponectin level is a subtype of decreasing quantity: A process that changes the amount of adiponectin level to be lower.
Decreasing adiponectin level is a subtype of decreasing quantity: A process that changes the amount of adiponectin level to be lower. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
decreasing adiponectin level [mitochondrial disorder]
Other mechanisms leading to impaired MRC activity could include higher levels of different lipid intermediates including free FAs, increased generation of lipid peroxidation products such as 4‐HNE, and reduced adiponectin action.
Aflatoxin-B1 is converted into aflatoxin B1-8,9 exo-epoxide, which is in turn converted into 8,9-dihydroxy-8-(N7) guanyl-9-hydroxy aflatoxin B1 adduct. This adduct is metabolized into aflatoxin B1 formaminopyrimidine adduct. These adducts are mutagenic and carcinogenic.
The main form of aflatoxin involved in liver carcinogenesis is aflatoxin B1 (AFB1) produced by Aspergillus sp.
The chemical reactions and pathways involving aflatoxin, a fungal metabolite found as a contaminant in moldy grains that induces liver cancer. Aflatoxin induces a G to T transversion at codon 249 of p53, leading to its inactivation. Aflatoxin is converted to a chemical carcinogen by P450. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
aflatoxin metabolic process [hepatocarcinogenesis]
The critically reactive metabolite of AFB1 is the exo 8,9-epoxide formed by a two-electron oxidation mainly catalyzed by CYP3A4, with contribution from CYP1A2 and other CYPs. An arginine to serine (G to T) mutation at codon 249 of the p53 tumor suppressor gene (R249S; 249ser mutation) is specific for exposure to aflatoxin and is detected in as many as 64% of patients with HCC.
Aflatoxin-B1 is converted into aflatoxin B1-8,9 exo-epoxide, which is in turn converted into 8,9-dihydroxy-8-(N7) guanyl-9-hydroxy aflatoxin B1 adduct. These adducts are mutagenic and carcinogenic. The predominant site of aflatoxin metabolism is the liver, and the major human cytochrome p450 enzymes involved in its metabolism are CYP 3A4, 3A5, 3A7 and 1A2. In the liver, p450 enzymes metabolize aflatoxin into an aflatoxin-8,9-exo-epoxide and, to a lesser extent, an aflatoxin- 8,9-endo-epoxide. The exo-epoxide is highly reactive and can form derivatives with DNA, RNA and proteins, and can react with the p53 tumor suppressor gene.
Curcumin inhibits cytochrome P450 isoenzymes, particularly CYP2A6 isoform; thereby reducing the formation of AFB1-8, 9-epoxide and other toxic metabolites causing aflatoxicosis. CYP2A13, a predominantly human respiratory tract enzyme, has been shown to be responsible for the bioconversion of AFB1 to its AFB1-8, 9-epoxide. According to a recent report, four major enzymes namely CYP1A1, CYP1A2, CYP2A6, and CYP3A4 are selectively upregulated, leading to AFB1 toxicity causing the liver damage.
Chronic HBV infection may induce the cytochrome P450s that metabolize inactive AFB1 to the mutagenic AFB1–8,9-epoxide.
aflatoxin B1 exo-8,9-epoxide [hepatocarcinogenesis]
Curcumin inhibits cytochrome P450 isoenzymes, particularly CYP2A6 isoform; thereby reducing the formation of AFB1-8, 9-epoxide and other toxic metabolites causing aflatoxicosis. CYP2A13, a predominantly human respiratory tract enzyme, has been shown to be responsible for the bioconversion of AFB1 to its AFB1-8, 9-epoxide.
CYP1A2(canonical) [hepatocarcinogenesis]
The predominant site of aflatoxin metabolism is the liver, and the major human cytochrome p450 enzymes involved in its metabolism are CYP 3A4, 3A5, 3A7 and 1A2.
According to a recent report, four major enzymes namely CYP1A1, CYP1A2, CYP2A6, and CYP3A4 are selectively upregulated, leading to AFB1 toxicity causing the liver damage.
CYP2A13 (canonical) [hepatocarcinogenesis]
CYP2A13, a predominantly human respiratory tract enzyme, has been shown to be responsible for the bioconversion of AFB1 to its AFB1-8, 9-epoxide.
CYP2A6 (canonical) [hepatocarcinogenesis]
Curcumin inhibits cytochrome P450 isoenzymes, particularly CYP2A6 isoform; thereby reducing the formation of AFB1-8, 9-epoxide and other toxic metabolites causing aflatoxicosis. According to a recent report, four major enzymes namely CYP1A1, CYP1A2, CYP2A6, and CYP3A4 are selectively upregulated, leading to AFB1 toxicity causing the liver damage.
CYP3A4(canonical) [hepatocarcinogenesis]
CYP3A5(canonical) [hepatocarcinogenesis]
CYP3A7 (canonical) [hepatocarcinogenesis]
Cyp1A1 (canonical) [hepatocarcinogenesis]
CCND1 (canonical) [hepatocarcinogenesis]
Tumor cell survial is a subtype of cell survival: A process that keeps the viability of a tumor cell. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
tumor cell survial [hepatocarcinogenesis]
Autophagy is one of the important regulators of the replication of hepatitis C virus and the survival of tumors.
In the late stage, a series of oncogenic signaling pathways activated by HBV result in immune escape, and promotes the finally developing HCC.
Any process that activates or increases the frequency, rate or extent of arachidonic acid metabolic process.
positive regulation of arachidonic acid metabolic process
Decreasing arachidonic acid level is a subtype of decreasing quantity: A process that changes the amount of arachidonic acid level to be lower.
aristolochic acid [hepatocarcinogenesis]
Aristolochic acid (AA) is a highly mutagenic compound found in plants known as Aristolichia or Asarum (Chinese wild ginger) which grow worldwide. A dose-response relationship has also been shown in Taiwan between AA exposure and risk of HCC.
A moving process of alcohol from the outside to the inside of a body. This entity is a specific course dependent process. This process can constitute the course of hepatocarcinogenesis.
Alcohol exposure induces the over-activation of HH signalling through the elevation of HH ligands and HH target genes in animal models and human tissues.
Alcoholic cirrhosis is the second most common risk factor for HCC in the USA and Europe. For example, TERT promoter and TP53 mutations are the most frequent genetic events in HBV-associated HCC, whereas CTNNB1 mutations are strongly associated with alcohol-related HCC.
NLRP3 (canonical)[mitochondrial disorder]]
Hypofunction of oxysterol biosynthesis is a subtype of hypofunction of lipid biosynthesis: A process that performs a decreased or insufficient oxysterol biosynthesis.
Hypofunction of oxysterol biosynthesis is a subtype of hypofunction of lipid biosynthesis: A process that performs a decreased or insufficient oxysterol biosynthesis. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
hypofunction of oxysterol biosynthesis [mitochondrial disorder]
The cellular catabolic process in which cells digest parts of their own cytoplasm; allows for both recycling of macromolecular constituents under conditions of cellular stress and remodeling the intracellular structure for cell differentiation. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorders.
The cellular catabolic process in which cells digest parts of their own cytoplasm; allows for both recycling of macromolecular constituents under conditions of cellular stress and remodeling the intracellular structure for cell differentiation. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
cardiolipin peroxidation is a subtype of phospholipid oxidation: The degradation of cardiolipin caused by an oxidative attack from free radicals.
phospholipid peroxidation is a subtype of lipid oxidation: The degradation of phospholipids caused by an oxidative attack from free radicals.
A process that stops, prevents, or reduces the frequency, rate or extent of phospholipid degradation. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (latent).
negative regulation of phospholipid degradation [Phospholipidosis (latent)]
Increasing glucagon level is a subtype of increasing quantity: A process that changes the amount of glucagon level to be higher.
Increasing glucagon level is a subtype of increasing quantity: A process that changes the amount of glucagon level to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Increasing glucagon level [mitochondrial disorder]
Glucose homeostasis imbalance is a subtype of chemical homeostasis imbalance: A process that becomes lacking a glucose homeostastasis balance. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
glucose homeostasis imbalance [mitochondrial disorder]
Increasing glucose level is a subtype of increasing quantity: A process that changes the amount of glucose level to be higher.
Increasing glucose level is a subtype of increasing quantity: A process that changes the amount of glucose level to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
increasing glucose level [mitochondrial disorder]
Furthermore, high glucose levels promote ROS overproduction within hepatocytes, thus favoring oxidative stress and mitochondrial dysfunction.
Consistent with this, high glucose induces mitochondrial fragmentation, ROS production, loss of mitochondrial membrane potential, and ATP depletion in several rodent and human cell models.
Decreasing glucose level is a subtype of decreasing quantity: A process that changes the amount of glucose level to be lower.
Decreasing glucose level is a subtype of decreasing quantity: A process that changes the amount of glucose level to be lower. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Decreasing glucose level [mitochondrial disorder]
Hyperfunction of gluconeogenesis is a subtype of hyperfunction of biosynthesis: A process that performs an excessive gluconeogenesis.
Decreasing glutathione level is a subtype of decreasing quantity: A process that changes the amount of glutathione level to be lower.
Negative regulation of glutathione transport is a subtype of negative regulation of transport: Any process that stops, prevents, or reduces the frequency, rate or extent of the directed movement of glutathione into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
Negative regulation of glutathione transport
Increasing ketone body level is a subtype of increasing quantity: A process that changes the amount of ketone body level to be higher.
Increasing ketone body level is a subtype of increasing quantity: A process that changes the amount of ketone body level to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Increasing ketone body level [mitochondrial disorder]
Any process that results in induction of genomic instability.
Gemfibrozil (GEM) is a clofibrate analog used to treat moderate to severe hypertriglyceridemias. In lab animals, GEM causes peroxisome proliferation, an effect that has been associated with hepatocarcinogenesis in rats. In humans, hepatobiliary disorders, but not carcinogenesis, have been associated with GEM therapy.
Connexin signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by connexin. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Connexin signaling (primitive) [hepatocarcinogenesis]
It suggested that decrease of expression and lacking of function of CX32, CX43 might keep close relationship with liver hepatocarcinogenesis.
Cx32 facilitated HCC progression by blocking chemotherapy-induced apoptosis in vitro and in vivo via interacting with Src and thus promoting the phosphorylation of EGFR, subsequently activating the EGFR signaling pathway.
Any process that stops, prevents, or reduces the frequency, rate or extent of connexin signaling, a series of reactions mediated by connexin. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
negative regulation of connexin signaling [hepatocarcinogenesis]
The results indicated that carcinogenesis and development of human hepatocellular carcinoma related with the abnormal expression of cx genes and disorder of its signal transduction pathway, such as decrease of (Ca(2+))i, post-translation phosphorylation on tyrosine of Cx proteins which led to a dramatic disruption of GJIC. It suggested that decrease of expression and lacking of function of CX32, CX43 might keep close relationship with liver hepatocarcinogenesis.
Increasing cholesterol level is a subtype of increasing quantity: A process that changes the amount of cholesterol level to be higher.
Increasing cholesterol level is a subtype of increasing quantity: A process that changes the amount of cholesterol level to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Increasing cholesterol level [mitochondrial disorder]
Bellanti et al. showed through targeted lipidomic analysis that rats fed diets rich in cholesterol exhibited increased toxic hepatic triol, which induces apoptosis and impaired mitochondrial respiration in vitro. Gan et al. showed that mitochondrial-free cholesterol deposition causes hepatocyte apoptosis and necrosis through c-Jun N-terminal kinase (JNK) activation, associated with increased high-mobility group box 1 (HMGB1), and cytolytic effects on neighboring hepatocytes driven by Toll-like receptor 4 (TLR4). Moreover, mitochondrial-free cholesterol sensitizes liver cells to TNFα- and Fas-mediated steatohepatitis and causes mitochondrial-reduced glutathione (mGSH) depletion, which is also reported in animal models and patients with NASH.
Increasing triol level is a subtype of increasing quantity: A process that changes the amount of triol level to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Increasing triol level [mitochondrial disorder]
cisplatin resistance (process) is a subtype of decreasing sensitivity: A process that changes the sensitivity to cisplatin to be lower.
drug resistance (process) is a subtype of decreasing sensitivity: A process that changes the sensitivity to the drug to be lower.
diacylglycerol accumulation is a subtype of accumulation of substances in a biological object: A process that keeps diacylglycerol in an organism, tissue, organelle, or cell.
diacylglycerol accumulation is a subtype of accumulation of substances in a biological object: A process that keeps diacylglycerol in an organism, tissue, organelle, or cell. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
diacylglycerol accumulation [mitochondrial disorder]
Saturated fats promote fatty liver and accumulation of lipotoxic byproducts including ceramides and diacylglycerols is associated with hepatic inflammation and mitochondrial ROS production resulting in liver cell death.
As a result, fatty acids especially diacylglycerol and ceramide may excessively accumulate in liver tissue. Previous report has shown that diacylglycerol can activate PKC to impair insulin signal pathway.
Negative regulation of sphingolipid metabolic process is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of sphingolipid metabolic process.
Negative regulation of sphingolipid metabolic process
Negative regulation of sphingolipid metabolic process is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of sphingolipid metabolic process. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Negative regulation of sphingolipid metabolic process [hepatocarcinogenesis]
The disruption of the phospholipid and n-6 fatty acid metabolic pathway, producing changes in the level of C20:4ω6, appears to be critical with respect to cancer promotion, especially at low dietary levels of FB1, where cancer promotion is effected in the absence of apoptosis and the disruption of the sphingolipid metabolic pathway.
Disruption of sphingolipid metabolism and stimulation of DNA synthesis by fumonisin B1. A molecular mechanism for carcinogenesis associated with Fusarium moniliforme. These results establish that fumonisin B1 is mitogenic via accumulation of sphingoid bases rather than inhibition of complex sphingolipid biosynthesis per se.
ceramide accumulation is a subtype of accumulation of substances in a biological object: A process that keeps ceramide in an organism, tissue, organelle, or cell. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
ceramide accumulation [mitochondrial disorder]
As a result, fatty acids especially diacylglycerol and ceramide may excessively accumulate in liver tissue. Moreover, ceramide also activates PKC to suppress protein kinase AKT and further inhibits insulin signal pathway.
sorafenib resistance (process) is a subtype of decreasing sensitivity: A process that changes the sensitivity to sorafenib to be lower.
Telomerase reverse transcriptase gene mutation is a subtype of changing an operand: A process that changes the nucleotide sequence of Telomerase reverse transcriptase gene randomly and permanently.
Telomerase reverse transcriptase gene mutation
Increasing triol level is a subtype of increasing quantity: A process that changes the amount of triol level to be higher.
Methapyrilene hydrochloride [hepatocarcinogenesis]
Panadiplon (U-78875) is an anxiolytic drug with a novel chemical structure that is not closely related to other drugs of this type. (by Wikipedia)
The relevance of pyrethrins-induced rat liver tumors to human health was assessed by using the 2006 International Programme on Chemical Safety Human Relevance Framework. It is concluded that pyrethrins do not pose a hepatocarcinogenic hazard for humans.
Fialuridine, or 1-(2-deoxy-2-fluoro-1-D-arabinofuranosyl)-5-iodouracil (FIAU), is a nucleoside analogue that was investigated as a potential therapy for hepatitis B virus infection. (by Wikipedia)
Increasing fructose level is a subtype of increasing quantity: A process that changes the amount of fructose level to be higher.
Increasing fructose level is a subtype of increasing quantity: A process that changes the amount of fructose level to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Increasing fructose level [mitochondrial disorder]
In addition to its ability to promote de novo lipogenesis and block β-oxidation of fatty acids, fructose consumption seems to cause a drop in ATP and an elevation of uric acid, which can further induce mitochondrial oxidative stress. Moreover, a diet rich in fructose is associated with increased oxidative mtDNA lesions in rat liver coupled with reduced mitochondrial repair capacity and rats consuming a diet high in fat and rich in fructose have increased hepatocyte damage, inflammation, and lipid peroxidation coupled with impaired mitochondrial respiration and activity.
Hypofunction of mitochondrial repair is a subtype of hypofunctioning: A process that performs a decreased or insufficient mitochondrial repair. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Hypofunction of mitochondrial repair [mitochondrial disorder]
Moreover, a diet rich in fructose is associated with increased oxidative mtDNA lesions in rat liver coupled with reduced mitochondrial repair capacity and rats consuming a diet high in fat and rich in fructose have increased hepatocyte damage, inflammation, and lipid peroxidation coupled with impaired mitochondrial respiration and activity.
Increasing uric acid level is a subtype of increasing quantity: A process that changes the amount of uric acid level to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Increasing uric acid level [mitochondrial disorder]
Any process that activates or decreases the frequency, rate or extent of mitophagy.
The orderly movement of a macrophage from one site to another. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
macrophage migration [mitochondrial disorder]
malondialdehyde [mitochondrial disorder]
Disruption of ER-mitochondria contact sites is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of ER-mitochondria contact site.
disruption of ER-mitochondria contact sites
Disruption of ER-mitochondria contact sites is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of ER-mitochondria contact site. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Disruption of ER-mitochondria contact sites [mitochondrial disorder]
Therefore, disruption of ER-mitochondria contact sites could exacerbate hepatic lipid accumulation and miscommunication between organelles appears to be related to the pathology of hepatic metabolic diseases.
Increasing mtDNA level is a subtype of decreasing quantity: A process that changes the amount of glycogen level to be higher.
glutathione transport from cytoplasm into mitochondria is a subtype of glutathione transport: A process that exports the glutathione from cytoplasm into mitochondria.
glutathione transport from cytoplasm into mitochondria
Indeed, increased mitochondrial cholesterol during NAFLD could reduce mitochondrial transport of GSH, thus inducing lower mtGSH levels and oxidative stress (Fig. 4).
Negative regulation of glutathione transport into mitochondria is a subtype of negative regulation of transport: Any process that stops, prevents, or reduces the frequency, rate or extent of the directed movement of glutathione into mitochondria by means of some agent such as a transporter or pore.
Negative regulation of glutathione transport into mitochondria
Negative regulation of glutathione transport into mitochondria is a subtype of negative regulation of transport: Any process that stops, prevents, or reduces the frequency, rate or extent of the directed movement of glutathione into mitochondria by means of some agent such as a transporter or pore. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Negative regulation of glutathione transport into mitochondria [mitochondrial disorder]
The directed movement of long-chain fatty acids into a mitochondria. A long-chain fatty acid is a fatty acid with a chain length between C13 and C22.
long-chain fatty acid import into mitochondria
The directed movement of long-chain fatty acids into a mitochondria. A long-chain fatty acid is a fatty acid with a chain length between C13 and C22. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
long-chain fatty acid import into mitochondria [mitochondrial disorder]
Whereas SCFAs and MCFAs freely enter mitochondria, the entry of LCFAs within these organelles requires different enzymes such as long‐chain acyl‐CoA synthetase (ACS), CPT1, and CPT2. For instance, LCFA‐mediated PPARα activation increases the expression of the mitochondrial enzymes CPT1 and medium‐chain acyl‐CoA dehydrogenase (MCAD).
Hypofunction of mitochondrial repair is a subtype of hypofunctioning: A process that performs a decreased or insufficient mitochondrial repair.
Increase in mitochondrial calcium level is a subtype of increase in calcium level: A process that changes the calcium ion concentration within a mitochondria to be higher.
Increase in mitochondrial calcium level is a subtype of increase in calcium level: A process that changes the calcium ion concentration within a mitochondria to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Increase in mitochondrial calcium level [mitochondrial disorder]
Mitochondrial cholesterol storage is a subtype of cholesterol storage: A process that keeps cholesterol in the mitochondria.
Mitochondrial cholesterol storage is a subtype of cholesterol storage: A process that keeps cholesterol in the mitochondria. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
mitochondrial cholesterol storage [mitochondrial disorder]
Bellanti et al. showed through targeted lipidomic analysis that rats fed diets rich in cholesterol exhibited increased toxic hepatic triol, which induces apoptosis and impaired mitochondrial respiration in vitro. Gan et al. showed that mitochondrial-free cholesterol deposition causes hepatocyte apoptosis and necrosis through c-Jun N-terminal kinase (JNK) activation, associated with increased high-mobility group box 1 (HMGB1), and cytolytic effects on neighboring hepatocytes driven by Toll-like receptor 4 (TLR4). Hepatocyte free cholesterol lipotoxicity results from JNK1-mediated mitochondrial injury and is HMGB1 and TLR4-dependent. Moreover, mitochondrial-free cholesterol sensitizes liver cells to TNFα- and Fas-mediated steatohepatitis and causes mitochondrial-reduced glutathione (mGSH) depletion, which is also reported in animal models and patients with NASH. Thus, accumulating evidences suggest that cholesterol overload in mitochondria induces redox imbalances leading to oxidative stress and cell death associated with steatohepatitis.
Negative regulation of mitochondrial respiratory chain complex I subunit phosphorylation is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of mitochondrial respiratory chain complex I subunit phosphorylation.
Negative regulation of mitochondrial respiratory chain complex I subunit phosphorylation
Negative regulation of phosphorylation is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of phosphorylation.
mitochondrial respiratory chain complex I subunit phosphorylation
Mitochondrial dysfunction is a subtype of dysfunctioning: A process that performs an abnormal and incomplete mitochondrial function. This entity is a specific course-dependent process. This process can constitute the hepatocarcinogenesis.
mitochondrial dysfunction [hepatocarcinogenesis]
Just like in NASH, oxidative stress, mitochondrial dysfunction, and oxidized mtDNA also contribute to the progression of HCC through influences on inflammation, cell death, and ER stress. Among these, mitochondrial dysfunction is linked to cancer progression through increased ROS production, impaired mitochondrial respiration, ER stress, and alteration of nutrient metabolism.
Dysregulation of mitochondrion organization is a subtype of malfunctioning of controlling: A process that cannot perform a regulation of mitochondrion organization appropriately or cannot realize it at all.
mitochondrial membrane morphology changes is a subtype of mitochondria morphology changes: A process that changes the morphology of the mitochondrial membrane.
mitochondrial membrane morphology changes
Increasing mitochondrial membrane potential is a subtype of increasing membrane potential: A process that changes the electrical potential of a mitochondrial membrane to be higher.
Increasing mitochondrial membrane potential
Increasing membrane potential is a subtype of changing membrane potential: A process that changes the electrical potential across a membrane to be higher.
Metalloprotease activation is a subtype of activating: A process that changes the activity of the metalloprotease to be higher.
Wang et al demonstrated that BRD4 is able to promote HCC cell migration and invasion in vitro and that BRD4 activity is mediated by HH signalling through the metalloproteases MMP - 2 and MMP - 9.
Negative regulation of methionine metabolic process is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of methionine metabolic process.
Negative regulation of methionine metabolic process
Negative regulation of methionine metabolic process is a subtype of negative regulation process: A process that stops, prevents, or reduces the frequency, rate or extent of methionine metabolic process. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Negative regulation of methionine metabolic process [hepatocarcinogenesis]
In mammals, the liver plays a central role in methionine metabolism, and this essential function is lost in the progression from liver cirrhosis to hepatocarcinoma. Methylthioadenosine phosphorylase (MTAP) is a key enzyme in the methionine and adenine salvage pathways. Interestingly, MTAP gene expression was also impaired in the liver of CCl4-cirrhotic rats and cirrhotic patients.
Methylthioadenosine phosphorylase (MTAP) is a key enzyme in the methionine and adenine salvage pathways. In mammals, the liver plays a central role in methionine metabolism, and this essential function is lost in the progression from liver cirrhosis to hepatocarcinoma. Interestingly, MTAP gene expression was also impaired in the liver of CCl4-cirrhotic rats and cirrhotic patients.
phospholipid peroxidation is a subtype of lipid oxidation: The degradation of phospholipids caused by an oxidative attack from free radicals. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
phospholipid peroxidation [mitochondrial disorder]
Phospholipid peroxidation is considered an important contributing factor in mitochondrial dysfunction in several physiopathological conditions as well as during the aging process. In fact, phospholipid peroxidation alters the structural organization of the mitochondrial bilayer, perturbing membrane fluidity and permeability.
Lipoperoxidation is a subtype of lipid oxidation: The degradation of lipids caused by an oxidative attack from free radicals. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
They showed that DEN increased lipid peroxidation in studies performed. This may increase the tumour. Lipid peroxidation produces a wide variety of oxidation products, such as malondialdehyde (MDA), propanal, hexanal, and 4-hydroxy nonanal (4-HNE). MDA appears to be the most mutagenic product of lipid peroxidation, but 4-HNE is most toxic.
Any process that results in a change in state of redox.
Increasing leptin level is a subtype of increasing quantity: A process that changes the amount of leptin level to be higher.
Increasing leptin level is a subtype of increasing quantity: A process that changes the amount of glucagon level to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
increasing leptin level [mitochondrial disorder]
Tumor malignancy alteration is a subtype of changing quality of tumor: A process that changes the quality of the tumors to progress, invade surrounding tissues or metastasize. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
tumor malignancy alteration [hepatocarcinogenesis]
Tumor malignancy is characterized by invasiveness and metastasis, which occur through EMT.
Malfunctioning of centrosome duplication is a subtype of malfunctioning process: A process that cannot perform centrosome duplication appropriately or cannot realize it at all.
malfunctioning of centrosome duplication
On the other hand, hypoxia-inducing factor 1α (HIF-1α) proved to enhance the EMT of HCC cells; its expression correlates with IL-1β-related inflammation intensity.
reduced oxygenation of body tissues resulting in the decreased pressure of this component of body gases; commonly due to hypoxemia This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
In HCC cells, epithelial mesenchymal transition (EMT) can be induced under hypoxia condition through the activation of Wnt/β-catenin pathway or PI3K/AKT pathway. Hypoxia-induced up-regulation of PDGF-BB in hepatic satellite cells activated the PI3K/Akt pathway in HCC cells and enhanced cell proliferation, migration, and resistance to bile acid-induced apoptosis. Hypoxia-activated YAP and TGF-α/EGFR pathways blunted the response of HCC cells to sorafenib.
In this study, we observed that hypoxia-induced downregulation of UHRF1 contributes to the induction of the epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma cells.
Hypoxia stimulates c-MET overexpression in HCC cells. Although the hypoxia microenvironment may induce EMT, the hypoxia-related EMT cascade cannot be activated without the simultaneous activation of actin cytoskeleton remodeling via the Wnt/β-catenin pathway. Hypoxia-related EMT is also linked with the aberrant hedgehog pathway which plays an important role in maintaining the stem cell capacity of tumor cells. Hypoxia could also promote the EMT of HCC cells via Twist1 upregulation.
Dysregulation of immune balance is a subtype of malfunctioning of controlling: A process that cannot perform a regulation of immune balance appropriately or cannot realize it at all.
Hypofunction of immune response to tumor cell is a subtype of hypofunctioning: A process that performs a decreased or insufficient immune response to tumor cell. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
hypofunction of immune response to tumor cell [hepatocarcinogenesis]
In the late stage, a series of oncogenic signaling pathways activated by HBV result in immune escape, and promotes the finally developing HCC. The increased Tregs not only suppressed HBV antigen-specific immune responses, but also suppressed HCC tumor antigen-specific immune responses.
The orderly movement of a regulatory T cell from one site to another.
protooncogene activation is a subtype of molecular activation: A process that changes the activity of the protooncogene to be higher.
Protooncogene activation is a subtype of molecular activation: A process that changes the activity of the protooncogene to be higher. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
protooncogene activation [hepatocarcinogenesis]
Increasing production amount of reactive aldehyde is a subtype of increasing quantity: A process that changes the production amount of reactive aldehyde to be higher.
increasing production amount of reactive aldehyde
reactive aldehyde [mitochondrial disorder]
4-hydroxynonenal [mitochondrial disorder]
Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stress acting at the endoplasmic reticulum. ER stress usually results from the accumulation of unfolded or misfolded proteins in the ER lumen. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
response to endoplasmic reticulum stress [hepatocarcinogenesis]
Increasing uric acid level is a subtype of increasing quantity: A process that changes the amount of uric acid level to be higher.
Hypofunction of immune response to tumor cell is a subtype of hypofunctioning: A process that performs a decreased or insufficient immune response to tumor cell.
hypofunction of immune response to tumor cell
Negative regulation of antioxidant enzyme activation is a subtype of Negative regulation of enzyme activation: A process that stops, prevents, or reduces the frequency, rate or extent of antioxidant enzyme activation.
negative regulation of antioxidant enzyme activation
Increasing damaged mitochondria is a subtype of decreasing quantity: A process that changes the amount of damaged mitochondria to be higher.
The process that results in the movement of inflammatory DAMPs from the mitochondria. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
release of inflammatory DAMPs [mitochondrial disorder]
Prevention of autophagy further leads to accumulation of damaged mitochondria that can release inflammatory DAMPs and cytochrome C to promote cell death, and/or exacerbate endoplasmic reticulum (ER) stress. Reduced mitophagy results in the accumulation of severely damaged mitochondria, leading to cell necrosis releasing mitochondrial damage-associated molecular patterns (DAMPs) that can promote liver inflammation and NASH development. Mitochondrial DAMPs (MTDs) activate pattern recognition receptors (PRRs), such as Toll-like receptor (TLR)9.
Any process that stops, prevents, or reduces the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of ROS. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
negative regulation of ROS formation [hepatocarcinogenesis]
The elimination of DNA damage or blockage of ROS production significantly reduced the expression of NOXA, and thereby attenuated apoptosis and reduced growth inhibition of liver cancer cells.
Malfunctioning of cytokinesis is a subtype of malfunctioning process: A process that cannot perform cytokinesis appropriately or cannot realize it at all.
Increasing blood glucose level is a subtype of increasing concentration: A process that changes the blood glucose concentration in the blood to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
increasing blood glucose level [mitochondrial disorder]
On the whole, the data indicate that increased flux through anaplerotic/cataplerotic pathways not only contributes to dysregulation of downstream nutrients (e.g., glycemia and lipidemia), but also triggers oxidative metabolism and altered antioxidant capacity that contribute to the development of oxidative stress, inflammation, and insulin resistance (Figure 8B and Supplemental Table 2).
Cellular damage is a subtype of damaging: A process that injuries the structure of the cell as the direct or indirect result of an external force. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
The process in which the anatomical structures of the nodule are generated and organized. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
At 10 months after the injection, nodules consisting of highly dysplastic malignant cells were observed in liver of Pim-3 transgenic mice and to a lesser extent in WT mice (Figure 5a). The produced factors can drive compensatory and aberrant proliferation of surviving hepatocytes and development of pre-malignant dysplastic nodules that form the nucleus of neoplastic lesions.
Hepatocyte regeneration is a subtype of changing material: The regrowth of lost or destroyed hepatocytes.
Increasing lipid is a subtype of increasing quantity: A process that changes the amount of lipid to be larger. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
Increasing lipid concentration in blood is a subtype of increasing concentration: A process that changes the lipid concentration in the blood to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
increasing lipid concentration [mitochondrial disorder]
Tumor malignancy alteration is a subtype of changing quality of tumor: A process that changes the quality of the tumors to progress, invade surrounding tissues or metastasize.
A mebrane potential which is relatively high.
Increasing cholesterol concentration in blood is a subtype of increasing lipid concentration in blood: A process that changes the cholesterol concentration in the blood to be higher.
Increasing cholesterol concentration in blood
Increasing lipid concentration in blood is a subtype of increasing concentration: A process that changes the lipid concentration in the blood to be higher.
Increasing cholesterol concentration in blood is a subtype of increasing lipid concentration in blood: A process that changes the cholesterol concentration in the blood to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Increasing cholesterol concentration in blood [mitochondrial disorder]
More precisely, dietary-induced hypercholesterolemia causes oxidative stress, loss of mitochondrial membrane potential, reduction in ATP content, loss of mitochondrial cristae, and hepatic steatosis in mice.
The movement of an endothelial progenitor cell (EPC) within or between different tissues and organs of the body.
endothelial progenitor cell mobilization
neovascularization is a subtype of biological structure formation: A process that constructs an alternate blood vessels.
Enzyme production is a subtype of protein production: A process that makes existent of enzyme due to biosynthesis, secretion, or membrane trafficking, resulting in an increase in its levels.
iron metabolic dysfunction is a subtype of Metabolic dysfunctioning: A process that performs an abnormal and incomplete energy metabolic function.
iron metabolic dysfunction is a subtype of Metabolic dysfunctioning: A process that performs an abnormal and incomplete energy metabolic function. This entity is a specific course-dependent process. This process can constitute the course of hepatocarcinogenesis.
iron metabolic dysfunction [hepatocarcinogenesis]
These in vivo results confirmed that PVT1 played a crucial role on regulating tumor growth and iron metabolism disorder in HCC, which may be associated with the modulation of miR-150/HIG2 signaling.
Increasing iron uptake level is a subtype of increasing quantity: A process that changes the iron uptake level to be larger.
Hypofunction of heme biosynthesis is a subtype of hypofunction of biosynthesis: A process that performs a decreased or insufficient heme biosynthesis.
Increasing long-chain free fatty acid level is a subtype of increasing quantity: A process that changes the amount of long-chain free fatty acid level to be higher.
Increasing long-chain free fatty acid level
Increasing long-chain free fatty acid level is a subtype of increasing quantity: A process that changes the amount of long-chain free fatty acid level to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Increasing long-chain free fatty acid level [mitochondrial disorder]
Long-chain free fatty acids which accumulate in nonalcoholic fatty liver are considered the initial source of this ROS damaging cycle. These compounds have been shown to promote ROS production in mitochondria, although the mechanism(s) underlying this effect is still unclear.
Increasing saturated fatty acid level is a subtype of increasing quantity: A process that changes the amount of saturated fatty acid level to be higher.
Increasing saturated fatty acid level is a subtype of increasing quantity: A process that changes the amount of saturated fatty acid level to be higher. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
Increasing saturated fatty acid level [mitochondrial disorder]
Saturated fats promote fatty liver and accumulation of lipotoxic byproducts including ceramides and diacylglycerols is associated with hepatic inflammation and mitochondrial ROS production resulting in liver cell death. Moreover, in vitro treatment of liver cells with saturated fatty acids (palmitic and stearic acids) reproduces mitochondrial dysfunction found in NASH, including decreasing cellular ATP content and mtDNA-encoded oxidative phosphorylation (OXPHOS) subunit expression, coupled with increased oxidative stress.
saturated fatty acid [mitochondrial disorder]
Hypofunction of phospholipid degradation is a subtype of hypofunction of decomposing: A process that performs a decreased or insufficient phospholipid degradation. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis (latent).
hypofunction of phospholipid degradation [Phospholipidosis(latent)]
1,2-dichloropropane [hepatocarcinogenesis]
Hypofunction of 17β-Estradiol metabolic process is a subtype of hypofunction of metabolism: A process that performs a decreased or insufficient 17β-Estradiol metabolic process.
Hypofunction of 17β-Estradiol metabolic process
Liver cancer dependent molecule is a subtype of toxic course dependent chemical entity. This gene can participate in the course of Liver cancer as a gene product. Gene profile:canonical/in vitro/Hepatocyte/
liver cancer dependent molecule (canonical)
A series of molecular signals mediated by AGGF1 (angiogenic factor with G-patch and FHA domains 1).
AGGF1 signaling (primitive) is a subtype of signaling [biological]: A process that in which a signal is transmitted by AGGF1.
AMPK(canonical) [mitochondrial disorder]
Liver cancer dependent molecule is a subtype of toxic course dependent chemical entity. This gene can participate in the course of Liver cancer as a gene product. Gene profile:Mouse
liver cancer dependent molecule (mouse in vitro)
FOXO1 (canonical)[mitochondrial disorder]
HIF1A(canonical) [mitochondrial disorder]
HNF4A (canonical) [hepatocarcinogenesis]
KIAA0101 tv2 (predicted)(human) [hepatocarcinogenesis]
NDUFA12 (human) [mitochondrial disorder]
NDUFA12 - inactive form (human)[mitochondrial disorder]
These results were repeated and confirmed by generating phosphorylation defective forms of these 5 CI subunits through substitutions of Serine/Threonine (S/T) residues with Alanine (A) on either Cdk1 optimal or minimal consensus motifs (T383 on NDUFV1, S105 on NDUFV3, S364 on NDUFS2, S55/S29/T5 on NDUFB6 and T142/T120 on NDUFA12). The mutation of Cdk1 consensus motifs severely diminished their phosphorylation (Figure 3F).
NDUFA12 inactivation is a subtype of molecular inactivation: A process that changes the activity of the NDUFA12 (NADH:ubiquinone oxidoreductase core subunit A12) to be lower. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
NDUFA12 inactivation [mitochondrial disorder]
NDUFB6 - inactive form (human)[mitochondrial disorder]
NDUFB6 inactivation is a subtype of molecular inactivation: A process that changes the activity of the NDUFB6 (NADH:ubiquinone oxidoreductase core subunit B6) to be lower. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
NDUFB6 inactivation [mitochondrial disorder]
NDUFS2 - inactive form (human)[mitochondrial disorder]
NDUFS2 inactivation is a subtype of molecular inactivation: A process that changes the activity of the NDUFS2 (NADH:ubiquinone oxidoreductase core subunit S2) to be lower. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
NDUFS2 inactivation [mitochondrial disorder]
NDUFV1 - inactive form (human)[mitochondrial disorder]
NDUFV1 inactivation is a subtype of molecular inactivation: A process that changes the activity of the NDUFV1 (NADH:ubiquinone oxidoreductase core subunit V1) to be lower. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
NDUFV1 inactivation [mitochondrial disorder]
NDUFV3 - inactive form (human)[mitochondrial disorder]
NDUFV3 inactivation is a subtype of molecular inactivation: A process that changes the activity of the NDUFV3 (NADH:ubiquinone oxidoreductase core subunit V3) to be lower. This entity is a specific course-dependent process. This process can constitute the course of mitochondrial disorder.
NDUFV3 inactovation [mitochondrial disorder]
NRF2(canonical) [mitochondrial disorder]
PCK1 - inactive form (predicted)(human) [mitochondrial damage]
PPARA(canonical) [mitochondrial disorder]
PROM1 - activation state (human)[hepatocarcinogenesis]
bis(2-ethylhexyl) phthalate [hepatocarcinogenesis]
The process that results in the movement of inflammatory DAMPs from the mitochondria.
Tumor malignancy alteration is a subtype of changing quality: A process that changes the tumor malignancy. Changing quality of tumor is a subtype of changing quality: A process that changes the quailty of tumor cells.
central nervous system sphingomyelin homeostasis imbalance [Niemann Pick Disease Type A]
The chemical reactions and pathways resulting in the formation of phospholipids, any lipid containing phosphoric acid as a mono- or diester. This entity is a specific course-dependent process. This process can constitute the course of Phospholipidosis(latent).
phospholipid biosynthetic process [Phospholipidosis(latent)]
ATP-binding cassette (ABC) transporter superfamily
6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime
One known target involved in FA metabolism is HMG-CoA synthetase 2 (HMGCS2), the rate-limiting step in ketogenesis. Upon activation, SIRT3 deacetylates and activates HMGCS2 to increase ketone body synthesis The importance of this regulation in hepatic and whole-body lipid metabolism has not been characterized; however, absence of HMGCS2 causes hypoketotic hypoglycemia and fatty liver in humans fed low-carbohydrate diets, suggesting that this enzyme plays a major role in FA disposal and linking FA catabolism to gluconeogenesis.
An aminoquinoline that is quinoline which is substituted at position 4 by a [5-(diethylamino)pentan-2-yl]amino group at at position 7 by chlorine. It is used for the treatment of malaria, hepatic amoebiasis, lupus erythematosus, light-sensitive skin eruptions, and rheumatoid arthritis.
The olfactory organ of vertebrates, consisting of nares, olfactory epithelia and the structures and skeletal framework of the nasal cavity.
Organ that is the specialized structure of the face that contains olfactory neurons. The peripheral olfactory organ is paired[ZFA:0000047].
a protuberance in vertebrates that houses the nostrils, or nares, which admit and expel air for respiration in conjunction with the mouth. Behind the nose are the olfactory mucosa and the sinuses. Behind the nasal cavity, air next passes through the pharynx, shared with the digestive system, and then into the rest of the respiratory system. In humans, the nose is located centrally on the face; on most other mammals, it is on the upper tip of the snout[WP]. GO: The nose is the specialized structure of the face that serves as the organ of the sense of smell and as part of the respiratory system. Includes the nasi externus (external nose) and cavitas nasi (nasal cavity)[Wikipedia:Nose].
the organ that is specialized for smell and is part of the respiratory system
the structure of the nose varies across vertebrates. In tetrapods the nose is part of the respiratory system.[PMID:25312359]
An organ that is capable of transducing sensory stimulus to the nervous system.
Any hollow cylindrical anatomical structure containing a lumen through which substances are transported.
not every anatomical conduit is a tube - for example, a bone foramen is an opening in the bone, and there is no distinct separate tube structure. Tubes may transport large mixed objects (for example, a bolus of food in the digestive tube) or they may transport the secretions of a single gland (for example, gland ducts)
Muscular duct that propels urine from the kidneys to the urinary bladder, or related organs.
Anatomical structure consisting of long narrow duct which carries urine from the kidney to the urinary bladder.[AAO]
The duct of amniotes that carries urine from a metanephric kidney to the urinary bladder. [Bemis_WE, Functional_Anatomy_of_the_Vertebrates:_An_Evolutionary_Perspective, Glossary_G-29, Grande_L, Liem_KF, Third_Edition_(2001)_Orlando_Fla.:_Harcourt_College_Publishers, Walker_WF][VHOG]
The first embryonic hint of a metanephros is the formation of the metanephric duct that appears as a ureteric diverticulum arising at the base of preexisting mesonephric duct. The ureteric diverticulum grows dorsally into the posterior region of the nephric ridge. Here it enlarges and stimulates the growth of metanephric tubules that come to make up the metanephric kidney. The metanephros becomes the adult kidney of amniotes, and the metanephric duct is usually called the ureter.[well established][VHOG]
in humans, consists of adventitial, muscular and mucoa layers
A tubular structure that transports secreted or excreted substances.
A subdivision of the digestive tract that connects the small intestine to the cloaca or anus. Lacks or has few villi[Kardong].
Material anatomical entity that is a single connected structure with inherent 3D shape generated by coordinated expression of the organism's own genome.
Anatomical structure that performs a specific function or group of functions [WP].
Organs are commonly observed as visibly distinct structures, but may also exist as loosely associated clusters of cells that work together to perform a specific function or functions.
A multicellular structure that is a part of an organ.
currently defined in a very broad sense, may be replaced by more specific classes in the future
Segment of the alimentary canal extending from the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine
The pair of anatomical structures comprised of a left lung and right lung.
Organ that functions in gaseous exchange between an organism and its environment. In plants, microorganisms, and many small animals, air or water makes direct contact with the organism's cells or tissue fluids, and the processes of diffusion supply the organism with dioxygen (O2) and remove carbon dioxide (CO2). In larger animals the efficiency of gaseous exchange is improved by specialized respiratory organs, such as lungs and gills, which are ventilated by breathing mechanisms.
A fluid that is composed of blood plasma and erythrocytes.
This class excludes blood analogues, such as the insect analog of blood. See UBERON:0000179 haemolymphatic fluid.
A complex mixture of cells suspended in a liquid matrix that delivers nutrients to cells and removes wastes. (Source: BioGlossary, www.Biology-Text.com)[TAO]
Highly specialized circulating tissue consisting of several types of cells suspended in a fluid medium known as plasma.[AAO]
Recent findings strongly suggest that the molecular pathways involved in the development and function of blood cells are highly conserved among vertebrates and various invertebrates phyla. (...) There is now good reason to believe that, in vertebrates and invertebrates alike, blood cell lineages diverge from a common type of progenitor cell, the hemocytoblast.[well established][VHOG]
Circulating fluid that is part of the hemolymphoid system. Blood, lymph, interstitial fluid or its analogs.
Material anatomical entity in a gaseous, liquid, semisolid or solid state; produced by anatomical structures or derived from inhaled and ingested substances that have been modified by anatomical structures as they pass through the body.
Non-material anatomical entity of three dimensions, that is generated by morphogenetic or other physiologic processes; is surrounded by one or more anatomical structures; contains one or more organism substances or anatomical structures.
Multicellular, connected anatomical structure that has multiple organs as parts and whose parts work together to achieve some shared function.
Multicellular anatomical structure that consists of many cells of one or a few types, arranged in an extracellular matrix such that their long-range organisation is at least partly a repetition of their short-range organisation.
Portion of tissue, that consists of one or more layers of epithelial cells connected to each other by cell junctions and which is underlain by a basal lamina. Examples: simple squamous epithelium, glandular cuboidal epithelium, transitional epithelium, myoepithelium[CARO].
The two basic types of metazoan tissue are epithelial and connective. The simplest metazoans, and developmental stages of many primitive invertebrates, consist solely of these two layers. Thus, epithelial and connective tissues may be the primary (original) tissues of metazoans, and both are important in the functional organization of animals.[well established][VHOG]
An expanded region of the vertebrate alimentary tract that serves as a food storage compartment and digestive organ. A stomach is lined, in whole or in part by a glandular epithelium.
Portion of alimentary canal with increased circular and longitudinal smooth muscle. Bounded posteriorly by the pyloric sphincter. Mucosal lining has increased folding.[AAO]
It appears that the stomach has an ancient origin. The stomach first appears in the fish lineage. The prevertebrate chordates do not have a true stomach, whereas the cartilaginous and bony fish do. Although most fish do have a true stomach, some fish species appear to have lost the stomach secondarily. The remaining vertebrate lineages do have a true stomach (at least in the adult animal), although there is great variation in the size and shape of the stomach.[well established][VHOG]
UBERON ontology restricts this to the vertebrate specific structure - see the grouping class 'food storage organ' for analogous structures in other species. Teleosts: Zebrafish is functionally stomach-less, but may retain ontogenic footprint. Although the precise shape and size of the stomach varies widely among different vertebrates, the relative positions of the oesophageal and duodenal openings remain relatively constant. As a result, the organ always curves somewhat to the left before curving back to meet the pyloric sphincter. However, lampreys, hagfishes, chimaeras, lungfishes, and some teleost fish have no stomach at all, with the oesophagus opening directly into the intestine. The gastric lining is usually divided into two regions, an anterior portion lined by fundic glands, and a posterior with pyloric glands. Cardiac glands are unique to mammals, and even then are absent in a number of species. The distributions of these glands vary between species, and do not always correspond with the same regions as in man. Furthermore, in many non-human mammals, a portion of the stomach anterior to the cardiac glands is lined with epithelium essentially identical to that of the oesophagus. Ruminants, in particular, have a complex stomach, the first three chambers of which are all lined with oesophageal mucosa
A myogenic muscular circulatory organ found in the vertebrate cardiovascular system composed of chambers of cardiac muscle. It is the primary circulatory organ. [database_cross_reference: http://orcid.org/0000-0002-6601-2165][database_cross_reference: http://en.wikipedia.org/wiki/Heart]
Taxon notes:" the ascidian tube-like heart lacks chambers....The ascidian heart is formed after metamorphosis as a simple tube-like structure with a single-layered myoepithelium that is continuous with a single-layered pericar- dial wall. It lacks chambers and endocardium.... The innovation of the chambered heart was a key event in vertebrate evolution, because the chambered heart generates one-way blood flow with high pressure, a critical requirement for the efficient blood supply of large-body vertebrates... all extant vertebrates have hearts with two or more chambers (Moorman and Christoffels 2003)" http://dx.doi.org/10.1101/gad.1485706
Anatomical system that consists of the glands and parts of glands that produce endocrine secretions and help to integrate and control bodily metabolic activity.
Anatomical system containing glands which regulates bodily functions though the secretion of hormones.[AAO]
Multicellular organisms have complex endocrine systems, allowing responses to environmental stimuli, regulation of development, reproduction, and homeostasis. Nuclear receptors (NRs), a metazoan-specific family of ligand-activated transcription factors, play central roles in endocrine responses, as intermediates between signaling molecules and target genes. The NR family includes ligand-bound and orphan receptors, that is, receptors with no known ligand or for which there is no ligand Pocket. Understanding NR evolution has been further improved by comparison of several completed genomes, particularly those of deuterostomes and ecdysozoans. In contrast, evolution of NR ligands is still much debated. One hypothesis proposes that several independent gains and losses of ligand-binding ability in NRs occurred in protostomes and deuterostomes. A second hypothesis, pertaining to the NR3 subfamily (vertebrate steroid hormone receptors and estrogen related receptor), proposes that before the divergence of protostomes and deuterostomes, there was an ancestral steroid receptor (AncSR) that was ligand-activated and that orphan receptors secondarily lost the ability to bind a ligand. (...) Our analysis reveals that steroidogenesis has been independently elaborated in the 3 main bilaterian lineages (...).[well established][VHOG]
The brain is the center of the nervous system in all vertebrate, and most invertebrate, animals. Some primitive animals such as jellyfish and starfish have a decentralized nervous system without a brain, while sponges lack any nervous system at all. In vertebrates, the brain is located in the head, protected by the skull and close to the primary sensory apparatus of vision, hearing, balance, taste, and smell[WP].
requires review for applicability to invertebrate structures, e.g. synganglion
Cavitated compound organ which is comprised of gray and white matter and surrounds the cerebral ventricular system.[TAO]
Part of the central nervous system situated within the cranium and composed of both nerve cell bodies and nerve fibers.[AAO]
The part of the central nervous system contained within the cranium, comprising the forebrain, midbrain, hindbrain, and metencephalon. It is derived from the anterior part of the embryonic neural tube (or the encephalon). Does not include retina. (CUMBO)
(...) at some stage of its development, every chordate exhibits five uniquely derived characters or synapomorphies of the group: (...) (4) a single, tubular nerve cord that is located dorsal to the notochord (...) (reference 1); The neural tube is destined to differentiate into the brain and spinal cord (the central nervous system) (reference 2).[well established][VHOG]
The retina is the innermost layer or coating at the back of the eyeball, which is sensitive to light and in which the optic nerve terminates.
This class encompasses a variety of light-detecting structures from different phyla with no implication of homology, from the compound insect eye to the vertebrate camera-type eye (distinct classes are provided for each)
Note that whilst this is classified as an organ, it is in fact more of a unit composed of different structures: in Drosophila, it includes the interommatidial bristle as a part; we consider here the vertebrate eye to include the eyeball/eye proper as a part, with the eye having as parts (when present): eyelids, conjuctiva,
Anatomical system that has as its parts the organs concerned with reproduction.
consider splitting genitalia from reproductive system
Anatomical system which consists of organs and tissues associated with sexual reproduction of the organism.[AAO]
Arguably, one of the most important aspects of urbilaterian organogenesis would have been gonadogenesis, since Urbilateria must have successfully generated gametes and developed a strategy for extrusion and fertilization, in order to be the ancestor of all living Bilateria.[well established][VHOG]
Functional system which consists of structures involved in respiration.
The anatomical system in which the exchange of oxygen and carbon dioxide between the organism and its environment.[AAO]
There is no doubt that the primitive pattern of vertebrate air-breathing is the buccal pulse pump found in actinopterygian fishes.[well established][VHOG]
Anatomical system that has as its parts the organs devoted to the ingestion, digestion, and assimilation of food and the discharge of residual wastes.
An anatomical system consisting of the alimentary canal and digestive glands responsible for intake, absorption, digestion and excretion of food.[AAO]
The renal system in an anatomical system that maintains fluid balance and contributes to electrolyte balance, acid/base balance, and disposal of nitrogenous waste products..
In various sources such as Encyclopedia Britannica, the excretory and urinary systems are indeed the same system (see wikipedia talk page); we merge two BTO classes here
Evolution of vertebrate renal anatomy appears quite conservative when compared, for example, to evolution of respiratory and cardiovascular systems in vertebrates. Major anatomical changes in vertebrates kidneys separate those of birds and mammals from kidneys of lower vertebrates. General increase in animal size from fish to mammals is reflected by an increase in total number of nephrons per kidney, rather than by constant change in tubular dimensions.[well established][VHOG]
In humans, the renal system comprises a pair of kidneys, a pair of ureters, urinary bladder, urethra, sphincter muscle and associated blood vessels
organ system that passes nutrients (such as amino acids and electrolytes), gases, hormones, blood cells, etc. to and from cells in the body to help fight diseases and help stabilize body temperature and pH to maintain homeostasis[WP].
the cardiovascular system and the lymphatic system are parts of the circulatory system
Anatomical system of ion binding, a pumping mechanism, and an efficient vascular system; consisting of the blood, heart, and blood and lymph vessels, respectively.[AAO]
We should divest ourselves of the view that earlier vertebrate groups were 'on their way' to becoming mammals, as clearly they were not such visionaries. Neither were their systems 'imperfect' as earlier anatomists thought. Instead, their circulatory systems served them well to address the ecological demands arising from their lifestyles.[well established][VHOG]
Portion of connective tissue composed of adipocytes enmeshed in areolar tissue
The nervous system is an organ system containing predominantly neuron and glial cells. In bilaterally symmetrical organism, it is arranged in a network of tree-like structures connected to a central body. The main functions of the nervous system are to regulate and control body functions, and to receive sensory input, process this information, and generate behavior [CUMBO].
A regulatory system of the body that consists of neurons and neuroglial cells. The nervous system is divided into two parts, the central nervous system (CNS) and the peripheral nervous system (PNS). (Source: BioGlossary, www.Biology-Text.com)[TAO]
Anatomical system consisting of nerve bodies and nerve fibers which regulate the response of the body to external and internal stimuli.[AAO]
Nervous systems evolved in the ancestor of Eumetazoa.[well established][VHOG]
The central nervous system is the core nervous system that serves an integrating and coordinating function. In vertebrates it consists of the neural tube derivatives: the brain and spinal cord. In invertebrates it includes central ganglia plus nerve cord.
Part of the nervous system which includes the brain and spinal cord.[AAO]
The brain and spinal cord. Kimmel et al, 1995.[TAO]
The central nervous system (CNS) is the part of the nervous system which includes the brain, spinal cord, and nerve cell layer of the retina (CUMBO).
(...) at some stage of its development, every chordate exhibits five uniquely derived characters or synapomorphies of the group: (...) (4) a single, tubular nerve cord that is located dorsal to the notochord (...) (reference 1); The neural tube is destined to differentiate into the brain and spinal cord (the central nervous system) (reference 2); Taken together, our data make a very strong case that the complex molecular mediolateral architecture of the developing trunk CNS (central nervous system), as shared between Platynereis and vertebrates, was already present in their last common ancestor, Urbilateria. The concept of bilaterian nervous system centralization implies that neuron types concentrate on one side of the trunk, as is the case in vertebrates and many invertebrates including Platynereis, where they segregate and become spatially organized (as opposed to a diffuse nerve net). Our data reveal that a large part of the spatial organization of the annelid and vertebrate CNS was already present in their last common ancestor, which implies that Urbilateria had already possessed a CNS (reference 3).[well established][VHOG]
Anatomical system that overlaps the nervous system and is responsible for receiving and processing sensory information.
An early step in the evolution of neural crest, therefore, may have been the origin of a specific dorsal neural cell population contributing to sensory processing; this would predate the divergence of the amphioxus and vertebrate lineages.[well established][VHOG]
Tube that connects the pharynx to the stomach. In mammals, the oesophagus connects the buccal cavity with the stomach. The stratified squamous non-keratinised epithelium lining the buccal cavity is continued through the pharynx down into the oesophagus. The lowest part of the oesophagus (ca. 2 cm) is lined with gastric mucosa and covered by peritoneum. The main body of the oesophagus is lined with small, simple mucous glands. Each gland opens into the lumen by a long duct which pierces the muscularis mucosae (Wilson and Washington, 1989). A sphincter is situated at the point where the oesophagus enters the stomach to prevent gastro-oesophageal reflux, i.e. to prevent acidic gastric contents from reaching stratified epithelia of the oesophagus, where they can cause inflammation and irritation (Wilson and Washington, 1989; Brown et al., 1993).
Anterior end of the alimentary canal lined with smooth muscle. Bounded anteriorly by a constriction in the pharynx. Bounded posteriorly by and increase in circular and/or longitudinal smooth muscle associated with the stomach.[AAO]
The few structural specializations in (adult lampreys) pharynx include complex valves on the external gill openings that direct the tidal flow, and the division of the ancestral pharynx into an oesophagus and a respiratory pharynx.[well established][VHOG]
the terminal portion of the intestinal tube, terminating with the anus
Biological entity that is either an individual member of a biological species or constitutes the structural organization of an individual member of a biological species.
Excretion that is the output of a kidney
kidney excreta from some taxa (e.g. in aves) may not be liquid
Traditional gross anatomy divided the liver into four lobes based on surface features. The falciform ligament is visible on the front (anterior side) of the liver. This divides the liver into a left anatomical lobe, and a right anatomical lobe.
The left lobe is smaller and more flattened than the right. It is situated in the epigastric and left hypochondriac regions. Its upper surface is slightly convex and is moulded on to the diaphragm; its under surface presents the gastric impression and omental tuberosity.
Muscle tissue that consists primarily of skeletal muscle fibers.
Vein that carries blood away from the liver.
Last portion of the large intestine before it becomes the rectum.
Although all vertebrates have a digestive tract and accessory glands, various parts of this system are not necessarily homologous, analogous, or even present in all species. Therefore, broad comparisons can be best made under the listings of headgut, foregut, midgut, pancreas and biliary system, hindgut.[uncertain][VHOG]
A complex network of conduits that begins with the canals of Hering (intralobar bile duct) and progressively merges into a system of interlobular, septal, and major ducts which then coalesce to form the extrahepatic bile ducts, which finally deliver bile to the intestine, and in some species to the gallbladder.
Hollow tree organ, the organ parts of which consist of the bile ducts.[AAO]
The path in many species is as follows: Bile canaliculi -> Canals of Hering (intralobar bile duct) -> interlobular bile ducts -> intrahepatic bile ducts -> left and right hepatic ducts merge to form -> common hepatic duct *exits liver* and joins -> cystic duct (from gall bladder) forming -> common bile duct -> joins with pancreatic duct -> forming ampulla of Vater -> enters duodenum [WP]
Artery that supplies blood to the liver.[TAO]
An endoderm derived structure that produces precursors of digestive enzymes and blood glucose regulating enzymes[GO].
Organ which secretes a fluid containing enzymes that aid in the digestion of food.[AAO]
In the hagfish and lampreys (our most primitive vertebrate species of today), the first sign of 'a new organ' is found as collections of endocrine cells around the area of the bile duct connection with the duodenum. These endocrine organs are composed of 99% beta cells and 1% somatostatin-producing delta cells. Compared to the more primitive protochordates (e.g. amphioxus), this represents a stage where all previously scattered insulin-producing cells of the intestinal tissue have now quantitatively migrated to found a new organ involved in sensing blood glucose rather than gut glucose. Only later in evolution, the beta cells are joined by exocrine tissue and alpha cells (exemplified by the rat-, rabbit- and elephant-fishes). Finally, from sharks and onwards in evolution, we have the islet PP-cell entering to complete the pancreas.[well established][VHOG]
As a secretory organ serving exocrine and endocrine functions, the pancreas is specific to the vertebrates[PMID:16417468] Hagfishes and lampreys are unique in the complete separation of their endocrine pancreas (islet or- gan) and their exocrine pancreas (50). The endocrine and exocrine pancreas are coassociated in crown gnathostomes (50). In Branchiostoma and Ciona, there is no diverticulum as there is in hagfishes, lampreys, and gnathostomes, only dispersed insulin-secreting cells in the walls of the gastrointestinal tract (51, 52)
The mature pancreas of higher vertebrates and mammals comprises two major functional units: the exocrine pancreas, which is responsible for the production of digestive enzymes to be secreted into the gut lumen, and the endocrine pancreas, which has its role in the synthesis of several hormones with key regulatory functions in food uptake and metabolism. The exocrine portion constitutes the majority of the mass of the pancreas, and contains only two different cell types, the secretory acinar cells and the ductular cells. The endocrine portion, which comprises only 1-2% of the total mass, contains five different cell types, which are organized into mixed functional assemblies referred to as the islets of Langerhans
Wide thin-walled blood vessels in the liver. In mammals they have neither veinous or arterial markers.
An intercellular channel that takes up bile from hepatocytes, transporting it to the bile ducts.
Anatomical system that is a multi-element, multi-tissue anatomical cluster that consists of the skeleton and the articular system.
Anatomical system consisting of multiple elements and tissues that provides physical support.[TAO]
Anatomical system that is a multi-element, multi-tissue anatomical cluster that consists of the skeleton and the articular system.[VSAO]
System that provides physical support to the organism.[AAO]
By taking a holistic approach, integration of the evidence from molecular and developmental features of model organisms, the phylogenetic distribution in the 'new animal phylogeny' and the earliest fossilized remains of mineralized animal skeletons suggests independent origins of the skeleton at the phylum level.[debated][VHOG]
Organ consisting of a tissue made up of various elongated cells that are specialized to contract and thus to produce movement and mechanical work[GO].
Portion of tissue composed of contractile fibers.[TAO]
It seems clear that the metazoan ancestor inherited from its unicellular descendants an actin cytoskeleton and motor-proteins of the myosin superfamily. Within metazoans, these two molecules were arranged into effective contractile units, the muscles. The basic trends for muscle evolution are already expressed in the diploblastic taxa.[well established][VHOG]
An epithelial tube or tree of tibes that transports blood away from the heart[modified from AEO definition].
Note that in FMA an artery is a tree, whereas AEO/JB defines it as a tube; FMA includes a separate class for what it calls the trunk. Classification in this ontology may currently (Jan 2012) represent a mix of both schemes, although we are gradually revising in the direction of the AEO scheme.
Part of the circulatory system composed of blood vessels which carry oxygenated blood away from the heart to the rest of the body.[AAO]
The appearance of Chordata and subsequently the vertebrates is accompanied by a rapid structural diversification of this primitive linear heart: looping, unidirectional circulation, an enclosed vasculature, and the conduction system.[well established][VHOG]
Any of the tubular branching vessels that carry blood from the capillaries toward the heart.
TODO - check with MA - vein vs venous blood vessel
Part of the circulatory system composed of blood vessels which carry blood from other organs, tissues, and cells to the heart.[AAO]
Sense organ in vertebrates that is specialized for the detection of sound, and the maintenance of balance. Includes the outer ear and middle ear, which collect and transmit sound waves; and the inner ear, which contains the organs of balance and (except in fish) hearing. Also includes the pinna, the visible part of the outer ear, present in some mammals.
The organ of hearing and of equilibrium. [TFD][VHOG]
Both vertebrate and invertebrate auditory organs are thought to have evolved from primitive mechanosensors, but the nature of the ancestral structure and the evolutionary trajectories followed in distinct animal lineages remain unknown. In particular, we do not know how many types of mechanosensor existed in the protostome-deuterostome ancestor from which insects and vertebrates evolved or whether the PDA had an auditory organ.[well established][VHOG]
A muscular organ in the floor of the mouth.
in MA the tongue is part of the oral region, which in uberon is treated as the oral opening. consider revising oral opening - oral region equivalence.
A mobile mass of muscular tissue that is covered with mucous membrane, occupies much of the cavity of the mouth, forms part of its floor, bears the organ of taste, and assists in chewing and swallowing. [TFD][VHOG]
Muscular organ in the floor of the mouth.[FEED]
The tongue is the movable, muscular organ on the floor of the mouth of most vertebrates, in many other mammals is the principal organ of taste, aids in the prehension of food, in swallowing, and in modifying the voice as in speech[GO][GO:0043586].
Most adult amphibians have a tongue, as do all known reptiles, birds and mammals. Thus it is likely that the tongue appeared with the establishment of tetrapods and this structure seems to be related, to some extant, to the terrestrial lifestyle.[well established][VHOG]
Many species of fish have small folds at the base of their mouths that might informally be called tongues, but they lack a muscular structure like the true tongues found in most tetrapods
The tongue has contributions from all pharyngeal arches which changes with time. The tongue initially begins as swelling rostral to foramen cecum, the median tongue bud.. tongue muscles derive from the somites - http://php.med.unsw.edu.au/embryology/index.php?title=Tongue_Development#Pharyngeal_Arch_Contributions
The liquid component of blood, in which erythrocytes are suspended.
vital aqueous secretion of the liver that is formed by hepatocytes and modified down stream by absorptive and secretory properties of the bile duct epithelium.
aids the process of digestion of lipids in the small intestine
bile salts function to emulsify dietary fats and facilitate their intestinal absorption
major excretory route for potentially harmful exogenous lipophilic substances
many hormones and pheromones are excreted in bile, and contribute to growth and development of the intestine in some species and provide attractants for the weaning of non-human vertebrates
protects the organism from enteric infections by excreting immune globulin A (IgA), inflammatory cytokines, and stimulating the innate immune system in the intestine
In many species, bile is stored in the gallbladder and upon eating is discharged into the duodenum.
A vessel through which blood circulates in the body.
consider adopting the EMAPA superclass 'vascular element', which includes microvasculature (e.g. capillaries), vascular plexus
should not be confused with the anatomic lobes of the liver (caudate lobe, quadrate lobe, left lobe, and right lobe), or any of the functional lobe classification systems.[WP]
Any of the vessels through which blood circulates in the body. [XAO:0001011_][VHOG]
Any of the vessels through which blood circulates in the body.[AAO]
annelids have blood vessels, but this class is not applicable to annelids.
FMA:63183 Blood vessel is categorized as 'general anatomical term'. Suggestion to map to region of vascular tree from Terry H at JAX
Respiration organ that develops as an oupocketing of the esophagus.
Either of two organs which allow gas exchange absorbing oxygen from inhaled air and releasing carbon dioxide with exhaled air.[AAO]
Lungs had already developed as paired ventral pockets from the intestine in the ancestor of Osteognathostomata. (...) In actinopterygian fishes, apart from Cladistia, the ventral intestinal pocket migrates dorsally and becomes the swim-bladder, a mainly hydrostatical organ (reference 1); Comparative transcriptome analyses indicate molecular homology of zebrafish swimbladder and Mammalian lung (reference 2).[well established][VHOG]
respiration organ in all air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located in the chest on either side of the heart. Their principal function is to transport oxygen from the atmosphere into the bloodstream, and to release carbon dioxide from the bloodstream into the atmosphere. This exchange of gases is accomplished in the mosaic of specialized cells that form millions of tiny, exceptionally thin-walled air sacs called alveoli. // Avian lungs do not have alveoli as mammalian lungs do, they have Faveolar lungs. They contain millions of tiny passages known as para-bronchi, connected at both ends by the dorsobronchi
Snakes and limbless lizards typically possess only the right lung as a major respiratory organ; the left lung is greatly reduced, or even absent. Amphisbaenians, however, have the opposite arrangement, with a major left lung, and a reduced or absent right lung [WP]
The organ covering the body that consists of the dermis and epidermis.
consider 'integumentary system' for invertebrates
the organ that functions to filter blood and to store red corpuscles and platelets
An exocrine gland which secretes bile and functions in metabolism of protein and carbohydrate and fat, synthesizes substances involved in the clotting of the blood, synthesizes vitamin A, detoxifies poisonous substances, stores glycogen, and breaks down worn-out erythrocytes.
Organ which secretes bile and participates in formation of certain blood proteins.[AAO]
All vertebrates possess a liver (reference 1); Later in craniate evolution, an anterior gill arch was transformed into jaws, and many new types of feeding subsequently evolved.(...) A liver evolved that, among its many functions, stores considerable energy as glycogen or lipid (reference 2).[well established][VHOG]
An organ sometimes referred to as a liver is found associated with the digestive tract of the primitive chordate Amphioxus. However, this is an enzyme secreting gland, not a metabolic organ, and it is unclear how truly homologous it is to the vertebrate liver. The zebrafish liver differs from the mammalian liver in that the hepatocytes are not clearly organized in cords or lobules and the typical portal triads are not apparent. In addition, the zebrafish liver does not have Kuppfer cells. Furthermore, a clear distinction can be made between the male and female liver in the adult zebrafish. The female hepatocytes are very basophilic (Figure 15c) as a result of the production of vitellogenin (Van der Ven et al. 2003).
The liver is found in all vertebrates, and is typically the largest visceral organ. Its form varies considerably in different species, and is largely determined by the shape and arrangement of the surrounding organs. Nonetheless, in most species it is divided into right and left lobes; exceptions to this general rule include snakes, where the shape of the body necessitates a simple cigar-like form. The internal structure of the liver is broadly similar in all vertebrates.
secretes bile and functions in metabolism of protein and carbohydrate and fat, synthesizes substances involved in the clotting of the blood, synthesizes vitamin A, detoxifies poisonous substances, stores glycogen, and breaks down worn-out erythrocytes[GO].
Subdivision of digestive tract that connects the stomach to the large intestine and is where much of the digestion and absorption of food takes place (with the exception of ruminants). The mammalian small intestine is long and coiled and can be differentiated histologically into: duodenum, jejunem, ileum[WP,cjm,Kardong].
The terminal region of the mid intestine is comprised of specialized enterocytes that appear to play a role in mucosal immunity. Wallace et al, 2005.[TAO]
Intestinal surface area also is increased in amphibians and reptiles by internal folds and occasionally by a few villi. The intestine can be divided into a small intestine and a slightly wider large intestine.[well established][VHOG]
An organ that aids digestion and stores bile produced by the liver[WP].
Membranous muscular sac in which the bile from the liver remains stored until it is required. [Dorian_AF, Elsevier's_encyclopaedic_dictionary_of_medicine, Part_B:_Anatomy_(1988)_Amsterdam_etc.:_Elsevier][VHOG]
Organ attached to the liver which stores bile and empties into the duodenum via the bile duct as needed for digestion.[AAO]
The presence of a gallbladder appears to be a primitive trait. It is found in most fish and all adult reptiles and amphibians and has been well conserved in mammals, for the most part.[well established][VHOG]
Rats do not have a gallbladder, but produce bile. The bile flows directly from the liver through the (hepatic) bile duct into the small intestine (Hebel and Stromberg, 1988)
A paired organ of the urinary tract which has the production of urine as its primary function.
One of either of a pair of structures lying on either side of the dorsal aorta in which fluid balance is regulated and waste is excreted out in the form of urine.[AAO]
Lung which consists of the right upper lobe, middle lobe and right lower lobe.[FMA]
Lungs had already developed as paired ventral pockets from the intestine in the ancestor of Osteognathostomata.[well established][VHOG]
Lung which consists of the left upper lobe and left lower lobe.[FMA]
Anatomical cluster consisting of the hematopoietic system and the lymphoid system, or its analogs.
Anatomical system that consists of the muscular and skeletal systems.
Anatomical system that provides locomotion and physical support to the organism.[AAO]
There are more than 50,000 extant vertebrate species, representing over 500 million years of evolution. During that time, the vertebrate musculoskeletal systems have adapted to aquatic, terrestrial, fossorial, and arboreal lifestyles, while simultaneously retaining functionally integrated axial and appendicular skeletal systems.[well established][VHOG]
Part of the central nervous system located in the vertebral canal continuous with and caudal to the brain; demarcated from brain by plane of foramen magnum. It is composed of an inner core of gray matter in which nerve cells predominate, and an outer layer of white matter in which myelinated nerve fibers predominate, and surrounds the central canal. (CUMBO)
TODO - add superclass to unify with VNC?
Part of the central nervous system which descends from the hindbrain within the vertebral column.[AAO]
An organ that houses olfactory neurons and is responsible for the sense of smell. Examples include the vertebrate nose and the Drosophila dorsal organ.
An olfactory organ overlaps with the olfactory system, because some parts of the nose (e.g. nasal skeleton) are parts of the skeletal system, which is spatially disjoint
Organ system subdivision that consists of the organs and ducts that are involved in the production and transportation of bile. In most species this is the gallbladder and the bile ducts (biliary tree).
Anatomical system that consists of the glands and parts of glands that produce exocrine secretions and help to integrate and control bodily metabolic activity. Exocrine glands are glands that secrete their products (hormones) into ducts (duct glands). They are the counterparts to endocrine glands, which secrete their products (hormones) directly into the bloodstream (ductless glands) or release hormones (paracrines) that affect only target cells nearby the release site. [Wikipedia].
A gland that secretes products (excluding hormones and other chemical messengers) into ducts (duct glands) which lead directly into the external environment. Typical exocrine glands include sweat glands, salivary glands, mammary glands, stomach, liver, pancreas
Endocrine glands are glands of the endocrine system that secrete their products directly into the circulatory system rather than through a duct.
the soft tissue that fills the cavities of bones
Tissue with cells that deposit non-polarized extracellular matrix including connective tissue fibers and ground substance.
One of the four types of tissue in traditional classifications. It is largely a category of exclusion rather than one with a precise definition, but there are certain characteristics shared by all or most tissues in this category, such as involvement in structure and support, derived from mesoderm, and characterized largely by the traits of non-living tissue.[AAO]
Portion of tissue that consists of mesodermally derived cells and intercellular matrix comprised of protein fibers and carbohydrates, which supports, ensheathes and binds together other tissues.[TAO]
Tissue with cells that deposit non-polarized extracellular matrix including connective tissue fibers and ground substance.[VSAO]
Muscle tissue is a contractile tissue made up of actin and myosin fibers[GO].
One of the four types of tissue in traditional classifications. Tissue that contains cells with contractile filaments that move past each other and change the size of the cell. Muscle tissue also is separated into three distinct categories.[AAO]
Vertebrate muscle is categorized into three major muscle types defined by their structural and functional properties: skeletal, cardiac and smooth. In Dmel the counterparts are somatic, heart/cardiac and visceral. Here we take a cell type based approach.
Anatomical system that is involved in the production of hematopoietic cells.
Anatomical system that consists of the blood and blood forming tissues.[AAO]
Zebrafish developmental hematopoiesis shows close correspondence to the development of the mammalian hematopoietic system and is regulated by conserved molecular pathways.[well established][VHOG]
In humans this is primarily the bone marrow, spleen, tonsils, and lymph nodes
Any of the ducts that form the biliary tree, carrying bile from the liver to the small intestine.
Anatomical system that protects the body from foreign substances, cells, and tissues by producing the immune response and that includes especially the thymus, spleen, lymphoid tissue, lymphocytes including the B cells and T cells, and antibodies.
The antibody-based immune system defined by the presence of the major histocompatibility complex (MHC), T cell receptor (TCR), B cell receptor (BCR) or recombination activating genes (RAGs) is known beginning from jawed fishes.[well established][VHOG]
Connected anatomical system that forms a barrier between an animal and its environment. In vertebrates, the integumental system consists of the epidermis, dermis plus associated glands and adnexa such as hair and scales. In invertebrates, the integumental system may include cuticle.
(...) the integument of many tetrapods is reinforced by a morphologically and structurally diverse assemblage of skeletal elements. These elements are widely understood to be derivatives of the once all-encompassing dermal skeleton of stem-gnathostomes (...).[well established][VHOG]
The part of the digestive system that contains the liver and the biliary system
System responsible for the production and movement of bile[ZFIN:curator].
The hepaticobiliary system is responsible for metabolic and catabolic processing of small molecules absorbed from the blood or gut, hormones and serum proteins, detoxification, storage of glycogen, triglycerides, metals and lipid soluble vitamins and excretion of bile. Included are the synthesis of albumin, blood coagulation factors, complement, and specific binding proteins. The parts are: liver, bile duct, gall bladder and hepatic duct [GO:0061008]
Skeletal tissue with a collagen-rich extracellular matrix vascularized, mineralized with hydroxyapatite and typically including osteocytes located in lacunae that communicate with one another by cell processes (in canaliculi). Bone is deposited by osteoblasts.
see https://github.com/obophenotype/uberon/issues/27
Skeletal tissue with a collagen-rich extracellular matrix vascularized, mineralized with hydroxyapatite and typically including osteocytes located in lacunae that communicate with one another by cell processes (in canaliculi). Bone is deposited by osteoblasts.[VSAO]
An organ that functions as a secretory or excretory organ
female organism reproductive system organ
reproductive structure of female organism
reproductive system organ of female organism
A blood vessel that is part of a retina.
A blood vessel that is part of the arterial system. Includes artery, arteriole and aorta.
only in MA - supertype of artery, arteriole, aorta.
small blood vessel similar to a capillary but with a fenestrated endothelium. Sinusoids are found in the liver, lymphoid tissue, endocrine organs, and hematopoietic organs such as the bone marrow and the spleen. Sinusoids found within terminal villi of the placenta are not comparable to these; they possess a continuous endothelium and complete basal lamina[WP].
A blood vessel that carries blood from the capillaries toward the heart
A duct that is part of a digestive system [Automatically generated definition].
Any tube, opening or passage that connects two distinct anatomical spaces.
Anatomical system that has as its parts the organs concerned with the production and excretion of urine and those concerned with reproduction.
Anatomical system that has as its parts the organs concerned with the production and excretion of urine and those concerned with reproduction.[AAO]
Kidneys and gonads (of vertebrates) develop from adjacent tissues, and after the excretory or urinary ducts have developed, the reproductive system usually taps into them or their derivatives.[well established][VHOG]
Anatomical cluster that consists of all the skeletal elements (eg., bone, cartilage, and teeth) of the body.
Anatomical cluster that consists of all the skeletal elements (eg., bone, cartilage, and teeth) of the body.[VSAO]
Anatomical system that has as its parts the heart and blood vessels.
we treat cardiovascular as part of circulatory system, with the latter including other kinds of circulation, including lymph.
The vessels of the cardiovascular system are as varied as the diverse organs they supply. However, these variations are based on modifications of a fundamental plan of organization common to vertebrates.[well established][VHOG]
The part of the arterial system which carries oxygenated blood away from the heart to the body, and returns deoxygenated blood back to the heart.
The part of the cardiovascular system consisting of all arteries.
The part of the cardiovascular system consisting of all venous vessels. In vertebrates with a double circulation, this can be divided into systemic and pulmonary portions.
A specialized form of connective tissue in which the extracellular matrix is firm, providing the tissue with resilience, and/or mineralized and that functions in mechanical and structural support.[VSAO]
Four classes of mineralized tissues are found in vertebrates: bone, cartilage, dentine, and enamel. We think of cartilage and bone as skeletal tissues and of enamel and dentine as dental tissues, but enamel and dentine arose evolutionarily together with bone as skeletal tissues in the dermal skeleton (exoskeleton) of early vertebrates. Scales and teeth of sharks are examples of dermal skeletal elements that are still composed of the three ancient components-enamel, dentine, and bone. Cartilage, on the other hand, provided the basis for the second vertebrate skeletal system, the endoskeleton (Smith and Hall, 1990; Hall, 1998a,b). some invertebrate skeletal tissues have surprisingly bone-like features. Examples include chondrocytes interconnected by cell processes in cephalopod cartilages (Cole and Hall, 2004a,b), and the calcium phosphate layer in the shells of brachiopods (Rodland et al., 2003). However, neither bone nor mineralized cartilage have been found in invertebrates. Editors notes: TODO - develops_from
Anatomical system that consists of all the joints of the body.
Liquid components of living organisms. includes fluids that are excreted or secreted from the body as well as body water that normally is not.
Vein that is central to a lobule in the liver.
Anatomical system that consists of all blood and lymph vessels.
The cardiovascular and lymphatic systems, collectively[ncithesaurus:Vascular_System].
An anatomical structure that has more than one cell as a part.
An anatomical space which is the lumen of some anatomical conduit and connects two or more spaces together [FMA,modified].
Any of the organs or elements that are part of the digestive system. Examples: tongue, esophagus, spleen, crop, lunge feeding organ, tooth elements.
A muscle organ that consists of skeletal muscle tissue ensheathed in epimysium, that develops from myotome and that is innervated by some somatic motor neuron. Skeletal muscles are typically attached (via a tendon) to a bone but there are exceptions (e.g. intrinsic tongue muscles).
The hepatic artery proper (also proper hepatic artery), arises from the common hepatic artery and runs alongside the portal vein and the common bile duct to form the portal triad. The hepatic artery proper gives off a small supraduodenal artery to the duodenal bulb. Then the right gastric artery comes off and runs to the left along the lesser curvature of the stomach to meet the left gastric artery, which is a branch of the celiac trunk. It subsequently gives off the cystic artery, which feeds the gallbladder, before bifurcating into the right and left hepatic arteries. Of note, the right and left hepatic arteries may demonstrate variant anatomy. A replaced right hepatic artery may arise from the superior mesenteric artery (SMA) and a replaced left hepatic artery may arise from the left gastric artery.
A hepatic artery that is part of a left lobe of liver.
ramus sinister (arteria hepatica propria)
A hepatic artery that is part of a right lobe of liver.
A collection of anatomical structures that are alike in terms of their morphology or developmental origin.
resolve if this should be a subclass of disconnected anatomical group. Some collections (e.g. the skeleton or skull) are arguably connected
Typically small, circular, intronless, and maternally inherited, mitochondrial DNA (mtDNA) is the multicopy deoxyribonucleic acid genome of mitochondria, intracellular organelles responsible for vital respiratory chain and oxidative phosphorylation reactions in higher eukaryotes. Replicated and transcribed by a separate enzymatic machinery from that of nuclear DNA, mtDNA encodes only a subset of mitochondrial functions. (by EFO)
To say that each spatiotemporal region s temporally_projects_onto some temporal region t is to say that t is the temporal extension of s. (axiom label in BFO2 Reference: [080-003])
To say that spatiotemporal region s spatially_projects_onto spatial region r at t is to say that r is the spatial extent of s at t. (axiom label in BFO2 Reference: [081-003])