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Event: 66
Key Event Title
A descriptive phrase which defines a discrete biological change that can be measured.
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Activation, ChREBP
Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki.
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Activation, ChREBP
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A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided.
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ChREBP is an LXR target that independently enhances the up-regulation of select lipogenic genes. The up-regulation of the ChREBP target gene is through liver-type pyruvate kinase (L-PK). Therefore, activation of LXR not only increases ChREBP mRNA via enhanced transcription but also modulates its activity [1]. In the liver, ChREBP mediates activation of several regulatory enzymes of glycolysis and lipogenesis including L-PK, acetyl CoA carboxylase (ACC), and fatty acid synthase (FAS). However, according to the study of Denechaud increase in the glucose flux in the cell is a prerequisite for ChREBP activation from T0901317 in mice [2].
In the context of the EMOD/M2AOP prototyping, there are 2 components to the How it is Measured or Detected field, a structured component for adding Assay information and a free text component for unstructured descriptive information.In the free text field, include a description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements. These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols.
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Observed meausures are instances of assay results that support this Key Event
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| ID | Experimental Effect | Biological Object | Biological Process | Method of Measurement | Notes | Evidence Source ID | Citation (first author, year) |
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Observed meausures are instances of assay results that support this Key Event
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| ID | Stressor | Sample (short_name) | Assay | Effect |
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The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling). The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor). Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description. To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons. If a desired term does not exist, a new term request may be made via Term Requests. Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add. Further information on Event Components and Biological Context may be viewed on the attached pdf.
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| Process | Object | Action |
|---|---|---|
| signaling | carbohydrate-responsive element-binding protein | increased |
Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE.
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| Level of Biological Organization |
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| Molecular |
Cell term
The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place. For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable. For individual/population events, the organ context is not applicable. Further information on Event Components and Biological Context may be viewed on the attached pdf.
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| Cell term |
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| hepatocyte |
Organ term
The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place. For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable. For individual/population events, the organ context is not applicable. Further information on Event Components and Biological Context may be viewed on the attached pdf.
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AOPs Including This Key Event
All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP.
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| AOP Name | Role of event in AOP | Point of Contact | Author Status | OECD Status |
|---|---|---|---|---|
| LXR Activation to Liver Steatosis | KeyEvent | Agnes Aggy (send email) | Not under active development | |
| NR1I3 suppression to steatosis | KeyEvent | Allie Always (send email) | Under Development: Contributions and Comments Welcome |
Taxonomic Applicability
Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE.
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Life Stages
An indication of the the relevant life stage(s) for this KE.
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Sex Applicability
An indication of the the relevant sex for this KE.
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A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).
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List of the literature that was cited for this KE description.
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