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Event: 1509

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Protein Adduct Formation

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. More help
Protein Adduct Formation
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
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. More help

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. More help
Organ term
brain

Key Event Components

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. More help

Key Event Overview

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. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
CYP2E1 activation and formation of protein adducts leading to neurodegeneration MolecularInitiatingEvent Brendan Ferreri-Hanberry (send email) Under development: Not open for comment. Do not cite

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. More help

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Sex Applicability

An indication of the the relevant sex for this KE. More help

Key Event Description

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. More help

Reactive chemicals or metabolites can interact with proteins present in any cell type which occur at the molecular level. The electrophilic chemicals react with the nucleophilic parts of proteins, forming a covalent bond. When proteins are in their original shape they can function properly, when this is not the case the protein loses its function. These are unspecific proteins which are altered in shape due to the covalent binding of chemicals.

How It Is Measured or Detected

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. More help

The determination of protein adducts can be done, but since some chemicals induce protein adducts at low abundance it is hard to measure. A new technique is developed to overcome the problem of the low abundance. A drug is labelled with a biotin affinity tag, which than can react with proteins and bind covalently. After incubation with several proteins the drugs attached to the proteins are separated from the rest of the free proteins with the use of the tag. Next the proteins which are altered by the drug can be identified with proteomics. A LC/MS/MS technique is used. A problem which can occur, is that the use of a tag can influence the binding profile of the drug. Another possibility is the use of 2D gel-electrophoresis and tandem mass spectrometry based proteomics. Proteins are purified from cells after incubation with a drug. With 2D gel-electrophoresis the proteins are separated, afterwards the spots of interest are identified with tandem mass spectrometry.

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

References

List of the literature that was cited for this KE description. More help

LoPachin, R. M. & DeCaprio, A. P. Protein adduct formation as a molecular mechanism in neurotoxicity. Toxicological Sciences 86, 214–225 (2005)

Gan, J., Zhang, H. & Humphreys, W. G. Drug-Protein Adducts: Chemistry, Mechanisms of Toxicity, and Methods of Characterization. Chemical Research in Toxicology 29, 2040–2057 (2016)