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Event: 1513

Key Event Title

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

General Apoptosis

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
General Apoptosis
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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
Cellular

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

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 KeyEvent 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

Apoptosis is the programmed cell death in general. This process is well regulated with a sequence of events before cell fragmentation occurs. Changes in the nucleus of a neuron cell are the first step in apoptosis. Before that, other factors such as stress, inflammation, cell damage can induce expression or activation of signal proteins which will activate the pathway for apoptosis. Examples of proteins which are involved in apoptosis are the proteins p53, Bcl-2, JNK, and several caspases. When the first step is taken in the apoptosis process the neuron cell will end in membrane-bounded apoptotic bodies. These bodies are cleared by macrophages or other cells where the degradation process starts within heteorphagosomes.

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

There are several possibilities to measure and detect apoptosis, some examples are the detection of LDH and MTT substances which are released from cells which commit suicide. An older but effective technique it the annexin V – affinity assay. The principle of this assay is the high affinity binding between annexin V and phosphatidylserine. In a vital cell there is a membrane lipid asymmetry where phosphatidylserine molecules are facing the cytosol. During apoptosis the membrane lipid asymmetry is lost, and the phosphatidylserine molecules are expressed in the outer membrane. When annexin-V is present in combination with Ca2+ it binds with high affinity to phosphatidylserine. With a hapten label at the annexin-V this process can be detected.

Other techniques are the detection of cleaved caspase-3, which could be done with a western blot or enzyme-linked immunosorbent assays. Cytochrome c is also a protein which is released in an early stage of apoptosis. Detection of cytochrome c can be done with metal nanoclusters which have a fluorescent probe.

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

Shtilbans, V., Wu, M. & Burstein, D. E. Evaluation of apoptosis in cytologic specimens. Diagnostic Cytopathology 38, 685–697 (2010).

Wu, J., Sun, J. & Xue, Y. Involvement of JNK and P53 activation in G2/M cell cycle arrest and apoptosis induced by titanium dioxide nanoparticles in neuron cells. Toxicol. Lett. 199, 269–276 (2010).

Redza-Dutordoir, M. & Averill-Bates, D. A. Activation of apoptosis signalling pathways by reactive oxygen species. Biochim. Biophys. Acta - Mol. Cell Res. 1863, 2977–2992 (2016).

Lossi, L., Castagna, C. & Merighi, A. Neuronal cell death: An overview of its different forms in central and peripheral neurons. in Neuronal Cell Death: Methods and Protocols 1–18 (2014). doi:10.1007/978-1-4939-2152-2_1

Van Engeland, M., Nieland, L. J. W., Ramaekers, F. C. S., Schutte, B. & Reutelingsperger, C. P. M. Annexin V-affinity assay: A review on an apoptosis detection system based on phosphatidylserine exposure. Cytometry 31, 1–9 (1998).

Shamsipur, M., Molaabasi, F., Hosseinkhani, S. & Rahmati, F. Detection of Early Stage Apoptotic Cells Based on Label-Free Cytochrome c Assay Using Bioconjugated Metal Nanoclusters as Fluorescent Probes. Anal. Chem. 88, 2188–2197 (2016).