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Event: 1513
Key Event Title
General Apoptosis
Short name
Biological Context
Level of Biological Organization |
---|
Cellular |
Cell term
Organ term
Key Event Components
Process | Object | Action |
---|---|---|
increased apoptosis | increased |
Key Event Overview
AOPs Including This Key Event
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 | Jelle Broeders (send email) | Under development: Not open for comment. Do not cite | |
ROS formation leads to cancer via inflammation pathway | KeyEvent | John Frisch (send email) | Under development: Not open for comment. Do not cite | |
ROS formation leads to cancer via PPAR pathway | KeyEvent | John Frisch (send email) | Under development: Not open for comment. Do not cite |
Taxonomic Applicability
Life Stages
Life stage | Evidence |
---|---|
All life stages | High |
Sex Applicability
Term | Evidence |
---|---|
Unspecific | High |
Key Event Description
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 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 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
There are several possibilities to measure and detect apoptosis, some common techniques are:
- The detection of Lactate dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) substances which are released from cells which undergo apoptosis.
- 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.
- Another technique is the detection of cleaved caspase-3, which could be done with 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 in addition to western blot assay.
Domain of Applicability
Taxonomic: appears to be present broadly among multicellular organisms.
References
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).