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Event: 1967

Key Event Title

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

Pyroptosis

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
Pyroptosis
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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
SARS-CoV2 to pyroptosis AdverseOutcome Hasmik Yepiskoposyan (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

Pyroptosis is an inflammatory form of programmed cell death. Pore-forming protein gasdermins (GSDM) are crucial factors for pyroptosis execution whereby GSDMD and GSDME are most deeply studied [1]. Pyroptosis is initiated through inflammasome activation resulting to activation of caspase-1 (CASP1). Active CASP1 cleaves GSDMD, and also cleaves and thus activates pro-inflammatory cytokines interleukin-1B (IL1B) and IL18 [2]. N-terminal cleaved domain of GSDMD forms pores in the plasma membrane leading to cell swelling and pyroptotic cell death [3, 4]. IL1B and IL18 are released through the pores contributing to inflammatory and pyroptotic processes.

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

A common way to measure pyroptosis is through enzymatic assays for detection of lactate hydrogenase (LDH). LDH is released when plasma membrane is damaged and is a common measure of cytotoxicity. LDH release assays using commercially available kit and a quick, cost-effective method adapted from Decker et al [8] are described by Rayamajhi and colleagues [9]. Den Hartigh and Fink also describe LDH release assay as well as fluorescent microscopy method for visualization of loss of membrane integrity during pyroptosis [10]. Pyroptosis initiation can be inferred from CASP1 activation hence the CASP1 Fluorescein Assay (FLICA) is also used by researchers as detection method [11, 12]. Furthermore, Hoechst 33342 (chromatin condensation detection) and propidium iodide (probe for membrane damage) double staining can be used for pyroptotic cell detection although this method also detects other cell death types (e.g. apoptotis) [11, 13].

Domain of Applicability

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

Regulatory Significance of the Adverse Outcome

An AO is a specialised KE that represents the end (an adverse outcome of regulatory significance) of an AOP. More help

References

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

1. Yu, P., et al., Pyroptosis: mechanisms and diseases. Signal Transduct Target Ther, 2021. 6(1): p. 128. 

2. Kelley, N., et al., The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation. Int J Mol Sci, 2019. 20(13). 

3. He, W.T., et al., Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion. Cell Res, 2015. 25(12): p. 1285-98. 

4. Sborgi, L., et al., GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death. Embo j, 2016. 35(16): p. 1766-78. 

5. Farag, N.S., et al., Viroporins and inflammasomes: A key to understand virus-induced inflammation. Int J Biochem Cell Biol, 2020. 122: p. 105738. 

6. Shah, A., Novel Coronavirus-Induced NLRP3 Inflammasome Activation: A Potential Drug Target in the Treatment of COVID-19. Front Immunol, 2020. 11: p. 1021. 

7. Xu, H., et al., SARS-CoV-2 viroporin triggers the NLRP3 inflammatory pathway. bioRxiv, 2020: p. 2020.10.27.357731. 

8. Decker, T. and M.L. Lohmann-Matthes, A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity. J Immunol Methods, 1988. 115(1): p. 61-9. 

9. Rayamajhi, M., Y. Zhang, and E.A. Miao, Detection of pyroptosis by measuring released lactate dehydrogenase activity. Methods Mol Biol, 2013. 1040: p. 85-90. 

10. den Hartigh, A.B. and S.L. Fink, Pyroptosis Induction and Detection. Curr Protoc Immunol, 2018. 122(1): p. e52. 

11. Chen, A., et al., Rosuvastatin protects against coronary microembolization-induced cardiac injury via inhibiting NLRP3 inflammasome activation. Cell Death Dis, 2021. 12(1): p. 78. 

12. Wang, Y., et al., Caspase-1-Dependent Pyroptosis of Peripheral Blood Mononuclear Cells Is Associated with the Severity and Mortality of Septic Patients. Biomed Res Int, 2020. 2020: p. 9152140. 

13. Chen, A., et al., Liraglutide attenuates NLRP3 inflammasome-dependent pyroptosis via regulating SIRT1/NOX4/ROS pathway in H9c2 cells. Biochem Biophys Res Commun, 2018. 499(2): p. 267-272.