API

Event: 1575

Key Event Title

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Activation, Caspase 8 pathway

Short name

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Activation, Caspase 8 pathway

Biological Context

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Level of Biological Organization
Molecular

Cell term

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Organ term

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Key Event Components

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Process Object Action

Key Event Overview


AOPs Including This Key Event

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AOP Name Role of event in AOP
IKK complex inhibition leading to liver injury KeyEvent

Stressors

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Taxonomic Applicability

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Life Stages

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Sex Applicability

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Key Event Description

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In the caspase 8 pathway, the TRADD adaptor protein recruits FADD after TNFa stimulus and forms a complex together with pro-caspase 8. Caspase 8 will be activated and can directly activate caspase-3 which leads to apoptosis (Melino & Vaux 2010). Furthermore, Caspase 8 can also splice Bid to tBid which promotes disruption of the membrane of mitochondria. Cytochrome C will be released and activate Caspase 9 and Apaf1, which in turn stimulate caspase 8, causing apoptosis (Frederiksson 2012).(Cullen & Martin 2009)


How It Is Measured or Detected

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WesternBlot (pro) caspase 8 (Fotin-Mleczek et al. 2002)(Schattenberg et al. 2011)

Caspase 8 specific fluorogenic substrates(Schattenberg et al. 2011)


Domain of Applicability

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References

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Melino, G. & Vaux, D., 2010. Cell Death G. Melino & D. Vaux, eds.,

Frederiksson, L., 2012. TNFalpha-signaling in drug induced liver injury. University of Leiden.

Cullen, S.P. & Martin, S.J., 2009. Caspase activation pathways: Some recent progress. Cell Death and Differentiation, 16(7), pp.935–938. Available at: http://dx.doi.org/10.1038/cdd.2009.59.

Fotin-Mleczek, M. et al., 2002. Apoptotic crosstalk of TNF receptors: TNF-R2-induces depletion of TRAF2 and IAP proteins and accelerates TNF-R1-dependent activation of caspase-8. Journal of cell science, 115(Pt 13), pp.2757–2770.

Schattenberg, J.M. et al., 2011. Ablation of c-FLIP in hepatocytes enhances death-receptor mediated apoptosis and toxic liver injury in vivo. Journal of Hepatology, 55(6), pp.1272–1280. Available at: http://dx.doi.org/10.1016/j.jhep.2011.03.008.