Poly(ADP-ribose) polymerase-1 mediated caspase-independent cell death after ischemia/reperfusion

S.J. van Wijk, G.J. Hageman*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


In ischemia/reperfusion (I/R) injury increased intracellular Ca(2+) and production of reactive oxygen species (ROS) may cause cell death by intrinsic apoptotic pathways or by necrosis. In this review, an alternative intrinsic cell death pathway, mediated by poly(ADP-ribose) polymerase-1 (PARP-1) and apoptosis-inducing factor (AIF), is described. ROS-induced DNA strand breaks lead to overactivation of the nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1; EC, causing excessive use of energetic substrates such as NAD(+) and ATP, inducing cell death either by apoptosis or by necrosis. Recently, it was demonstrated that activation of PARP-1 induces translocation of apoptosis-inducing factor from the mitochondria to the nucleus, causing DNA condensation and fragmentation, and subsequent cell death. This pathway seems to be triggered by depletion of NAD(+) and appears to be caspase independent. Several lines of evidence suggest that this pathway plays a role in I/R injury, although some studies indicate that mitochondrial dysfunction may also trigger AIF translocation and cell death. At present, the exact mechanisms linking PARP-1 and AIF in the induction of the ROS-induced cell death are still unclear. Therefore, it appears that further investigations will yield valuable information on underlying mechanisms and potential interventions to reduce caspase-independent cell death during ischemia-reperfusion.
Original languageEnglish
Pages (from-to)81-90
JournalFree Radical Biology and Medicine
Issue number1
Publication statusPublished - 1 Jan 2005

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