Contributions of poly(ADP-ribose) polymerase-1 and -2 to nuclear translocation of apoptosis-inducing factor and injury from focal cerebral ischemia

Xiaoling Li, Judith A. Klaus, Jian Zhang, Zhenfeng Xu, Kathleen K. Kibler, Shaida A. Andrabi, Karthik Rao, Zeng Jin Yang, Ted M. Dawson, Valina L. Dawson, Raymond C. Koehler

Research output: Contribution to journalArticle


Excessive oxidative damage to DNA leads to activation of poly(ADP-ribose) polymerase-1 (PARP-1), accumulation of PAR polymers, translocation of apoptosis-inducing factor (AIF) from mitochondria to the nucleus, and cell death. In this study, we compared the effect of gene deletion of PARP-1 and PARP-2, enzymes activated by DNA oxidative damage, in male mice subjected to 2 h of focal cerebral ischemia. Infarct volume at 3 days of reperfusion was markedly decreased to a similar extent in PARP-1- and PARP-2-null mice. The ischemia-induced increase in nuclear AIF accumulation was largely suppressed in both knockout genotypes. The transient increase in PAR during early reperfusion was nearly blocked in PARP-1-null mice, but only moderately decreased at 1-h reperfusion in PARP-2-null mice. Differences in the tissue volume at risk, as assessed by arterial casts and autoradiographic analysis of regional blood flow, did not fully account for the large reductions in AIF translocation and infarct volume in both PARP null mice. Cell death was attenuated in PARP-2-null neurons exposed to a submaximal concentration of 100 μM NMDA for 5 min, but not in those exposed to a near-maximal toxic concentration of 500 μM NMDA. We conclude that PARP-2 contributes substantially to nuclear translocation of AIF and infarct size after transient focal cerebral ischemia in male mice, but that protection is disproportionate to the attenuation of overall PARP activity.

Original languageEnglish (US)
Pages (from-to)1012-1022
Number of pages11
JournalJournal of Neurochemistry
Issue number4
StatePublished - May 1 2010



  • Cerebral blood flow
  • Iodoantipyrine
  • Middle cerebral artery
  • NMDA
  • Poly(ADP-ribose) polymers
  • Stroke

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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