Endonuclease G does not play an obligatory role in poly(ADP-ribose) polymerase-dependent cell death after transient focal cerebral ischemia

Zhenfeng Xu, Jian Zhang, Karen K. David, Zeng Jin Yang, Xiaoling Li, Ted M. Dawson, Valina L. Dawson, Raymond C. Koehler

Research output: Contribution to journalArticle

Abstract

Activation of poly-(ADP-ribose) polymerase (PARP) and subsequent translocation of apoptosis-inducing factor contribute to caspase-independent neuronal injury from N-methyl-D-aspartate, oxygen-glucose deprivation, and ischemic stroke. Some studies have implicated endonuclease G in the DNA fragmentation associated with caspase-independent cell death. Here, we compared wild-type and endonuclease G null mice to investigate whether endonuclease G plays a role in the PARP-dependent injury that results from transient focal cerebral ischemia. Latex casts did not reveal differences in the cerebral arterial distribution territory or posterior communicating arterial diameter, and the decrease in laser-Doppler flux during middle cerebral artery occlusion was similar in wild-type and endonuclease G null mice. After 90 min of occlusion and 1 day of reperfusion, similar degrees of nuclear translocation of apoptosis-inducing factor and DNA degradation were evident in male wild-type and null mice. At 3 days of reperfusion, infarct volume and neurological deficit scores were not different between male wild-type and endonuclease G null mice or between female wild-type and endonuclease G null mice. These data demonstrate that endonuclease G is not required for the pathogenesis of transient focal ischemia in either male or female mice. Treatment with a PARP inhibitor decreased infarct volume and deficit scores equivalently in male wild-type and endonuclease G null mice, indicating that the injury in endonuclease G null mice remains dependent on PARP. Thus endonuclease G is not obligatory for executing PARP-dependent injury during ischemic stroke.

Original languageEnglish (US)
Pages (from-to)R215-R221
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume299
Issue number1
DOIs
StatePublished - Jul 2010

Keywords

  • Apoptosis
  • DR2313
  • Middle cerebral artery
  • Mouse

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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