Role of peroxynitrite and neuronal nitric oxide synthase in the activation of poly(ADP-ribose) synthetase in a murine model of cerebral ischemia-reperfusion

Matthias Endres, Gwen Scott, Shobu Namura, Andrew L. Salzman, Paul L. Huang, Michael A. Moskowitz, Csaba Szabo

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Poly(ADP-ribose) synthetase (PARS) activation, a downstream event of nitric oxide (NO) neurotoxicity has been implicated in cerebral reperfusion injury. The aim of our study was to identify the trigger of PARS activation during stroke. Formation of poly(ADP-ribose) profoundly increased in the early phase of reperfusion. Poly(ADP-ribose) formation was attenuated in mice deficient for neuronal NO synthase (nNOS). We next tested in glioma cells whether NO, or peroxynitrite (a cytotoxic oxidant formed from NO and superoxide) is the actual trigger of PARS activation. Peroxynitrite, but not various NO donors, activated PARS and suppressed cellular viability in a PARS-dependent fashion. Thus, nNOS is responsible for PARS activation in stroke. PARS activation, however, is not a direct result of NO production, but it occurs via peroxynitrite formation.

Original languageEnglish (US)
Pages (from-to)41-44
Number of pages4
JournalNeuroscience Letters
Volume248
Issue number1
DOIs
StatePublished - May 22 1998
Externally publishedYes

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Poly Adenosine Diphosphate Ribose
Nitric Oxide Synthase Type I
Peroxynitrous Acid
Ligases
Brain Ischemia
Reperfusion
Nitric Oxide
Stroke
Nitric Oxide Donors
Reperfusion Injury
Oxidants
Nitric Oxide Synthase
Glioma
Superoxides

Keywords

  • Cerebral ischemia
  • Neuronal nitric oxide synthase
  • Peroxynitrite
  • Poly(ADP-ribose) synthetase
  • Reperfusion

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Role of peroxynitrite and neuronal nitric oxide synthase in the activation of poly(ADP-ribose) synthetase in a murine model of cerebral ischemia-reperfusion. / Endres, Matthias; Scott, Gwen; Namura, Shobu; Salzman, Andrew L.; Huang, Paul L.; Moskowitz, Michael A.; Szabo, Csaba.

In: Neuroscience Letters, Vol. 248, No. 1, 22.05.1998, p. 41-44.

Research output: Contribution to journalArticle

Endres, Matthias ; Scott, Gwen ; Namura, Shobu ; Salzman, Andrew L. ; Huang, Paul L. ; Moskowitz, Michael A. ; Szabo, Csaba. / Role of peroxynitrite and neuronal nitric oxide synthase in the activation of poly(ADP-ribose) synthetase in a murine model of cerebral ischemia-reperfusion. In: Neuroscience Letters. 1998 ; Vol. 248, No. 1. pp. 41-44.
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