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 Szabó

    Research output: Contribution to journalArticlepeer-review

    93 Scopus citations

    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

    Keywords

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

    ASJC Scopus subject areas

    • Neuroscience(all)

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