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

被引：102
作者：
Endres, M
Scott, G
Namura, S
Salzman, AL
Huang, PL
Moskowitz, MA
Szabó, C
机构：
[1] Childrens Hosp, Med Ctr, Div Crit Care, Cincinnati, OH 45229 USA
[2] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA
[3] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA
来源：
NEUROSCIENCE LETTERS | 1998年 / 248卷 / 01期
关键词：
neuronal nitric oxide synthase; peroxynitrite; poly(ADP-ribose) synthetase; cerebral ischemia; reperfusion;
D O I：
10.1016/S0304-3940(98)00224-9
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
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. (C) 1998 Elsevier Science Ireland Ltd.
引用
收藏
页码：41 / 44
页数：4
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