TY - JOUR
T1 - Role of peroxynitrite and neuronal nitric oxide synthase in the activation of poly(ADP-ribose) synthetase in a murine model of cerebral ischemia-reperfusion
AU - Endres, Matthias
AU - Scott, Gwen
AU - Namura, Shobu
AU - Salzman, Andrew L.
AU - Huang, Paul L.
AU - Moskowitz, Michael A.
AU - Szabó, Csaba
N1 - Funding Information:
The authors thank Professor Kunihiro Ueda for the kind gift of the polyclonal ADP-ribose antibody. This work was supported by Massachusetts General Hospital Interdepartmental Stroke Project Grants from the National Institutes of Health (NS10828, M.A.M.), the Deutsche Forschungsgemeinschaft (En343/1-1, M.E.), the Uehara Memorial Foundation (S.N.), and the Octamer Research Foundation, (Mill Valley, CA) to G.S.
PY - 1998/5/22
Y1 - 1998/5/22
N2 - 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.
AB - 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.
KW - Cerebral ischemia
KW - Neuronal nitric oxide synthase
KW - Peroxynitrite
KW - Poly(ADP-ribose) synthetase
KW - Reperfusion
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U2 - 10.1016/S0304-3940(98)00224-9
DO - 10.1016/S0304-3940(98)00224-9
M3 - Article
C2 - 9665659
AN - SCOPUS:0032557410
SN - 0304-3940
VL - 248
SP - 41
EP - 44
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 1
ER -