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

doi:10.1016/S0304-3940(98)00224-9

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 journal › Article › peer-review

105 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 language	English (US)
Pages (from-to)	41-44
Number of pages	4
Journal	Neuroscience Letters
Volume	248
Issue number	1
DOIs	https://doi.org/10.1016/S0304-3940(98)00224-9
State	Published - May 22 1998
Externally published	Yes

Keywords

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

ASJC Scopus subject areas

General Neuroscience

Access to Document

10.1016/S0304-3940(98)00224-9

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

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.",

keywords = "Cerebral ischemia, Neuronal nitric oxide synthase, Peroxynitrite, Poly(ADP-ribose) synthetase, Reperfusion",

author = "Matthias Endres and Gwen Scott and Shobu Namura and Salzman, \{Andrew L.\} and Huang, \{Paul L.\} and Moskowitz, \{Michael A.\} and Csaba Szab{\'o}",

note = "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.",

year = "1998",

month = may,

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doi = "10.1016/S0304-3940(98)00224-9",

language = "English (US)",

volume = "248",

pages = "41--44",

journal = "Neuroscience Letters",

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

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