Nitric oxide, peroxynitrite and poly (adpribose) synthetase activation: role in the suppression of cellular energetics

Csaba Szabo

Research output: Contribution to journalArticle

Abstract

Our current results demonstrate that peroxynitrite, a cytotoxic oxidant, induces DNA strand-breakage, which activates the nuclear enzyme poly (ADP-ribose) synthetase (PARS) and initiates an energy consuming, inefficient repair cycle, which leads to cellular dysfunction (Szabó, Free Rad Biol Med, 21: 855, '96). While peroxynitrite-induced cellular energetic changes (suppression of mitochondrial respiration, decrease in NAD+, and decrease in cellular ATP) were ameliorated by inhibition of the activity of PARS, the cellular energetic derangement by "pure" NO (in the absence of superoxide generators) was not prevented by inhibition of PARS. These findings are in agreement with data showing that peroxynitrite, but not NO per se, initiates DNA single strand breakage. At high peroxynitrite concentrations, the protection provided by PARS inhibition wanes. Thus, there are distinct NO- and peroxynitrite- induced pathways of metabolic inhibition, the former one being PARS-independent, while the latter one involving both PARS-dependent PARS-independent components. In addition to the in vitro data, in vivo data will also be presented to show peroxynitrite production and protection by PARS inhibition against the tissue injury during ischemia-reperfusion and in inflammation.

Original languageEnglish (US)
JournalBiochemical Society Transactions
Volume25
Issue number3
StatePublished - 1997
Externally publishedYes

Fingerprint

Adenosine Diphosphate Ribose
Poly Adenosine Diphosphate Ribose
Peroxynitrous Acid
Ligases
Nitric Oxide
Chemical activation
DNA
Metabolic Networks and Pathways
Reperfusion Injury
Oxidants
Superoxides
NAD
Respiration
Repair
Adenosine Triphosphate
Tissue
Inflammation

ASJC Scopus subject areas

  • Biochemistry

Cite this

@article{d50f7a1c40284905bbb8fbccd4aa526e,
title = "Nitric oxide, peroxynitrite and poly (adpribose) synthetase activation: role in the suppression of cellular energetics",
abstract = "Our current results demonstrate that peroxynitrite, a cytotoxic oxidant, induces DNA strand-breakage, which activates the nuclear enzyme poly (ADP-ribose) synthetase (PARS) and initiates an energy consuming, inefficient repair cycle, which leads to cellular dysfunction (Szab{\'o}, Free Rad Biol Med, 21: 855, '96). While peroxynitrite-induced cellular energetic changes (suppression of mitochondrial respiration, decrease in NAD+, and decrease in cellular ATP) were ameliorated by inhibition of the activity of PARS, the cellular energetic derangement by {"}pure{"} NO (in the absence of superoxide generators) was not prevented by inhibition of PARS. These findings are in agreement with data showing that peroxynitrite, but not NO per se, initiates DNA single strand breakage. At high peroxynitrite concentrations, the protection provided by PARS inhibition wanes. Thus, there are distinct NO- and peroxynitrite- induced pathways of metabolic inhibition, the former one being PARS-independent, while the latter one involving both PARS-dependent PARS-independent components. In addition to the in vitro data, in vivo data will also be presented to show peroxynitrite production and protection by PARS inhibition against the tissue injury during ischemia-reperfusion and in inflammation.",
author = "Csaba Szabo",
year = "1997",
language = "English (US)",
volume = "25",
journal = "Biochemical Society Transactions",
issn = "0300-5127",
publisher = "Portland Press Ltd.",
number = "3",

}

TY - JOUR

T1 - Nitric oxide, peroxynitrite and poly (adpribose) synthetase activation

T2 - role in the suppression of cellular energetics

AU - Szabo, Csaba

PY - 1997

Y1 - 1997

N2 - Our current results demonstrate that peroxynitrite, a cytotoxic oxidant, induces DNA strand-breakage, which activates the nuclear enzyme poly (ADP-ribose) synthetase (PARS) and initiates an energy consuming, inefficient repair cycle, which leads to cellular dysfunction (Szabó, Free Rad Biol Med, 21: 855, '96). While peroxynitrite-induced cellular energetic changes (suppression of mitochondrial respiration, decrease in NAD+, and decrease in cellular ATP) were ameliorated by inhibition of the activity of PARS, the cellular energetic derangement by "pure" NO (in the absence of superoxide generators) was not prevented by inhibition of PARS. These findings are in agreement with data showing that peroxynitrite, but not NO per se, initiates DNA single strand breakage. At high peroxynitrite concentrations, the protection provided by PARS inhibition wanes. Thus, there are distinct NO- and peroxynitrite- induced pathways of metabolic inhibition, the former one being PARS-independent, while the latter one involving both PARS-dependent PARS-independent components. In addition to the in vitro data, in vivo data will also be presented to show peroxynitrite production and protection by PARS inhibition against the tissue injury during ischemia-reperfusion and in inflammation.

AB - Our current results demonstrate that peroxynitrite, a cytotoxic oxidant, induces DNA strand-breakage, which activates the nuclear enzyme poly (ADP-ribose) synthetase (PARS) and initiates an energy consuming, inefficient repair cycle, which leads to cellular dysfunction (Szabó, Free Rad Biol Med, 21: 855, '96). While peroxynitrite-induced cellular energetic changes (suppression of mitochondrial respiration, decrease in NAD+, and decrease in cellular ATP) were ameliorated by inhibition of the activity of PARS, the cellular energetic derangement by "pure" NO (in the absence of superoxide generators) was not prevented by inhibition of PARS. These findings are in agreement with data showing that peroxynitrite, but not NO per se, initiates DNA single strand breakage. At high peroxynitrite concentrations, the protection provided by PARS inhibition wanes. Thus, there are distinct NO- and peroxynitrite- induced pathways of metabolic inhibition, the former one being PARS-independent, while the latter one involving both PARS-dependent PARS-independent components. In addition to the in vitro data, in vivo data will also be presented to show peroxynitrite production and protection by PARS inhibition against the tissue injury during ischemia-reperfusion and in inflammation.

UR - http://www.scopus.com/inward/record.url?scp=33745117320&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745117320&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:33745117320

VL - 25

JO - Biochemical Society Transactions

JF - Biochemical Society Transactions

SN - 0300-5127

IS - 3

ER -