DNA strand breakage and activation of poly-ADP ribosyltransferase

A cytotoxic pathway triggered by peroxynitrite

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205 Citations (Scopus)

Abstract

Peroxynitrite is a reactive oxidant produced from nitric oxide (NO) and superoxide. Although its reactivity and decomposition are very much dependent on the constituents of the cellular environment, peroxynitrite is considered a potent oxidant that reacts with proteins, lipids, and DNA. Inasmuch as peroxynitrite is formed in many pathophysiological conditions that are associated with NO and/or superoxide overproduction, the investigation of the cytotoxic pathways triggered by peroxynitrite is of major importance. Here we review the evidence that peroxynitrite is a potent initiator of DNA strand breakage, which is an obligatory stimulus for the activation of the nuclear enzyme poly ADP ribosyl synthetase (PARS). We present an overview of experimental data that demonstrate or suggest that the peroxynitrite-PARS pathway, by leading to cell necrosis or apoptosis, contributes to cellular injury in a number of pathophysiological conditions including shock and inflammation, pancreatic islet cell destruction, and diabetes, stroke, and neurodegenerative disorders, as well as the toxic effects of various environmental oxidants or cytotoxic drugs.

Original languageEnglish (US)
Pages (from-to)855-869
Number of pages15
JournalFree Radical Biology and Medicine
Volume21
Issue number6
DOIs
StatePublished - 1996
Externally publishedYes

Fingerprint

ADP Ribose Transferases
Peroxynitrous Acid
Chemical activation
DNA
Oxidants
Ligases
Islets of Langerhans
Superoxides
Adenosine Diphosphate
Nitric Oxide
Enzyme Activation
Poisons
Medical problems
Neurodegenerative Diseases
Shock
Necrosis
Stroke
Apoptosis
Inflammation
Decomposition

Keywords

  • 3-Amimobenzamide
  • Diabetes
  • Endotoxin
  • Free radical
  • Inflammation
  • Mitochondrial respiration
  • Nicotinamide
  • Nitric oxide
  • Peroxynitrite
  • Poly-ADP ribosyl synthetase
  • Septic shock
  • Stroke
  • Superoxide

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

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title = "DNA strand breakage and activation of poly-ADP ribosyltransferase: A cytotoxic pathway triggered by peroxynitrite",
abstract = "Peroxynitrite is a reactive oxidant produced from nitric oxide (NO) and superoxide. Although its reactivity and decomposition are very much dependent on the constituents of the cellular environment, peroxynitrite is considered a potent oxidant that reacts with proteins, lipids, and DNA. Inasmuch as peroxynitrite is formed in many pathophysiological conditions that are associated with NO and/or superoxide overproduction, the investigation of the cytotoxic pathways triggered by peroxynitrite is of major importance. Here we review the evidence that peroxynitrite is a potent initiator of DNA strand breakage, which is an obligatory stimulus for the activation of the nuclear enzyme poly ADP ribosyl synthetase (PARS). We present an overview of experimental data that demonstrate or suggest that the peroxynitrite-PARS pathway, by leading to cell necrosis or apoptosis, contributes to cellular injury in a number of pathophysiological conditions including shock and inflammation, pancreatic islet cell destruction, and diabetes, stroke, and neurodegenerative disorders, as well as the toxic effects of various environmental oxidants or cytotoxic drugs.",
keywords = "3-Amimobenzamide, Diabetes, Endotoxin, Free radical, Inflammation, Mitochondrial respiration, Nicotinamide, Nitric oxide, Peroxynitrite, Poly-ADP ribosyl synthetase, Septic shock, Stroke, Superoxide",
author = "Csaba Szabo",
year = "1996",
doi = "10.1016/0891-5849(96)00170-0",
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T1 - DNA strand breakage and activation of poly-ADP ribosyltransferase

T2 - A cytotoxic pathway triggered by peroxynitrite

AU - Szabo, Csaba

PY - 1996

Y1 - 1996

N2 - Peroxynitrite is a reactive oxidant produced from nitric oxide (NO) and superoxide. Although its reactivity and decomposition are very much dependent on the constituents of the cellular environment, peroxynitrite is considered a potent oxidant that reacts with proteins, lipids, and DNA. Inasmuch as peroxynitrite is formed in many pathophysiological conditions that are associated with NO and/or superoxide overproduction, the investigation of the cytotoxic pathways triggered by peroxynitrite is of major importance. Here we review the evidence that peroxynitrite is a potent initiator of DNA strand breakage, which is an obligatory stimulus for the activation of the nuclear enzyme poly ADP ribosyl synthetase (PARS). We present an overview of experimental data that demonstrate or suggest that the peroxynitrite-PARS pathway, by leading to cell necrosis or apoptosis, contributes to cellular injury in a number of pathophysiological conditions including shock and inflammation, pancreatic islet cell destruction, and diabetes, stroke, and neurodegenerative disorders, as well as the toxic effects of various environmental oxidants or cytotoxic drugs.

AB - Peroxynitrite is a reactive oxidant produced from nitric oxide (NO) and superoxide. Although its reactivity and decomposition are very much dependent on the constituents of the cellular environment, peroxynitrite is considered a potent oxidant that reacts with proteins, lipids, and DNA. Inasmuch as peroxynitrite is formed in many pathophysiological conditions that are associated with NO and/or superoxide overproduction, the investigation of the cytotoxic pathways triggered by peroxynitrite is of major importance. Here we review the evidence that peroxynitrite is a potent initiator of DNA strand breakage, which is an obligatory stimulus for the activation of the nuclear enzyme poly ADP ribosyl synthetase (PARS). We present an overview of experimental data that demonstrate or suggest that the peroxynitrite-PARS pathway, by leading to cell necrosis or apoptosis, contributes to cellular injury in a number of pathophysiological conditions including shock and inflammation, pancreatic islet cell destruction, and diabetes, stroke, and neurodegenerative disorders, as well as the toxic effects of various environmental oxidants or cytotoxic drugs.

KW - 3-Amimobenzamide

KW - Diabetes

KW - Endotoxin

KW - Free radical

KW - Inflammation

KW - Mitochondrial respiration

KW - Nicotinamide

KW - Nitric oxide

KW - Peroxynitrite

KW - Poly-ADP ribosyl synthetase

KW - Septic shock

KW - Stroke

KW - Superoxide

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