Role of poly(ADP-ribose) synthetase in inflammation and ischaemia- reperfusion

Csaba Szabo, Valina L. Dawson

Research output: Contribution to journalArticle

630 Citations (Scopus)

Abstract

Oxidative and nitrosative stress can trigger DNA strand breakage, which then activates the nuclear enzyme poly(ADP-ribose) synthetase (PARS). This enzyme has also been termed poly(ADP-ribose) polymerase (PARP) or poly(ADP- ribose) transferase (pADPRT). Rapid activation of the enzyme depletes the intracellular concentration of its substrate, nicotinamide adenine dinucleotide, thus slowing the rate of glycolysis, electron transport and subsequently ATP formation. This process can result in cell dysfunction and cell death. In this article, Csaba Szabo and Valina Dawson overview the impact of pharmacological inhibition or genetic inactivation of PARS on the course of oxidant-induced cell death in vitro, and in inflammation and reperfusion injury in vivo. A major trigger for DNA damage in pathophysiological conditions is peroxynitrite, a cytotoxic oxidant formed by the reaction between the free radicals nitric oxide and superoxide. The pharmacological inhibition of poly(ADP-ribose) synthetase is a novel approach for the experimental therapy of various forms of inflammation and shock, stroke, myocardial and intestinal ischaemia-reperfusion, and diabetes mellitus.

Original languageEnglish (US)
Pages (from-to)287-298
Number of pages12
JournalTrends in Pharmacological Sciences
Volume19
Issue number7
DOIs
StatePublished - Jul 1 1998
Externally publishedYes

Fingerprint

Poly Adenosine Diphosphate Ribose
Ligases
Reperfusion
Ischemia
Poly(ADP-ribose) Polymerases
Cell death
Inflammation
Oxidants
Cell Death
Enzymes
Pharmacology
Investigational Therapies
Peroxynitrous Acid
Enzyme Activation
DNA
Glycolysis
Medical problems
Electron Transport
Reperfusion Injury
Superoxides

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Role of poly(ADP-ribose) synthetase in inflammation and ischaemia- reperfusion. / Szabo, Csaba; Dawson, Valina L.

In: Trends in Pharmacological Sciences, Vol. 19, No. 7, 01.07.1998, p. 287-298.

Research output: Contribution to journalArticle

Szabo, Csaba ; Dawson, Valina L. / Role of poly(ADP-ribose) synthetase in inflammation and ischaemia- reperfusion. In: Trends in Pharmacological Sciences. 1998 ; Vol. 19, No. 7. pp. 287-298.
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