Poly(ADP-ribose) polymerase activation by reactive nitrogen species - Relevance for the pathogenesis of inflammation

Csaba Szabo

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

Oxidative and nitrosative stress triggers DNA strand breakage, which then activates the nuclear enzyme poly(ADP-ribose) polymerase (PARP). Nitrogen-derived reactive oxidant species capable of involving DNA single strand breakage and PARP activation include peroxynitrite (the reaction product of nitric oxide and superoxide), but not nitric oxide per se. Activation of PARP may dramatically lower 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. Here we review the role of reactive nitrogen species in the process of PARP activation, followed by the effect of pharmacological inhibition or genetic inactivation of PARP on the course of various forms of inflammation.

Original languageEnglish (US)
Pages (from-to)169-179
Number of pages11
JournalNitric Oxide - Biology and Chemistry
Volume14
Issue number2 SPEC. ISS.
DOIs
StatePublished - Mar 2006
Externally publishedYes

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Keywords

  • Arthritis
  • Colitis
  • Nitric oxide
  • Peroxynitrite
  • Sepsis
  • Superoxide

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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