Pathophysiologic role of oxidative stress-induced poly(ADP-ribose) polymerase-1 activation: Focus on cell death and transcriptional regulation

K. Erdélyi, E. Bakondi, P. Gergely, C. Szabó, L. Virág

Research output: Contribution to journalReview article

68 Citations (Scopus)

Abstract

PARP-1 is a nuclear enzyme activated by DNA breaks. Activated PARP-1 cleaves NAD into nicotinamide and ADP-ribose and polymerizes the latter covalently coupled to nuclear acceptor proteins. Poly(ADP-ribosyl)-ation has been implicated in the regulation of a diverse array of cellular processes ranging from DNA repair, chromatin organization, transcription, replication to protein degradation. On the 'dark side' of poly(ADP-ribosyl)ation, PARP-1 activation has been shown to contribute to tissue injury in shock, diabetes, myocardial or cerebral ischemia reperfusion and various forms of inflammation, as proven by pharmacological studies as well as experiments utilizing PARP-1 knockout animals. To our current knowledge, two mechanisms are responsible for the beneficial effects of PARP inhibitors in inflammatory, neurodegenerative and ischemia-reperfusion-based diseases: (i) inhibition of cell death caused by over-activation of PARP-1; (ii) inhibition of inflammatory signal transduction and production of inflammatory mediators. Here we review the possible regulatory mechanisms (e.g. calcium signaling, metabolism, density-dependent signaling, kinase cascades) of the PARP-1-mediated cell death pathway and discuss recent developments shedding new light on the complex role of PARP-1 in the regulation of the expression of inflammatory mediators.

Original languageEnglish
Pages (from-to)751-759
Number of pages9
JournalCellular and Molecular Life Sciences
Volume62
Issue number7-8
DOIs
Publication statusPublished - Apr 1 2005

Keywords

  • Apoptosis
  • Calcium signal
  • Cytotoxicity
  • DNA damage
  • Mitochondria
  • Necrosis
  • Peroxynitrite
  • Poly(ADP-ribose) polymerase

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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