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. Virag

Research output: Contribution to journalArticle

65 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 2005

Fingerprint

Oxidative stress
Poly(ADP-ribose) Polymerases
Cell death
Adenosine Diphosphate
Reperfusion
Oxidative Stress
Cell Death
Chemical activation
Adenosine Diphosphate Ribose
Signal transduction
DNA Breaks
Calcium Signaling
DNA
Transcription
Medical problems
Nuclear Proteins
Brain Ischemia
Metabolism
DNA Repair
NAD

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

Cite this

Pathophysiologic role of oxidative stress-induced poly(ADP-ribose) polymerase-1 activation : Focus on cell death and transcriptional regulation. / Erdélyi, K.; Bakondi, E.; Gergely, P.; Szabó, C.; Virag, L.

In: Cellular and Molecular Life Sciences, Vol. 62, No. 7-8, 04.2005, p. 751-759.

Research output: Contribution to journalArticle

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