Protein kinase C protects from DNA damage-induced necrotic cell death by inhibiting poly(ADP-ribose) polymerase-1

Csaba Hegedus, Petra Lakatos, Gábor Oláh, Balázs I. Tóth, Szabolcs Gergely, Éva Szabó, Tamás Bíró, Csaba Szabó, László Virág

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22 Citations (Scopus)

Abstract

The goal of the current study, conducted in freshly isolated thymocytes was (1) to investigate the possibility that the activation of poly(ADP-ribose) polymerase-1 (PARP-1) in an intact cell can be regulated by protein kinase C (PKC) mediated phosphorylation and (2) to examine the consequence of this regulatory mechanism in the context of cell death induced by the genotoxic agent. In cells stimulated by the PKC activating phorbol esters, DNA breakage was unaffected, PARP-1 was phosphorylated, 1-methyl-3-nitro-1-nitrosoguanidine-induced PARP activation and cell necrosis were suppressed, with all these effects attenuated by the PKC inhibitors GF109203X or Gö6976. Inhibition of cellular PARP activity by PKC-mediated phosphorylation may provide a plausible mechanism for the previously observed cytoprotective effects of PKC activators.

Original languageEnglish
Pages (from-to)1672-1678
Number of pages7
JournalFEBS letters
Volume582
Issue number12
DOIs
Publication statusPublished - May 28 2008

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Keywords

  • 1-Methyl-3-nitro-1-nitrosoguanidine
  • Apoptosis
  • Cytotoxicity
  • Necrosis
  • Poly(ADP-ribose) polymerase-1
  • Protein kinase C

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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