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 Szabo, László Virág

Research output: Contribution to journalArticle

21 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 (US)
Pages (from-to)1672-1678
Number of pages7
JournalFEBS Letters
Volume582
Issue number12
DOIs
StatePublished - May 28 2008
Externally publishedYes

Fingerprint

Poly(ADP-ribose) Polymerases
Cell death
Protein Kinase C
DNA Damage
Cell Death
DNA
Phosphorylation
Chemical activation
Nitrosoguanidines
Protein C Inhibitor
Phorbol Esters
Thymocytes
Protein Kinase Inhibitors
Necrosis
Poly (ADP-Ribose) Polymerase-1

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Hegedus, C., Lakatos, P., Oláh, G., Tóth, B. I., Gergely, S., Szabó, É., ... Virág, L. (2008). Protein kinase C protects from DNA damage-induced necrotic cell death by inhibiting poly(ADP-ribose) polymerase-1. FEBS Letters, 582(12), 1672-1678. https://doi.org/10.1016/j.febslet.2008.04.023

Protein kinase C protects from DNA damage-induced necrotic cell death by inhibiting poly(ADP-ribose) polymerase-1. / Hegedus, Csaba; Lakatos, Petra; Oláh, Gábor; Tóth, Balázs I.; Gergely, Szabolcs; Szabó, Éva; Bíró, Tamás; Szabo, Csaba; Virág, László.

In: FEBS Letters, Vol. 582, No. 12, 28.05.2008, p. 1672-1678.

Research output: Contribution to journalArticle

Hegedus, C, Lakatos, P, Oláh, G, Tóth, BI, Gergely, S, Szabó, É, Bíró, T, Szabo, C & Virág, L 2008, 'Protein kinase C protects from DNA damage-induced necrotic cell death by inhibiting poly(ADP-ribose) polymerase-1', FEBS Letters, vol. 582, no. 12, pp. 1672-1678. https://doi.org/10.1016/j.febslet.2008.04.023
Hegedus, Csaba ; Lakatos, Petra ; Oláh, Gábor ; Tóth, Balázs I. ; Gergely, Szabolcs ; Szabó, Éva ; Bíró, Tamás ; Szabo, Csaba ; Virág, László. / Protein kinase C protects from DNA damage-induced necrotic cell death by inhibiting poly(ADP-ribose) polymerase-1. In: FEBS Letters. 2008 ; Vol. 582, No. 12. pp. 1672-1678.
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