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

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

doi:10.1016/j.febslet.2008.04.023

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Volume 582, Issue 12 , Pages 1672-1678, 28 May 2008

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

Edited by Varda Rotter

Csaba Hegedűs
- Department of Medical Chemistry, Medical and Health Science Center, University of Debrecen, H-4012 Debrecen, Nagyerdei krt. 98, Hungary
Petra Lakatos
- Department of Medical Chemistry, Medical and Health Science Center, University of Debrecen, H-4012 Debrecen, Nagyerdei krt. 98, Hungary
Gábor Oláh
- Department of Surgery, University of Medicine and Dentistry of New Jersey, Newark, NJ, 07103, USA
Balázs I. Tóth
- Department of Physiology, Medical and Health Science Center, University of Debrecen, H-4012 Debrecen, Nagyerdei krt. 98, Hungary
Szabolcs Gergely
- Department of Cardiology, Medical and Health Science Center, University of Debrecen, H-4012 Debrecen, Nagyerdei krt. 98, Hungary
Éva Szabó
- Department of Dermatology, Medical and Health Science Center, University of Debrecen, H-4012 Debrecen, Nagyerdei krt. 98, Hungary
Tamás Bíró
- Department of Physiology, Medical and Health Science Center, University of Debrecen, H-4012 Debrecen, Nagyerdei krt. 98, Hungary
Csaba Szabó
- Department of Surgery, University of Medicine and Dentistry of New Jersey, Newark, NJ, 07103, USA
László Virág
- Department of Medical Chemistry, Medical and Health Science Center, University of Debrecen, H-4012 Debrecen, Nagyerdei krt. 98, Hungary
- Cell Biology and Signaling Research Group of the Hungarian Academy of Sciences, Debrecen, Hungary
- Corresponding author. Address: Department of Medical Chemistry, Medical and Health Science Center, University of Debrecen, Élettudományi Épület 3.311, Nagyerdei krt. 98, H-4032 Debrecen, Hungary. Fax: +36 52 412 566.

Received 25 February 2008; received in revised form 11 April 2008; accepted 13 April 2008. published online 24 April 2008.

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.

Abbreviations: DMSO, dimethylsulfoxide, DTT, dithiothreitol, MNNG, 1-methyl-3-nitro-1-nitrosoguanidine, MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, PARP, poly(ADP-ribose) polymerase, PI, propidium iodide, PMA, phorbol 12-myristate 13-acetate, PKC, protein kinase C