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

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• 作者：Csaba Hegedű ; s ; Petra Lakatos ; Gá ; bor Olá ; h ; Balá ; zs I. T&#xf3 ; th ; Szabolcs Gergely ; É ; va Szab&#xf3 ; Tamá ; s Bí ; r&#xf3 ; Csaba Szab&#xf3 ; Lá ; szl&#xf3 ; Virá ; g
• 关键词：Poly(ADP-ribose) polymerase-1 ; Protein kinase C ; Cytotoxicity ; Necrosis ; Apoptosis ; 1-Methyl-3-nitro-1-nitrosoguanidine
• 刊名：FEBS Letters
• 出版年：2008
• 期刊代码：70_00145793
• 类别：bio
• 出版时间：28 May 2008
• 卷：582
• 期：12
• 页码：1672-1678
• 文件大小：236 K

摘要

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.