Cytoprotective effect of gallotannin in oxidatively stressed HaCaT keratinocytes: The role of poly(ADP-ribose) metabolism

Edina Bakondi, Péter Bai, Katalin Erdélyi, Csaba Szabó, Pál Gergely, László Virág

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Oxidative stress-induced cytotoxicity is mediated in part by accelerated poly-ADP ribosylation. Peroxynitrite and hydrogen peroxide cause DNA breakage triggering the activation of the DNA nick sensor enzyme poly(ADP-ribose) polymerase-1 (PARP-1). Overactivation of PARP-1 leads to cell dysfunction and cell death mainly due to depletion of NAD+ (the substrate of PARP-1) and ATP. PARP-1 attaches most ADP-ribose residues onto itself, leading to downregulation of enzyme activity. Here, we have investigated the role of poly(ADP-ribose) glycohydrolase (PARG), the poly(ADP-ribose)-catabolyzing enzyme in oxidative stress-induced cytotoxicity in HaCaT cells. We have found that inhibition of PARG by gallotannin (GT) (50 μM) provided significant cytoprotection to peroxynitrite- or hydrogen peroxide-treated HaCaT cells, as assessed by lactate dehydrogenase release and propidium iodide uptake (parameters of necrotic cell death) as well as caspase activation (apoptotic parameter). GT pretreatment has also inhibited the depletion of cellular NAD+ pools in hydrogen peroxide- or peroxynitrite-treated HaCaT cells. GT caused the accumulation of poly(ADP-ribose) and concomitant inhibition in cellular PARP activity in oxidatively stressed cells. Therefore, PARG is likely to contribute to maintaining the active state of PARP-1 by continuously removing inhibitory ADP-ribose residues from PARP-1.

Original languageEnglish
Pages (from-to)170-178
Number of pages9
JournalExperimental Dermatology
Volume13
Issue number3
DOIs
Publication statusPublished - Mar 1 2004

Keywords

  • Cytotoxicity
  • Keratinocytes
  • Necrosis
  • Nitric oxide
  • Tannins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

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