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

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

Research output: Contribution to journalArticle

28 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 (US)
Pages (from-to)170-178
Number of pages9
JournalExperimental Dermatology
Volume13
Issue number3
DOIs
StatePublished - Mar 2004
Externally publishedYes

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Hydrolyzable Tannins
Poly Adenosine Diphosphate Ribose
Poly(ADP-ribose) Polymerases
Keratinocytes
Metabolism
Peroxynitrous Acid
Adenosine Diphosphate Ribose
Hydrogen Peroxide
Oxidative stress
Cell death
Cytotoxicity
NAD
Oxidative Stress
Enzyme sensors
Cell Death
Enzymes
Chemical activation
Single-Stranded DNA Breaks
Cytoprotection
Propidium

Keywords

  • Cytotoxicity
  • Keratinocytes
  • Necrosis
  • Nitric oxide
  • Tannins

ASJC Scopus subject areas

  • Dermatology

Cite this

Cytoprotective effect of gallotannin in oxidatively stressed HaCaT keratinocytes : The role of poly(ADP-ribose) metabolism. / Bakondi, Edina; Bai, Péter; Erdélyi, Katalin; Szabo, Csaba; Gergely, Pál; Virág, László.

In: Experimental Dermatology, Vol. 13, No. 3, 03.2004, p. 170-178.

Research output: Contribution to journalArticle

Bakondi, Edina ; Bai, Péter ; Erdélyi, Katalin ; Szabo, Csaba ; Gergely, Pál ; Virág, László. / Cytoprotective effect of gallotannin in oxidatively stressed HaCaT keratinocytes : The role of poly(ADP-ribose) metabolism. In: Experimental Dermatology. 2004 ; Vol. 13, No. 3. pp. 170-178.
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