Resveratrol delays replicative senescence of human mesothelial cells via mobilization of antioxidative and DNA repair mechanisms

Resveratrol (3,4′,5-trihydroxy-trans-stilbene; RVT) is a natural phytoestrogen known to modulate the rate of senescence in cultured cells. The mechanism by which RVT affects this process is still elusive. In this paper we used human peritoneal mesothelial cells (HPMCs) to examine the effect of RVT (...

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Veröffentlicht in:Free radical biology & medicine 2012-06, Vol.52 (11-12), p.2234-2245
Hauptverfasser: Mikuła-Pietrasik, Justyna, Kuczmarska, Angelika, Rubiś, Błażej, Filas, Violetta, Murias, Marek, Zieliński, Paweł, Piwocka, Katarzyna, Książek, Krzysztof
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Sprache:eng
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Zusammenfassung:Resveratrol (3,4′,5-trihydroxy-trans-stilbene; RVT) is a natural phytoestrogen known to modulate the rate of senescence in cultured cells. The mechanism by which RVT affects this process is still elusive. In this paper we used human peritoneal mesothelial cells (HPMCs) to examine the effect of RVT (0.5 and 10μM) on their growth and senescence, with particular emphasis paid to parameters associated with oxidative stress. The results showed that RVT used at a concentration of 0.5μM (but not at 10μM) markedly improved HPMC growth capacity, as evidenced by elevated expression of PCNA antigen, augmented fraction of cells in the S phase of the cell cycle, and increased number of divisions achieved before senescence. These effects coincided with diminished expression and activity of senescence-associated β-galactosidase but were not associated with changes in the telomere length and an incidence of apoptosis. Moreover cells exposed to 0.5μM RVT were characterized by increased release of reactive oxygen species, which was accompanied by up-regulated biogenesis of mitochondria and collapsed mitochondrial membrane potential. At the same time, they displayed increased activity of superoxide dismutase and reduced DNA damage (8-OH-dG and γ-H2A.X level). The efficiency of 8-OH-dG repair was increased which could be related to increased activity of DNA glycosylase I (hOgg1). As shown using RT-PCR, expression of hOgg1 mRNA in these cells was markedly elevated. Collectively, our results indicate that delayed senescence of HPMCs exposed to RVT may be associated with mobilization of antioxidative and DNA repair mechanisms. [Display omitted] ► Resveratrol improves proliferative capacity of human peritoneal mesothelial cells. ► Resveratrol delays the onset of senescence in human peritoneal mesothelial cells. ► Resveratrol mobilizes antioxidative and DNA repair mechanisms.
ISSN:0891-5849
1873-4596
DOI:10.1016/j.freeradbiomed.2012.03.014