title: Resveratrol delays replicative senescence of human mesothelial cells via mobilization of antioxidative and DNA repair mechanisms.
abstract: 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 10 μM) 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 0.5 μM (but not at 10 μM) 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 0.5 μM 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.
authors.affiliation: Department of Pathophysiology, Poznań University of Medical Sciences, Święcickiego 6, 60-781 Poznań, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Mikuła-Pietrasik
authors.forename: Angelika
authors.initials: A
authors.lastname: Kuczmarska
authors.forename: Błażej
authors.initials: B
authors.lastname: Rubiś
authors.forename: Violetta
authors.initials: V
authors.lastname: Filas
authors.forename: Marek
authors.initials: M
authors.lastname: Murias
authors.forename: Paweł
authors.initials: P
authors.lastname: Zieliński
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Piwocka
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Książek
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D048708:Cell Growth Processes / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects* / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D013267:Stilbenes; D013482:Superoxide Dismutase; D001616:beta-Galactosidase; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; D000077185:Resveratrol