title: Resveratrol Derivative, 3,3',4,4'-Tetrahydroxy-trans-Stilbene, Retards Senescence of Mesothelial Cells via Hormetic-Like Prooxidative Mechanism.
abstract: There is agreement that the biological properties of additionally hydroxylated analogs of resveratrol (RVT) may be stronger compared with their parent drug. Here we examined the effect of a novel RVT derivative, 3,3',4,4'-tetrahydroxy-trans-stilbene (3,3',4,4'-THS), on the replicative senescence of human peritoneal mesothelial cells. The study showed that 3,3',4,4'-THS improves the cell proliferative capacity and delays their entry into senescence compared with control and RVT-treated cells. The latter coincided with decreased activity of senescence-associated β-galactosidase and p38 mitogen-activated protein kinase. Besides, 3,3',4,4'-THS preserved functionality of the mitochondria in senescent cells, as evidenced according to increased membrane potential and decreased mitochondrial content. In addition, it induced, to a larger extent than RVT, the production of superoxides and nonspecific reactive oxygen species and intensified their removal. This was probably related to the augmented activity of antioxidative systems, including superoxide dismutase, catalase, and reduced glutathione. The magnitude of DNA injury (8-hydroxy-2'-deoxyguanosine, histone γ-H2A.X) in cells treated with 3,3',4,4'-THS was diminished, which coincided with suppression of the DNA damage response transducer, 53BP1. Altogether, our study shows that 3,3',4,4'-THS is a more efficient antisenescence agent than RVT, which may be associated with its stimulatory effect on reactive oxygen species release, which results in a compensatory induction of antioxidants and concomitant suppression of oxidative DNA injury.
authors.affiliation: Laboratory of Gerontology, Department of Pathophysiology, These authors contributed equally to this article.
authors.forename: Justyna
authors.initials: J
authors.lastname: Mikuła-Pietrasik
authors.affiliation: Laboratory of Gerontology, Department of Pathophysiology, These authors contributed equally to this article.
authors.forename: Patrycja
authors.initials: P
authors.lastname: Sosińska
authors.affiliation: Department of Toxicology.
authors.forename: Marek
authors.initials: M
authors.lastname: Murias
authors.affiliation: Department of Informatics and Statistics, and.
authors.forename: Michał
authors.initials: M
authors.lastname: Michalak
authors.affiliation: Department of Chemical Technology of Drugs, Poznań University of Medical Sciences, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Wierzchowski
authors.affiliation: Laboratory of Molecular Bases of Ageing, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Piechota
authors.affiliation: Laboratory of Molecular Bases of Ageing, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Sikora
authors.affiliation: Laboratory of Gerontology, Department of Pathophysiology, krzysztof.ksiazek@ump.edu.pl.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Książek
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D048708:Cell Growth Processes / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D010537:Peritoneum / Q000166:cytology; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D013267:Stilbenes; D002374:Catalase; D013482:Superoxide Dismutase; D048051:p38 Mitogen-Activated Protein Kinases; D001616:beta-Galactosidase; D005978:Glutathione; D000077185:Resveratrol
keywords: Mesothelial cells; Oxidative stress; Replicative senescence; Resveratrol; Stilbenes