Resveratrol induces apoptosis MH7A human rheumatoid arthritis synovial cells in a sirtuin 1-dependent manner.
Resveratrol, a phytoalexin, reduced the viability of MH7A cells, a human rheumatoid arthritis synovial cell line. In the apoptosis assay, resveratrol increased TUNEL-positive cells and stimulated H2A.X phosphorylation. Resveratrol disrupted mitochondrial membrane potentials in MH7A cells and stimulated cytochrome c release from the mitochondria to the cytosol. Resveratrol activated caspase-3 and caspase-9 but not caspase-8 in MH7A cells. Resveratrol upregulated the expression of the NAD-dependent deacetylase sirtuin 1 mRNA and downregulated the expression of the Bcl-X(L) mRNA, and resveratrol-induced MH7A cell death, mitochondrial damage, and caspase-3/-9 activation were prevented by sirtinol, an inhibitor of sirtuin 1. The results of the present study show that resveratrol induces MH7A cell apoptosis by activating caspase-9 and the effector caspase-3 along mitochondrial disruption as a result of reduced Bcl-X(L) expression, allowing cytochrome c release from the mitochondria into the cytosol, in a sirtuin 1-dependent manner. This suggests that resveratrol could suppress hyperplasia of synovial cells, a critical factor of rheumatoid arthritis.
Nakayama
Hiroshi
H
Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
Yaguchi
Takahiro
T
Yoshiya
Shinichi
S
Nishizaki
Tomoyuki
T
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology*; D001549:Benzamides / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009284:Naphthols / Q000494:pharmacology; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D015854:Up-Regulation / Q000187:drug effects; D051020:bcl-X Protein / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001549:Benzamides; D009284:Naphthols; D013267:Stilbenes; D051020:bcl-X Protein; C439060:sirtinol; D045304:Cytochromes c; D053148:Caspase 3; D053453:Caspase 9; D056564:Sirtuin 1; D000077185:Resveratrol