RRC ID 43550
Author Nakayama H, Yaguchi T, Yoshiya S, Nishizaki T.
Title Resveratrol induces apoptosis MH7A human rheumatoid arthritis synovial cells in a sirtuin 1-dependent manner.
Journal Rheumatol Int
Abstract 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.
Volume 32(1)
Pages 151-7
Published 2012-1
DOI 10.1007/s00296-010-1598-8
PMID 20697895
PMC PMC3253293
MeSH Anti-Inflammatory Agents, Non-Steroidal / pharmacology Apoptosis / drug effects* Arthritis, Rheumatoid / metabolism* Arthritis, Rheumatoid / pathology* Benzamides / pharmacology Caspase 3 / metabolism Caspase 9 / metabolism Cell Line Cytochromes c / metabolism Humans Mitochondria / metabolism Naphthols / pharmacology Resveratrol Sirtuin 1 / antagonists & inhibitors Sirtuin 1 / metabolism* Stilbenes / pharmacology* Synovial Membrane / drug effects Synovial Membrane / metabolism* Synovial Membrane / pathology* Up-Regulation / drug effects bcl-X Protein / metabolism
IF 2.2
Times Cited 35
WOS Category RHEUMATOLOGY
Resource
Human and Animal Cells