Resveratrol induces apoptosis MH7A human rheumatoid arthritis synovial cells in a sirtuin 1-dependent manner

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-XL 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-XL 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.

Resveratrol: A Candidate Drug for Treating Rheumatoid Arthritis

“…Findings by Byun et al (2008) suggest that resveratrol induces apoptosis in fibroblast-like synoviocytes derived from patients with rheumatoid arthritis by activating caspase-8 as a primary target, which cleaves Bid, causing mitochondrial damage that triggers activation of caspase-9 and the effector caspase-3, without affecting the levels of Bax, Bcl-X L , and Bcl-2. This observation contrasts with our finding that resveratrol does not activate caspase-8 in MH7A cells (Nakayama et al, 2010). Thus, resveratrol-induced MH7A cell apoptosis may be mediated via a novel apoptotic pathway.…”

“…Overall, resveratrol appears to downregulate Bcl-X L expression in a sirtuin 1-dependent manner, which promotes Bax-Bax complex, causing disruption of mitochondrial membrane potentials allowing cytochrome c release from the mitochondria. This is followed by activation of caspase-9 and the effector caspase-3, which, in turn, are responsible for apoptosis in MH7A human rheumatoid arthritis synovial cells (Nakayama et al, 2010) (Fig. 7).…”

The natural stilbenoid pinosylvin and activated neutrophils: effects on oxidative burst, protein kinase C, apoptosis and efficiency in adjuvant arthritis

“…The anti-inflammatory activity of pinosylvin, as manifested by reduced hind paw swelling [42] , could be ascribed to several mechanisms, such as the reduced synthesis and release of pro-inflammatory mediators, modified eicosanoid synthesis, decreased activity of immune cells and suppressed activation of nuclear factor κB [22][23][24]43] . Moreover, resveratrol and α-viniferin, compounds that are structurally related to pinosylvin, were found to induce apoptosis of human rheumatoid arthritis synovial cells [44] and prevent tissue destruction in model arthritis [45] . Finally, the action of pinosylvin might involve decreased expression of inducible NO synthase and reduced formation of nitric oxide, as found in macrophages [26,46] .…”

Dimacrolide Sesquiterpene Pyridine Alkaloids from the Stems of <em>Tripterygium regelii</em>

“…Cells were cultured in a Dulbecco's modified Eagle medium (DMEM) supplemented with 10% fetal bovine serum (FBS, Invitrogen, Carlsbad, CA, USA) and 1% penicillin-streptomycin (Sigma, St. Louis, MO, USA) at 37 °C in humidified atmosphere containing 5% CO2. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] was employed to determine the cell viability as described previously [36,37]. Briefly, 5 × 10 3 cells/well MH7A cells (total 100 μL) were cultured in triplicate in a 96-well plate with or without 20 μM compounds for 48 h incubation at 37 °C in humidified atmosphere containing 5% CO2.…”