Inducible hydrogen sulfide synthesis in chondrocytes and mesenchymal progenitor cells: is H2S a novel cytoprotective mediator in the inflamed joint?
Bottom Line: Oxidative stress-induced cell death was significantly inhibited by GYY4137 treatment but increased by pharmacological inhibition of H(2)S synthesis or by CBS/CSE-siRNA treatment.These data suggest CSE is an inducible source of H(2)S in cultured HACs and MPCs.H(2)S may represent a novel endogenous mechanism of cytoprotection in the inflamed joint, suggesting a potential opportunity for therapeutic intervention.
Affiliation: Peninsula Medical School, University of Exeter, St. Luke's Campus, Exeter, Devon, UK.Show MeSH
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Mentions: To confirm the molecular requirement for CSE- and CBS-derived H2S in mediating cytoprotection, we next examined the effects of siRNA-mediated CSE and CBS protein knockdown in chondrocytes. In CSE- and CBS-siRNA-treated cells the cytoprotective effect of L-cysteine against oxidative injury was significantly reduced but preserved in cells transfected with two non-coding siRNA (Fig. 5A and B). Small but statistically significant increases in cell death induced by SIN-1 (Fig. 5A), H2O2 (Fig. 5B) and 4-HNE (Fig. 5C) were observed with CSE and CBS-siRNA treatment, in agreement with the effects of PAG and AOAA in MPCs (Fig. 4C and D). Pharmacological H2S, supplied via GYY4137, further significantly inhibited oxidative stress-induced cell death when added to CSE-treated and CBS-siRNA-treated cells, that is, the lack of enzymatically generated H2S could be overcome by pharmacological H2S.
Affiliation: Peninsula Medical School, University of Exeter, St. Luke's Campus, Exeter, Devon, UK.