Detoxification of methylmercury by hydrogen sulfide-producing enzyme in Mammalian cells.

Methylmercury (MeHg) covalently modifies cellular proteins through their SH groups, resulting in cytotoxicity. We report that cystathionine β-synthase (CBS), which catalyzes the production of hydrogen sulfide, contributes to cellular protection against MeHg. Pretreatment with NaHS or overexpression of CBS reduced MeHg cytotoxicity, whereas transfection with CBS small interfering RNA enhanced MeHg toxicity in human neuroblastoma SH-SY5Y cells. Bismethylmercury sulfide ((MeHg)(2)S) was identified as a metabolite of MeHg in SH-SY5Y cells exposed to MeHg and in the livers of rats treated with MeHg. (MeHg)(2)S had little chemical protein modification capability and little cytotoxicity compared with MeHg in vitro and in vivo.