title: Detoxification of methylmercury by hydrogen sulfide-producing enzyme in Mammalian cells.
abstract: 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.
authors.affiliation: Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan.
authors.forename: Eiko
authors.initials: E
authors.lastname: Yoshida
authors.forename: Takashi
authors.initials: T
authors.lastname: Toyama
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shinkai
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Sawa
authors.forename: Takaaki
authors.initials: T
authors.lastname: Akaike
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Kumagai
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003541:Cystathionine beta-Synthase / Q000378:metabolism*; D004785:Environmental Pollutants / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008658:Inactivation, Metabolic; D008099:Liver / Q000378:metabolism; D008767:Methylmercury Compounds / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D051379:Mice; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D013440:Sulfides / Q000494:pharmacology
chemical_list: D004785:Environmental Pollutants; D008767:Methylmercury Compounds; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D020011:Protective Agents; D013440:Sulfides; C108833:methylmercury sulfide; D003541:Cystathionine beta-Synthase; C025451:sodium bisulfide; D006862:Hydrogen Sulfide