title: Involvement of reactive persulfides in biological bismethylmercury sulfide formation.
abstract: Bismethylmercury sulfide (MeHg)2S has been found to be a detoxified metabolite of methylmercury (MeHg) that is produced by SH-SY5Y cells and in livers of rats exposed to MeHg. (MeHg)2S could be formed through the interactions between MeHg and sulfur species such as hydrogen sulfide (H2S or HS(-)), but the origin of its sulfur has not been fully identified. We herein examined the formation of (MeHg)2S through interactions between MeHg and persulfides, polysulfides, and protein preparations. Investigations using HPLC/atomic absorption spectrophotometry and EI-MS revealed that NaHS and Na2S4 react readily with MeHg to give (MeHg)2S, and similar results were found using GSH persulfide (GSSH) formed endogenously or generated enzymatically in vitro. (MeHg)2S was also formed by incubation of MeHg with liver and heart cytosolic fractions prepared from wild-type mice but not with those from mice lacking cystathionine γ-lyase (CSE) that catalyzes the formation of cysteine persulfide. Consistent with this, (MeHg)2S was detected in a variety of tissues taken from wild-type mice intraperitoneally injected with MeHg in vivo but not in those from MeHg-injected CSE knockout mice. By separating liver fractions by column chromatography, we found numerous proteins that contain persulfides: one of the proteins was identified as being glutathione S-transferase pi 1. These results indicate that the formation of (MeHg)2S can be attributed to interactions between MeHg and endogenous free persulfide species, as well as protein-bound cysteine persulfide.
authors: Yumi
authors: Y
authors: Abiko
authors: Eiko
authors: E
authors: Yoshida
authors: §Department of Biochemistry, Keio University School of Pharmaceutical Sciences, Tokyo 105-8512, Japan.
authors: Isao
authors: I
authors: Ishii
authors: ∥Department of Chemistry, Sonoma State University, Rohnert Park, California 94928, United States.
authors: Jon M
authors: JM
authors: Fukuto
authors: ⊥Department of Environmental Health Sciences and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors: Takaaki
authors: T
authors: Akaike
authors: Yoshito
authors: Y
authors: Kumagai
mesh_terms: D000818:Animals; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism; D051549:Glutathione S-Transferase pi / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008767:Methylmercury Compounds / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008970:Molecular Weight; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013440:Sulfides / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D008767:Methylmercury Compounds; D011994:Recombinant Proteins; D013440:Sulfides; C051552:persulfides; C108833:methylmercury sulfide; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi