Bismethylmercury sulfide (MeHg)<inf>2</inf>S 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)<inf>2</inf>S could be formed through the interactions between MeHg and sulfur species such as hydrogen sulfide (H<inf>2</inf>S or HS<sup>-</sup>), but the origin of its sulfur has not been fully identified. We herein examined the formation of (MeHg)<inf>2</inf>S through interactions between MeHg and persulfides, polysulfides, and protein preparations. Investigations using HPLC/atomic absorption spectrophotometry and EI-MS revealed that NaHS and Na<inf>2</inf>S<inf>4</inf> react readily with MeHg to give (MeHg)<inf>2</inf>S, and similar results were found using GSH persulfide (GSSH) formed endogenously or generated enzymatically in vitro. (MeHg)<inf>2</inf>S 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)<inf>2</inf>S 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)<inf>2</inf>S can be attributed to interactions between MeHg and endogenous free persulfide species, as well as protein-bound cysteine persulfide.
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