Laboratory of Cellular Signaling, Faculty of Integrated Arts and Sciences, The University of Tokushima, Minami-Jyozanjima 1-1, Tokushima 770-8502, Japan.
Environ Toxicol Pharmacol. 1998 Dec 1;6(4):221-7. doi: 10.1016/s1382-6689(98)00038-6.
The effects of methylmercury (MeHg) on dissociated rat cerebellar neurons were compared with those of MeHg conjugated with l-cysteine (MeHg-Cys conjugate), dimethylmercury (DiMeHg), N-ethylmaleimide (NEM) and ionomycin using a flow cytometer and two fluorescent dyes, fluo-3-AM and ethidium bromide. The efficacies of MeHg to increase intracellular concentration of Ca(2+) ([Ca(2+)]i) and to decrease cell viability were greatly reduced by conjugating MeHg with l-cysteine. It was not due to a decreased lipophilic property of MeHg-Cys because the conjugation of MeHg with trimethylbenzylmercaptane, a lipophilic substance, also reduced the efficacies. It seems that the reactivity of MeHg to SH-groups is responsible for the MeHg-induced toxicity since NEM increased [Ca(2+)]i and decreased cell viability while DiMeHg did not significantly affect them. However, the toxicity of MeHg was not explained only by the reactivity of MeHg to SH-groups since NEM-induced changes in fluo-3 and ethidium fluorescence were different from MeHg-induced ones. Ionomycin-induced changes in those fluorescence were also different although ionomycin decreased cell viability after increasing [Ca(2+)]i. Therefore, it is suggested that the mechanism of MeHg toxicity is more complicated than those of NEM and ionomycin.
采用流式细胞仪和两种荧光染料（Fluo-3-AM 和溴化乙锭），比较了甲基汞（MeHg）与半胱氨酸（MeHg-Cys 缀合物）、二甲基汞（DiMeHg）、N-乙基马来酰亚胺（NEM）和离子霉素对分离的大鼠小脑神经元的影响。MeHg 与半胱氨酸缀合后，增加细胞内钙离子浓度 ([Ca(2+)]i) 和降低细胞活力的效果大大降低。这并不是因为 MeHg-Cys 的亲脂性降低，因为 MeHg 与三甲苄基硫醇（一种亲脂性物质）的缀合也降低了效果。似乎 MeHg 与 SH 基团的反应性是导致 MeHg 诱导毒性的原因，因为 NEM 增加了 [Ca(2+)]i 并降低了细胞活力，而 DiMeHg 则没有显著影响。然而，MeHg 的毒性不能仅用 MeHg 与 SH 基团的反应性来解释，因为 NEM 诱导的 Fluoro-3 和溴化乙锭荧光的变化与 MeHg 诱导的变化不同。尽管离子霉素在增加 [Ca(2+)]i 后降低了细胞活力，但离子霉素诱导的这些荧光变化也不同。因此，建议 MeHg 毒性的机制比 NEM 和离子霉素的机制更复杂。
