Methylmercury toxicity in dissociated rat brain neurons: modification by l-cysteine and trimethylbenzylmercaptan and comparison with dimethylmercury and N-ethylmaleimide

Abstract

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.