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

The effects of methylmercury (MeHg) on dissociated rat cerebellar neurons w ere compared with those of MeHg conjugated with L-cysteine (MeHg-Cys conjug ate), 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 Ca2+ ([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 reacti vity of MeHg to SH-groups is responsible for the MeHg-induced toxicity sinc e NEM increased [Ca2+](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 f luo-3 and ethidium fluorescence were different from MeHg-induced ones. Iono mycin-induced changes in those fluorescence were also different although io nomycin decreased cell viability after increasing [Ca2+](i). Therefore, it is suggested that the mechanism of MeHg toxicity is more complicated than t hose of NEM and ionomycin. (C) 1998 Elsevier Science B.V. All rights reserv ed.