Differential effects of methylmercury on the phosphorylation of protein species in the brain of acutely intoxicated rats.

The in vivo effect of methylmercury (MeHg) on the phosphorylation in vitro of the brain cytosol fraction was examined in acutely poisoned rats (10 mg/kg/day, for 7 days). The total phosphorylation activity, determined in the presence or absence of protein kinase effectors (Ca2+ and cAMP) and substrates (casein, histone and protein kinase C substrate), did not markedly change with the progress of intoxication. Two-dimensional electrophoretic analysis of the phosphorylated cytosol fractions from control and MeHg-treated rats revealed that (1) the extents of phosphorylation of the 24 major protein species in the control rats differed greatly from each other, (2) the effect of MeHg on the phosphorylation was not uniform regarding the individual 24 proteins or the period of intoxication, and (3) in the symptomatic period, many protein species including tubulin subunits showed elevated phosphorylation, while a few protein species showed decreased phosphorylation. These results suggest that the neurotoxic action of MeHg could be mediated through, at least in part, the modification of functional protein species due to excess phosphorylation that leads to impairment of the normal cellular processes.