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 v itro of the brain cytosol fraction was examined in acutely poisoned ra ts (10 mg/kg/day, for 7 days). The total phosphorylation activity, det ermined in the presence or absence of protein kinase effecters (Ca2+ a nd cAMP) and substrates (casein, histone and protein kinase C substrat e), did not markedly change with the progress of intoxication. Two-dim ensional electrophoretic analysis of the phosphorylated cytosol fracti ons from control and MeHg-treated rats revealed that (1) the extents o f phosphorylation of the 24 major protein species in the control rats differed greatly from each other, (2) the effect of MeHg on the phosph orylation was not uniform regarding the individual 24 proteins or the period of intoxication, and (3) in the symptomatic period, many protei n species including tubulin subunits showed elevated phosphorylation, while a few protein species showed decreased phosphorylation. These re sults suggest that the neurotoxic action of MeHg could be mediated thr ough, at least in part, the modification of functional protein species due to excess phosphorylation that leads to impairment of the normal cellular processes.