Methylmercury alters the tyrosination status of tubulin in the brains of acutely intoxicated rats.

Tyrosination/detyrosination, a post-translational modification at the carboxyl terminus of alpha-tubulin, was investigated in the brain cytosol fraction of rats treated with methylmercury (MeHg) chloride (10 mg/kg per day, for 7 days). The amount of detyrosinated tubulin species, determined as the incorporation of 14C-tyrosine at the carboxyl-terminal end of alpha-tubulin, was significantly decreased throughout the experimental period of MeHg intoxication. Furthermore, the activity of tubulin-tyrosine ligase, as well as the amounts of tyrosinatable tubulin determined and calculated by a method involving pancreatic carboxypeptidase A, also decreased in the latent and symptomatic periods. Tubulin-tyrosine carboxypeptidase activity did not change during the MeHg intoxication. The total amounts of alpha- and beta-tubulins, as determined by densitometry and immunoblotting, did not show significant changes during the intoxication. These results suggest that MeHg treatment may produce perturbation of cellular activities associated with the tubulin/microtubule system by altering the tyrosination status of tubulin in the rat brain.