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.
Ishida
Y
Y
Department of Biochemistry, Faculty of Science, Niigata University, Japan.
Ichimura
T
T
Sumi
H
H
Horigome
T
T
Omata
S
S
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002268:Carboxypeptidases / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005260:Female; D015151:Immunoblotting; D008767:Methylmercury Compounds / Q000633:toxicity*; D010453:Peptide Synthases / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014404:Tubulin / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D008767:Methylmercury Compounds; D014404:Tubulin; D014443:Tyrosine; D002268:Carboxypeptidases; C023212:tyrosyltubulin carboxypeptidase; D010453:Peptide Synthases; C023213:tyrosyltubulin ligase