Induction of glutamate-cysteine ligase (gamma-glutamylcysteine synthetase)in the brains of adult female mice subchronically exposed to methylmercury

Methylmercury (MeHg) is widely known for its potent neurotoxic properties. One proposed mechanism of action of MeHg relates to its high affinity for s ulfhydryl groups, especially those found on glutathione (GSH) and proteins. Previous studies have shown that acute MeHg exposure results in an increas e in the mRNA for the rate-limiting enzyme in GSH synthesis; glutamate-cyst eine ligase (GLCL) (also known as gamma-glutamylcysteine synthetase). In th is study, we evaluated the effects of subchronic (12-week) MeHg exposure at 0, 3 or 10 ppm in the drinking water on GSH levels, GLCL catalytic (GLCLC) and regulatory subunit mRNA and protein levels, and GLCL activity in brain , liver and kidney tissue of C57B1/6 female mice. Contrary to previous find ings in rats, there were no changes in GSH concentration in any of the tiss ues examined. However, there was an increase in GLCLC protein in the brain, which was accompanied by a 30% increase in GLCL activity. We conclude that up-regulation of GSH synthetic capacity in the brains of mice is a sensiti ve biomarker of subchronic MeHg exposure. (C) 1999 Published by Elsevier Sc ience Ireland Ltd. All rights reserved.