Induction of glutamate-cysteine ligase (γ-glutamylcysteine synthetase) in the brains of adult female mice subchronically exposed to methylmercury
Induction of glutamate-cysteine ligase (γ-glutamylcysteine synthetase) in the brains of adult female mice subchronically exposed to methylmercury
复制标题
DOI：
10.1016/s0378-4274(99)00133-2
复制
发表时间：
1999-10-29
影响因子：
3.5
通讯作者：
Kavanagh, TJ
中科院分区：
文献类型：
--
作者：
Thompson, SA;White, CC;Kavanagh, TJ
甲基汞(MeHg)因其强大的神经毒性而广为人知。甲基汞的一种作用机制与其对巯基的高亲和力有关，尤其是对谷胱甘肽和蛋白质上的那些。先前的研究表明，急性甲基汞暴露会导致谷胱甘肽合成限速酶-谷氨酸-半胱氨酸连接酶(GLCL)(也称为γ-谷氨酰半胱氨酸合成酶)的mRNA表达增加。在本研究中，我们评价了亚慢性(12周)暴露于饮用水中0、3和10ppm的甲基汞对C57B1/6雌性小鼠脑、肝和肾组织中GSH水平、GLCL催化(GLCLC)和调节亚基(GLCL)mRNA和蛋白水平以及GLCL活性的影响。与之前在大鼠身上的发现相反，在所检查的任何组织中，GSH浓度都没有变化。然而，脑组织中的GLCLC蛋白增加，并伴随着GLCL活性增加30%。我们的结论是，小鼠大脑中GSH合成能力的上调是亚慢性甲基汞暴露的敏感生物标志物。(C)1999由爱思唯尔科学爱尔兰有限公司出版。版权所有。
Methylmercury (MeHg) is widely known for its potent neurotoxic properties. One proposed mechanism of action of MeHg relates to its high affinity for sulfhydryl groups, especially those found on glutathione (GSH) and proteins. Previous studies have shown that acute MeHg exposure results in an increase in the mRNA for the rate-limiting enzyme in GSH synthesis; glutamate-cysteine ligase (GLCL) (also known as gamma-glutamylcysteine synthetase). In this 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 findings in rats, there were no changes in GSH concentration in any of the tissues 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 sensitive biomarker of subchronic MeHg exposure. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved.