Aschner M, Mullaney K J, Wagoner D, Lash L H, Kimelberg H K
Department of Pharmacology and Toxicology, Albany Medical College, NY.
Brain Res. 1994 Nov 21;664(1-2):133-40. doi: 10.1016/0006-8993(94)91963-1.
Mercuric chloride (MC) and methylmercury (MeHg) were found to increase amino acid release from astrocytes. This suggests interaction with sulfhydryl (-SH) groups which are controlled by glutathione [GSH] levels. In the present study, we evaluated the effects of alterations in intracellular glutathione concentrations [GSH]i on the outcome of MC and MeHg treatment. [GSH]i were increased in a time-dependent fashion by incubating the astrocytes with 1 mM L-2-oxothiazolidine-4-carboxylic acid (OTC), a cysteine precursor. OTC attenuated the release of [2,3-3H]D-aspartic acid from astrocytes exposed to MC- (5 microM) and MeHg-(10 microM). MeHg-induced [3H]D-taurine release was also reduced by pretreatment of astrocytes with OTC. Treatment with BSO (50 microM) decreased [GSH]i in astrocytes, and increased [2,3-3H]D-aspartate release from MC- and MeHg-treated astrocytes, and [3H]D-taurine release from MeHg-treated cells. Neither OTC nor BSO when added to cultures in the absence of MC or MeHg had an effect on amino acid release by astrocytes. The current study underscores both the sensitivity of astrocytes to mercurials in terms of amino acid release and the relationship of these effects of astrocytic [GSH]i.
已发现氯化汞（MC）和甲基汞（MeHg）可增加星形胶质细胞释放氨基酸。这表明其与受谷胱甘肽[GSH]水平控制的巯基（-SH）基团相互作用。在本研究中，我们评估了细胞内谷胱甘肽浓度[GSH]i的改变对MC和MeHg处理结果的影响。通过用1 mM L-2-氧代噻唑烷-4-羧酸（OTC，一种半胱氨酸前体）孵育星形胶质细胞，[GSH]i以时间依赖性方式增加。OTC减弱了暴露于MC（5 microM）和MeHg（10 microM）的星形胶质细胞中[2,3-3H]D-天冬氨酸的释放。用OTC预处理星形胶质细胞也可减少MeHg诱导的[3H]D-牛磺酸释放。用BSO（50 microM）处理可降低星形胶质细胞中的[GSH]i，并增加MC和MeHg处理的星形胶质细胞中[2,3-3H]D-天冬氨酸的释放，以及MeHg处理细胞中[3H]D-牛磺酸的释放。在无MC或MeHg的情况下添加到培养物中的OTC和BSO均对星形胶质细胞释放氨基酸无影响。当前研究强调了星形胶质细胞在氨基酸释放方面对汞化合物的敏感性以及星形胶质细胞[GSH]i这些效应之间的关系。
