INHIBITION OF AMINO-ACID TRANSPORT AND PROTEIN-SYNTHESIS BY HGCL2 AND METHYLMERCURY IN ASTROCYTES - SELECTIVITY AND REVERSIBILITY
INHIBITION OF AMINO-ACID TRANSPORT AND PROTEIN-SYNTHESIS BY HGCL2 AND METHYLMERCURY IN ASTROCYTES - SELECTIVITY AND REVERSIBILITY
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DOI：
10.1111/j.1471-4159.1989.tb07419.x
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发表时间：
1989-10-01
影响因子：
4.7
通讯作者：
KRISTT, DA
中科院分区：
文献类型：
--
作者：
BROOKES, N;KRISTT, DA
先前报道的亚微摩尔浓度的HgCl2可逆地抑制星形胶质细胞对谷氨酸的摄取，而不影响2-脱氧葡萄糖的摄取，这表明元素汞蒸气在大脑中被氧化为汞，可能通过谷氨酸兴奋毒性的中介而导致神经退行性改变。在这里，通过测量对其他氨基酸转运体和蛋白质合成的抑制作为HgCl2浓度的函数来进一步探索选择性。在相同的条件下，比较了MeHgCl的性质，并对一些功能的形态相关性进行了检验。HgCl2对氨基酸转运的抑制是选择性的，而MeHgCl2是非选择性的。HgCl2对体系A摄取α-氨基异丁酸、L变异体摄取α-氨基异丁酸或犬尿氨酸以及摄取γ-氨基丁酸的50%抑制浓度均比摄取谷氨酸大2~4倍。抑制谷氨酸转运的亚微摩尔浓度的HgCl2也抑制蛋白质合成，但以一种快速可逆的方式，仅引起离散的超微结构变化(异染色质、溶酶体数量增加和细胞表面复杂性增加)。相反，MeHgCl对蛋白质合成的抑制(1-h)是不可逆的，只有当浓度高于引起“泡”样肿胀形式的大体形态变化的浓度时，才会变得明显。这些结果支持汞蒸气神经毒性的兴奋性毒性中介作用，并揭示了HgCl2和MeHgCl2对星形胶质细胞的影响之间的鲜明对比。
The previously reported observation that submicromolar concentrations of HgCl2 inhibit glutamate uptake reversibly in astrocytes, without effect on 2-deoxyglucose uptake, suggested that elemental mercury vapor, which is oxidized to mercuric mercury in the brain, might cause neurodegenerative change through the mediation of glutamate excitotoxicity. Here, selectivity is explored further by measuring the inhibition of other amino acid transporters and protein synthesis as a function of HgCl2 concentration. The properties of MeHgCl were compared under identical conditions, and some morphological correlates of function were examined. Inhibition of amino acid transport by HgCl2 was selective, whereas MeHgCl was nonselective. The 50% inhibitory concentrations of HgCl2 for uptake of .alpha.-aminoisobutyric acid by system A, uptake of .alpha.-aminoisobutyric acid or kynurenine by a system L variant, and uptake of .gamma.-aminobutyric acid were all two- to fourfold greater than that for uptake of glutamate. The submicromolar concentrations of HgCl2 that inhibited glutamate transport also inhibited protein synthesis, but in a rapidly reversible fashion, and elicited only discrete ultrastructural changes (heterochromatin, increased numbers of lysosomal bodies, and increased complexity of cell surface). In contrast, inhibition of protein synthesis by MeHgCl was acutely (1-h) irreversible and became marked only at concentrations higher than those that elicited gross morphologic change in the form of "bleb"-like swellings. The results lend support to the proposed excitotoxic mediation of mercury vapor neurotoxicity and reveal a sharp contrast between the effects of HgCl2 and MeHgCl on astrocytes.