BILIARY-SECRETION OF GLUTATHIONE AND OF GLUTATHIONE METAL-COMPLEXES
BILIARY-SECRETION OF GLUTATHIONE AND OF GLUTATHIONE METAL-COMPLEXES
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DOI：
10.1016/0272-0590(85)90165-4
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发表时间：
1985-01-01
期刊：
影响因子：
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通讯作者：
CLARKSON, TW
中科院分区：
文献类型：
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作者：
BALLATORI, N;CLARKSON, TW
谷胱甘肽和谷胱甘肽金属络合物的胆汁分泌。张晓华，陈晓华(1985).北京：北京.APPL毒素。5,816-831。由于胆汁是许多金属的主要清除途径，因此大量的研究针对内源性和外源性金属在肝胆中的转运进行了研究。尽管已经取得了一些进展，但我们仍然对肝细胞摄取金属、细胞内金属转运和代谢以及金属转运到胆汁中的基本机制知之甚少。我们最近的研究集中在汞在肝胆中转运的最后一步，即金属从肝细胞分泌到胆汁中。哺乳期大鼠胆汁中甲基汞和无机汞的分泌率很低，断奶后不久迅速上升到成年率。这些变化与还原型谷胱甘肽(GSH)胆汁分泌的发育变化相似。当GSH分泌到胆汁中完全被抑制时，在不改变肝脏GSH或汞水平的情况下，汞的分泌也完全被阻断。汞的分泌与GSH分泌的个体和性别的差异是平行的。同时，汞的分泌与胆汁流量、胆汁和肝细胞之间的硫醇和汞浓度梯度以及胆汁和血浆之间的浓度梯度无关。因此，我们的结果表明汞的分泌和谷胱甘肽的分泌之间存在密切的耦合。这些活体发现，以及其他人在从肝细胞小管膜分离的囊泡中进行的体外研究，表明了GSH的载体介导的运输系统，但该运输系统与汞分泌的联系的性质尚未完全确定。我们的数据和文献中的数据与至少两个步骤参与了汞从肝细胞向胆汁的移动-在肝细胞中形成汞-谷胱甘肽复合体，然后通过与GSH分泌密切相关的过程分泌该复合体。将GSH确定为组织和体液之间金属运输的内源性络合剂，现在可以设计治疗策略，旨在利用这种运输工具通过生理排泄途径实现金属的清除。本文讨论了GSH在金属的肝胆转运中的作用。为此，简要回顾了目前对肝脏谷胱甘肽代谢和转运的了解。
Biliary Secretion of Glutathione and of Glutathione-Metal Complexes. Ballatori, N., and Clarkson, T. W. (1985).Fundam. Appl. Toxicol.5, 816-831. As bile is the main route of elimination of many metals, a large number of studies have been directed toward the characterization of the hepatobiliary transport of both endogenous and exogenous metals. Although some progress has been made, we still know little of the basic mechanisms involved in the hepatocellular uptake of metals, in their intracellular translocation and metabolism, or in their transport into bile. Our recent studies have focused on the last step in the hepatobiliary transport of mercury, namely, the secretion of the metal from liver cells into bile. The rate of secretion of methyl and inorganic mercury into bile was low in suckling rats and rapidly increased to adult rates soon after weaning. These changes closely followed similar developmental changes in the biliary secretion of reduced glutathione (GSH). When GSH secretion into bile was completely inhibited, without changing hepatic levels of GSH or mercury, mercury secretion was also completely blocked. Mercury secretion paralleled individual and sex-related differences in GSH secretion. At the same time, the secretion of mercury was independent of bile flow, of the thiol and mercury concentration gradients between bile and liver cells, and of those between bile and plasma. Our results, therefore, indicate a close coupling between the secretion of mercury and that of GSH. Thesein vivofindings, along within vitrostudies by others in vesicles isolated from the canalicular membrane of the liver cell, indicate a carrier-mediated transport system for GSH, but the nature of the linkage of this transport system with mercury secretion is not yet fully established. Our data and those in the literature are consistent with the involvement of at least two steps in the movement of mercury from liver cells to bile—the formation of a mercury-glutathione complex in the liver cell, followed by the secretion of this complex through a process closely linked to GSH secretion. The identification of GSH as an endogenous complexing agent in the transport of metals between tissues and body fluids now permits the design of therapeutic strategies aimed at exploiting this transport vehicle to effect the removal of metals via physiological routes of excretion. The present discussion considers the role of GSH in the hepatobiliary transport of metals. In doing so, a brief review is given of current understanding of hepatic GSH metabolism and transport.