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哺乳动物体内无机汞与硒拮抗作用的结构基础

Structural basis of the antagonism between inorganic mercury and selenium in mammals.

作者信息

Gailer J, George G N, Pickering I J, Madden S, Prince R C, Yu E Y, Denton M B, Younis H S, Aposhian H V

机构信息

Department of Molecular and Cellular Biology, The University of Arizona, Life Sciences South Building, Tucson, Arizona 85721, USA.

出版信息

Chem Res Toxicol. 2000 Nov;13(11):1135-42. doi: 10.1021/tx000050h.

DOI:10.1021/tx000050h
PMID:11087435
Abstract

Mercuric chloride toxicity in mammals can be overcome by co-administration of sodium selenite. We report a study of the mutual detoxification product in rabbit plasma, and of a Hg-Se-S-containing species synthesized by addition of equimolar mercuric chloride and sodium selenite to aqueous, buffered glutathione. Chromatographic purification of this Hg-Se-S species and subsequent structural analysis by Se and Hg extended X-ray absorption fine structure (EXAFS) spectroscopy revealed the presence of four-coordinate Se and Hg entities separated by 2.61 A. Hg and Se near-edge X-ray absorption spectroscopy of erythrocytes, plasma, and bile of rabbits that had been injected with solutions of sodium selenite and mercuric chloride showed that Hg and Se in plasma samples exhibited X-ray absorption spectra that were essentially identical to those of the synthetic Hg-Se-S species. Thus, the molecular detoxification product of sodium selenite and mercuric chloride in rabbits exhibits similarities to the synthetic Hg-Se-S species. The underlying molecular mechanism for the formation of the Hg-Se-S species is discussed.

摘要

哺乳动物中氯化汞毒性可通过同时给予亚硒酸钠来克服。我们报告了一项关于兔血浆中相互解毒产物的研究,以及通过向含缓冲剂的谷胱甘肽水溶液中添加等摩尔的氯化汞和亚硒酸钠合成的一种含汞 - 硒 - 硫物种的研究。对该汞 - 硒 - 硫物种进行色谱纯化,并随后通过硒和汞扩展X射线吸收精细结构(EXAFS)光谱进行结构分析,结果显示存在由2.61埃分隔的四配位硒和汞实体。对注射了亚硒酸钠和氯化汞溶液的兔子的红细胞、血浆和胆汁进行汞和硒近边X射线吸收光谱分析表明,血浆样品中的汞和硒呈现出与合成汞 - 硒 - 硫物种基本相同的X射线吸收光谱。因此,兔子中亚硒酸钠和氯化汞的分子解毒产物与合成汞 - 硒 - 硫物种具有相似性。文中讨论了汞 - 硒 - 硫物种形成的潜在分子机制。

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