Molecular interactions with mercury in the kidney.
Molecular interactions with mercury in the kidney.
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DOI：
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发表时间：
2000-03
影响因子：
21.1
通讯作者：
Rudolfs K. Zalups
中科院分区：
文献类型：
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作者：
Rudolfs K. Zalups
汞在重金属中是独一无二的，因为它可以以几种物理和化学形式存在，包括元素汞，它在室温下是液体。所有形式的汞对许多器官都有毒性作用，特别是对肾脏。在肾脏内，近端小管的直肠部是肾单位中最容易受到汞毒性影响的部分。汞离子和汞离子在肾脏中的生物和毒理活性在很大程度上可以由靶细胞内和周围的关键亲核位点上发生的分子相互作用来定义。由于汞和硫之间的高成键亲和力，人们对汞离子与蛋白质、多肽和氨基酸的硫醇基团(S)之间的相互作用特别感兴趣。白蛋白、金属硫蛋白、谷胱甘肽和半胱氨酸分子中的巯基与分子间的相互作用参与了汞离子近端肾小管摄取、蓄积、转运和毒性的机制。此外，肾脏中靶细胞对汞损伤效应的敏感性被与几个含有硫醇的分子有关的许多细胞内和细胞外因子所改变。这些因素正是目前所采用的大多数治疗策略的理论基础。本文综述了目前有关汞与各种硫醇分子之间的分子相互作用的最新知识，这些相互作用涉及肾细胞对汞的摄取、积累、消除和毒性的机制。
Mercury is unique among the heavy metals in that it can exist in several physical and chemical forms, including elemental mercury, which is a liquid at room temperature. All forms of mercury have toxic effects in a number of organs, especially in the kidneys. Within the kidney, the pars recta of the proximal tubule is the most vulnerable segment of the nephron to the toxic effects of mercury. The biological and toxicological activity of mercurous and mercuric ions in the kidney can be defined largely by the molecular interactions that occur at critical nucleophilic sites in and around target cells. Because of the high bonding affinity between mercury and sulfur, there is particular interest in the interactions that occur between mercuric ions and the thiol group(s) of proteins, peptides and amino acids. Molecular interactions with sulfhydryl groups in molecules of albumin, metallothionein, glutathione, and cysteine have been implicated in mechanisms involved in the proximal tubular uptake, accumulation, transport, and toxicity of mercuric ions. In addition, the susceptibility of target cells in the kidneys to the injurious effects of mercury is modified by a number of intracellular and extracellular factors relating to several thiol-containing molecules. These very factors are the theoretical basis for most of the currently employed therapeutic strategies. This review provides an update on the current body of knowledge regarding the molecular interactions that occur between mercury and various thiol-containing molecules with respect to the mechanisms involved in the renal cellular uptake, accumulation, elimination, and toxicity of mercury.