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金属毒理学与金属硫蛋白中的细胞适应性

Cellular adaptation in metal toxicology and metallothionein.

作者信息

Cherian M G, Nordberg M

出版信息

Toxicology. 1983 Sep;28(1-2):1-15. doi: 10.1016/0300-483x(83)90101-4.

DOI:10.1016/0300-483x(83)90101-4
PMID:6314607
Abstract

The cellular adaptation to toxicity of metals is one of the important factors in the evaluation of health effects of increased exposure to metals. Two major types of cellular effects can be distinguished during divalent metal exposure. Some of the experimental evidences on the role of these processes in the cellular toxicity of metals are reviewed in this article. Both these cellular effects are somewhat specific to certain metals and involve two distinct types of protein binding. One of these processes can be considered as a nuclear process, involving binding of metals to nuclear proteins and also the formation of morphologically distinct inclusion bodies. A number of metals such as lead, bismuth, mercury, copper and aluminium are accumulated intranuclearly and bind with non-histone protein in the nuclei. In addition, morphologically distinct intranuclear inclusion bodies are formed in the kidneys of experimental animals and in humans on continuous exposure to lead or bismuth salts. Another cellular effect of divalent metals is a cytoplasmic process involving a specific metal binding protein, metallothionein. This is a unique metalloprotein containing 2 types of metal clusters and its synthesis is induced by both essential (Zn2+ and Cu2+) and non-essential (Cd2+ and Hg2+) metals. A hypothetical model for metal induced synthesis of metallothionein is postulated and is partly based on the recent immunohistochemical localization of metallothionein in the nucleus and cytoplasm of both hepatic and renal cells.

摘要

细胞对金属毒性的适应性是评估金属暴露增加对健康影响的重要因素之一。在二价金属暴露过程中可区分出两种主要类型的细胞效应。本文综述了关于这些过程在金属细胞毒性中作用的一些实验证据。这两种细胞效应在某种程度上对特定金属具有特异性,并且涉及两种不同类型的蛋白质结合。其中一个过程可被视为核过程,涉及金属与核蛋白的结合以及形态上不同的包涵体的形成。许多金属如铅、铋、汞、铜和铝在核内蓄积,并与核内的非组蛋白结合。此外,在实验动物和人类的肾脏中,持续接触铅盐或铋盐会形成形态上不同的核内包涵体。二价金属的另一种细胞效应是涉及一种特定金属结合蛋白——金属硫蛋白的细胞质过程。这是一种独特的金属蛋白,含有两种类型的金属簇,其合成由必需金属(锌离子和铜离子)和非必需金属(镉离子和汞离子)诱导。提出了一个金属诱导金属硫蛋白合成的假设模型,该模型部分基于最近金属硫蛋白在肝细胞和肾细胞的细胞核和细胞质中的免疫组织化学定位。

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