Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, Lisboa 1649-003, Portugal.
Biochim Biophys Acta Gen Subj. 2019 Dec;1863(12):129255. doi: 10.1016/j.bbagen.2018.11.007. Epub 2018 Nov 14.
Mercury interaction with selenium in vivo has been recognized for >50 years. Several researchers attempted to use selenium to mitigate the detrimental effects of mercurial compounds but the results were controversial. Selenium pools in living organisms are quite low and the high affinity of mercury to bind selenols pointed out selenoproteins as possible targets of toxicity. Such was the case of the selenoenzyme thioredoxin reductase (TrxR) which is an integrant part of the thioredoxin system. Given the important role of this redox system for cellular functioning and the high affinity of mercury for TrxR's active site, this interaction can be key to understand the mechanism by which Hg causes cell death.
This review discusses the current state of knowledge concerning the interaction between mercury compounds and the thioredoxin system, its implications for the development of toxicity and the effects of selenium co-exposure.
The mechanism of toxicity of mercurials is a complex chain of events starting with inhibition of the selenoenzyme, TrxR. Selenium supplementation protects TrxR from the toxicity of inorganic forms of mercury (i.e., Hg(II)) to a certain extent, but not from methylmercury. When TrxR is inhibited, thioredoxin is reduced by alternative mechanisms involving glutathione and glutaredoxin and only when this pathway is hampered does cell death occur.
Understanding the molecular mechanism of mercury toxicity and the mechanisms of enzymatic compensation allows the design of mitigation strategies and, since TxrR and Trx exist in the plasma, puts forward the possibility for future use of changes in activity/expression of these enzymes as biomarkers of mercury toxicity, thus refining the risk assessment process.
汞与硒在体内的相互作用已被认识超过 50 年。一些研究人员试图利用硒来减轻汞化合物的有害影响，但结果存在争议。生物体中的硒库含量很低，而汞与硒醇结合的高亲和力指出硒蛋白可能是毒性的靶标。这种情况发生在硒酶硫氧还蛋白还原酶 (TrxR) 中，它是硫氧还蛋白系统的组成部分。鉴于该氧化还原系统对细胞功能的重要作用，以及汞对 TrxR 活性部位的高亲和力，这种相互作用可能是理解汞导致细胞死亡的机制的关键。
本文讨论了当前关于汞化合物与硫氧还蛋白系统相互作用的知识状况，及其对毒性发展的影响以及硒共暴露的影响。
汞化合物的毒性机制是一个复杂的事件链，始于抑制硒酶 TrxR。硒补充在一定程度上保护 TrxR 免受无机形式的汞（即 Hg(II)）的毒性，但不能免受甲基汞的毒性。当 TrxR 被抑制时，硫氧还蛋白通过涉及谷胱甘肽和谷氧还蛋白的替代机制被还原，只有当这条途径受阻时才会发生细胞死亡。
了解汞毒性的分子机制和酶补偿机制可以设计减轻策略，并且由于 TxrR 和 Trx 存在于血浆中，因此提出了将来将这些酶的活性/表达变化作为汞毒性生物标志物的可能性，从而完善了风险评估过程。
