The effects of chromium(VI) on the thioredoxin system: implications for redox regulation.
The effects of chromium(VI) on the thioredoxin system: implications for redox regulation.
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DOI：
10.1016/j.freeradbiomed.2012.03.013
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发表时间：
2012-05-15
影响因子：
7.4
通讯作者：
Myers, Charles R.
中科院分区：
文献类型：
--
作者：
Myers, Charles R.
关键词：
六价铬[Cr（VI）]化合物具有高度氧化还原活性，长期以来一直被认为是强效细胞毒素和致癌物。Cr（VI）的细胞内还原产生活性Cr中间体，其本身是强氧化剂，以及超氧化物、过氧化氢和羟基自由基。这些可能有助于氧化损伤和氧化还原敏感的转录因子的影响，已被报道。然而，启动这些信号变化的事件的识别一直是难以捉摸的。最近的研究表明，铬（VI）导致硫氧还蛋白还原酶（TrxR）的不可逆抑制以及硫氧还蛋白（Trx）和过氧化物氧还蛋白（Prx）的氧化。线粒体Trx 2/Prx 3比胞质Trx 1/Prx 1对Cr（VI）处理更敏感，尽管两个隔室都显示出较高剂量或较长时间处理的硫醇氧化。巯基氧化还原蛋白质组学表明，Trx 2，Prx 3和Trx 1是细胞中对Cr（VI）处理最敏感的蛋白质之一。因此，它们的氧化可能代表对蛋白质硫醇氧化还原控制和氧化还原信号传导的多个方面具有广泛影响的起始事件。本文综述了Cr（VI）对TrxR/Trx系统的影响，以及这些事件如何影响Cr（VI）暴露影响的一些下游氧化还原信号系统。讨论的一些信号传导事件包括凋亡信号调节激酶和MAP激酶（p38和JNK）的激活以及许多氧化还原敏感性转录因子（包括AP-1、NF-κB、p53和Nrf 2）的调节。
Hexavalent chromium [Cr(VI)] compounds are highly redox active and have long been recognized as potent cytotoxins and carcinogens. The intracellular reduction of Cr(VI) generates reactive Cr intermediates, which are themselves strong oxidants, as well as superoxide, hydrogen peroxide, and hydroxyl radical. These probably contribute to the oxidative damage and effects on redox-sensitive transcription factors that have been reported. However, the identification of events that initiate these signaling changes has been elusive. More recent studies show that Cr(VI) causes irreversible inhibition of thioredoxin reductase (TrxR) and oxidation of thioredoxin (Trx) and peroxiredoxin (Prx). Mitochondrial Trx2/Prx3 are more sensitive to Cr(VI) treatment than cytosolic Trx1/Prx1, although both compartments show thiol oxidation with higher doses or longer treatments. Thiol redox proteomics demonstrate that Trx2, Prx3, and Trx1 are among the most sensitive proteins in cells to Cr(VI) treatment. Their oxidation could therefore represent initiating events that have widespread implications for protein thiol redox control and for multiple aspects of redox signaling. This review summarizes the effects of Cr(VI) on the TrxR/Trx system and how these events could influence a number of downstream redox signaling systems that are influenced by Cr(VI) exposure. Some of the signaling events discussed include the activation of apoptosis signal regulating kinase and MAP kinases (p38 and JNK) and the modulation of a number of redox-sensitive transcription factors including AP-1, NF-κB, p53, and Nrf2.
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