Differential oxidation of thioredoxin-1, thioredoxin-2, and glutathione by metal ions
Differential oxidation of thioredoxin-1, thioredoxin-2, and glutathione by metal ions
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DOI：
10.1016/j.freeradbiomed.2005.09.023
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发表时间：
2006-01-01
影响因子：
7.4
通讯作者：
Jones, DP
中科院分区：
文献类型：
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作者：
Hansen, JM;Zhang, H;Jones, DP
金属毒性通常包括活性氧（ROS）的产生和随后的氧化应激，但金属是否对主要硫醇抗氧化系统有不同的影响尚不清楚。在这里，我们研究了砷、镉、铯、铜、铁、汞、镍和锌对谷胱甘肽（GSH）、细胞质硫氧还蛋白-1 （Trx1）和线粒体硫氧还蛋白-2 （Trx2）氧化还原状态的影响。高效液相色谱法测定GSH/GSSG氧化还原状态，氧化还原Western blot法测定Trx1和Trx2氧化还原状态。铜、铁和镍对谷胱甘肽有明显的氧化作用，但对Trx1或Trx2的氧化作用相对较小。砷、镉和汞对谷胱甘肽的氧化作用不大，但对Trx1和Trx2的氧化作用明显。与细胞质Trx1 （20 ~ 40 mV）相比，砷、镉和汞对线粒体Trx2 （60 mV）的影响程度更大。凋亡信号调节激酶1 （Apoptosis signal- regulatory kinase 1, ASK1）可能通过两种不同的途径被激活，一种依赖于谷胱甘肽和glutaredoxin，另一种依赖于硫氧还蛋白而不依赖于谷胱甘肽。在氧化硫氧还毒素的金属中观察到ASK1的激活和细胞死亡，而在氧化GSH的金属中则没有观察到。这些发现表明，金属对主要的硫醇抗氧化系统有不同的氧化作用，细胞凋亡的激活可能与氧化硫氧还蛋白和激活ASK1的金属离子有关。主要硫醇抗氧化系统被金属离子氧化的差异表明，以GSH/GSSG和硫氧还毒素为代表的不同硫醇/二硫氧化还原对可能在凋亡和毒性信号通路中具有不同程度的控制。(c) 2005爱思唯尔公司版权所有。
Metal toxicity often includes the generation of reactive oxygen species (ROS) and subsequent oxidative stress, but whether metals have different effects on the major thiol antioxidant systems is unknown. Here, we examine the effects of arsenic, cadmium, cesium, copper, iron, mercury, nickel, and zinc on glutathione (GSH), cytoplasmic thioredoxin-1 (Trx1), and mitochondrial thioredoxin-2 (Trx2) redox states. GSH/GSSG redox states were determined by HPLC, and Trx1 and Trx2 redox states were determined by Redox Western blot methods. Copper, iron, and nickel showed significant oxidation of GSH but relatively little oxidation of either Trx1 or Trx2. Arsenic, cadmium, and mercury showed little oxidation of GSH but significantly oxidized both Trx1 and Trx2. The magnitude of effects of arsenic, cadmium, and mercury was greater for the mitochondrial Trx2 (> 60 mV) compared to the cytoplasmic Trx1 (20 to 40 mV). Apoptosis signal-regulating kinase 1 (ASK1) may be activated by two different pathways, one dependent upon GSH and glutaredoxin and the other independent of GSH and dependent upon thioredoxin. ASK1 activation and cell death were observed with metals that oxidized thioredoxins but not with metals that oxidized GSH. These findings show that metals have differential oxidative effects on the major thiol antioxidant systems and that activation of apoptosis may be associated with metal ions that oxidize thioredoxin and activate ASK1. The differential oxidation of the major thiol antioxidant systems by metal ions suggest that the distinct thiol/disulfide redox couples represented by GSH/GSSG and the thioredoxins may convey different levels of control in apoptotic and toxic signaling pathways. (c) 2005 Elsevier Inc. All rights reserved.