Redox modifications of protein-thiols: Emerging roles in cell signaling
Redox modifications of protein-thiols: Emerging roles in cell signaling
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DOI：
10.1016/j.bcp.2005.10.044
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发表时间：
2006-02-28
影响因子：
5.8
通讯作者：
Rahman, I
中科院分区：
文献类型：
--
作者：
Biswas, S;Chida, AS;Rahman, I
谷氨酸代表哺乳动物细胞中主要的低分子量抗氧化剂氧化还原再循环硫醇，并在细胞防御氧化损伤中发挥核心作用。传统上，已知谷胱甘肽除了维持蛋白质处于还原状态之外，还为细胞提供还原环境。新出现的证据表明，谷胱甘肽的氧化还原状态可能需要通过可逆的二硫键形成的蛋白质功能的动态调节。蛋白质半胱氨酸和谷胱甘肽之间分子间和分子内二硫化物以及混合二硫化物的形成，即，S-谷胱甘肽化，现在已经与细胞外蛋白的稳定，保护蛋白质免受关键半胱氨酸残基的不可逆氧化，以及酶功能和转录的调节有关。氧化还原依赖性转录因子如核因子-κ B、p53和激活蛋白-1的DNA结合的调节已被认为是细胞可将氧化应激氧化还原信号传导转化为涉及细胞变化如增殖、分化和凋亡的多种基因的诱导表达的机制之一。然而，连接谷胱甘肽细胞氧化还原状态的各种信号蛋白的可逆氧化的分子机制仍然知之甚少。这篇评论讨论了蛋白质S-硫醇化，蛋白质S-亚硝化和蛋白质SH（形成次磺酸，亚磺酸和磺酸）在氧化还原信号在正常生理过程中和氧化应激下控制细胞过程的新兴概念。(c)2005年爱思唯尔公司All rights reserved.
Glutathione represents the major low molecular weight antioxidant redox recycling thiol in mammalian cells and plays a central role in the cellular defence against oxidative damage. Classically glutathione has been known to provide the cell with a reducing environment in addition to maintaining the proteins in a reduced state. Emerging evidences suggest that the glutathione redox status may entail dynamic regulation of protein function by reversible disulfide bond formation. The formation of inter- and intramolecular disulfides as well as mixed disuffides between protein cysteines and glutathione, i.e., S-glutathiolation, has now been associated with the stabilization of extracellular proteins, protection of proteins against irreversible oxidation of critical cysteine residues, and regulation of enzyme functions and transcription. Regulation of DNA binding of redox-dependent transcription factors such as nuclear factor-kappa B, p53, and activator protein-1, has been suggested as one of the mechanisms by which cells may transduce oxidative stress redox signaling into an inducible expression of a wide variety of genes implicated in cellular changes such as proliferation, differentiation, and apoptosis. However, the molecular mechanisms linking the glutathione cellular redox state to a reversible oxidation of various signaling proteins are still poorly understood. This commentary discusses the emerging concept of protein-S-thiolation, protein-S-nitrosation and protein-SH (formation of sulfenic, sulfinic and sulfonic acids) in redox signaling during normal physiology and under oxidative stress in controlling the cellular processes. (c) 2005 Elsevier Inc. All rights reserved.