Thioredoxin and thioredoxin reductase in relation to reversible S-nitrosylation.
Thioredoxin and thioredoxin reductase in relation to reversible S-nitrosylation.
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DOI：
10.1089/ars.2012.4716
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发表时间：
2013-01
影响因子：
6.6
通讯作者：
R. Sengupta;A. Holmgren
中科院分区：
文献类型：
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作者：
R. Sengupta;A. Holmgren
意义 一氧化氮 (NO) 调节多种细胞过程，包括血管舒张、神经传递以及抗菌和抗肿瘤活性。 S-亚硝基化形成 S-亚硝基硫醇 (RSNO) 是 NO 信号调节蛋白功能的重要特征。在哺乳动物细胞中，谷胱甘肽 (GSH)、S-亚硝基谷胱甘肽还原酶 (GSNOR) 和硫氧还蛋白 (Trx) 已被确定为主要的蛋白质脱亚硝基酶。最新进展二硫键形式的人胞浆/核 Trx1 可以在 Cys73 处亚硝基化，并转亚硝基化靶蛋白，包括 caspase 3。因此，与 GSH 类似，GSH 通过形成 S-亚硝基谷胱甘肽 (GSNO) 可以转亚硝基化蛋白质，Trx 可以根据其氧化态对蛋白质进行去亚硝基化或亚硝基化。关键问题在这篇综述中，我们讨论了 RSNO 和 S-亚硝基蛋白的可逆 S-亚硝基化和 Trx 介导的细胞稳态对细胞过程的调节。未来方向 RSNO 的体内功能及其药理学用途尚未得到充分研究。进一步研究 Trx 系统与生物学相关 RSNO 相关的作用、其功能以及去亚硝基化机制将有助于药物和疗法的开发。抗氧化剂。氧化还原信号。 18、259-269。
SIGNIFICANCE Nitric oxide (NO) regulates a diverse range of cellular processes, including vasodilation, neurotransmission, and antimicrobial and anti-tumor activities. S-nitrosylation with the formation of S-nitrosothiols (RSNOs) is an important feature of NO signaling regulating protein function. In mammalian cells, glutathione (GSH), S-nitrosoglutathione reductase (GSNOR), and thioredoxin (Trx) have been identified as the major protein denitrosylases. RECENT ADVANCES Human cytosolic/nuclear Trx1 in the disulfide form can be nitrosylated at Cys73 and transnitrosylate target proteins, including caspase 3. Thus, similar to GSH, which by forming S-nitrosoglutathione (GSNO) can transnitrosylate proteins, Trx can either denitrosylate or nitrosylate proteins depending on its oxidation state. CRITICAL ISSUES In this review, we discuss the regulation of cellular processes by reversible S-nitrosylation and Trx-mediated cellular homeostasis of RSNOs and S-nitrosoproteins. FUTURE DIRECTIONS Functions of RSNOs in vivo and their pharmacological uses have not yet been fully studied. Further investigations on the role of Trx systems in relation to biologically relevant RSNOs, their functions, and the mechanisms of denitrosylation will facilitate the development of drugs and therapies. Antioxid. Redox Signal. 18, 259-269.