Redox Signaling and Oxidative Stress Research Group, Cell Stress and Survival Unit, Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Society Research Center, Copenhagen, Denmark.
Redox Signaling and Oxidative Stress Research Group, Cell Stress and Survival Unit, Center for Autophagy, Recycling and Disease (CARD), Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Biology, University of Rome Tor Vergata, Rome, Italy.
Free Radic Biol Med. 2017 Sep;110:19-30. doi: 10.1016/j.freeradbiomed.2017.05.014. Epub 2017 May 19.
S-nitrosylation is a major redox posttranslational modification involved in cell signaling. The steady state concentration of S-nitrosylated proteins depends on the balance between the relative ability to generate nitric oxide (NO) via NO synthase and to reduce nitrosothiols by denitrosylases. Numerous works have been published in last decades regarding the role of NO and S-nitrosylation in the regulation of protein structure and function, and in driving cellular activities in vertebrates. Notwithstanding an increasing number of observations indicates that impairment of denitrosylation equally affects cellular homeostasis, there is still no report providing comprehensive knowledge on the impact that denitrosylation has on maintaining correct physiological processes and organ activities. Among denitrosylases, S-nitrosoglutathione reductase (GSNOR) represents the prototype enzyme to disclose how denitrosylation plays a crucial role in tuning NO-bioactivity and how much it deeply impacts on cell homeostasis and human patho-physiology. In this review we attempt to illustrate the history of GSNOR discovery and provide the evidence so far reported in support of GSNOR implications in development and human disease.
S-亚硝基化是一种主要的氧化还原翻译后修饰，参与细胞信号转导。S-亚硝基化蛋白质的稳态浓度取决于通过一氧化氮合酶生成一氧化氮 (NO) 的相对能力和通过去亚硝酰酶还原亚硝硫醇的相对能力之间的平衡。在过去几十年中，已经发表了许多关于 NO 和 S-亚硝基化在调节蛋白质结构和功能以及驱动脊椎动物细胞活动中的作用的研究。尽管越来越多的观察结果表明，去亚硝酰化的损伤同样会影响细胞内环境的稳定，但仍没有报道全面阐述去亚硝酰化对维持正确的生理过程和器官活动的影响。在去亚硝酰酶中，S-亚硝基谷胱甘肽还原酶 (GSNOR) 是揭示去亚硝酰化如何在调节 NO 生物活性中发挥关键作用以及对细胞内环境稳定和人类病理生理学产生多大影响的典型酶。在这篇综述中，我们试图阐明 GSNOR 发现的历史，并提供迄今为止报道的支持 GSNOR 在发育和人类疾病中的作用的证据。
