Wolhuter Kathryn, Eaton Philip
King's College London, Cardiovascular Division, The British Heart Foundation Centre of Excellence, The Rayne Institute, St Thomas' Hospital, London SE1 7EH, UK.
King's College London, Cardiovascular Division, The British Heart Foundation Centre of Excellence, The Rayne Institute, St Thomas' Hospital, London SE1 7EH, UK.
Free Radic Biol Med. 2017 Aug;109:156-166. doi: 10.1016/j.freeradbiomed.2017.02.013. Epub 2017 Feb 9.
Over the last 25 years protein S-nitrosylation, also known more correctly as S-nitrosation, has been progressively implicated in virtually every nitric oxide-regulated process within the cardiovascular system. The current, widely-held paradigm is that S-nitrosylation plays an equivalent role as phosphorylation, providing a stable and controllable post-translational modification that directly regulates end-effector target proteins to elicit biological responses. However, this concept largely ignores the intrinsic instability of the nitrosothiol bond, which rapidly reacts with typically abundant thiol-containing molecules to generate more stable disulfide bonds. These protein disulfides, formed via a nitrosothiol intermediate redox state, are rationally anticipated to be the predominant end-effector modification that mediates functional alterations when cells encounter nitrosative stimuli. In this review we present evidence and explain our reasoning for arriving at this conclusion that may be controversial to some researchers in the field.
在过去25年里,蛋白质S-亚硝基化,更准确地说应是S-亚硝化作用,已逐渐被认为几乎涉及心血管系统内每一个一氧化氮调节的过程。当前广泛持有的范式是,S-亚硝基化发挥着与磷酸化同等的作用,提供一种稳定且可控的翻译后修饰,直接调节终效应靶蛋白以引发生物学反应。然而,这一概念很大程度上忽略了亚硝基硫醇键的内在不稳定性,该键会迅速与通常大量存在的含硫醇分子反应,生成更稳定的二硫键。这些通过亚硝基硫醇中间氧化还原状态形成的蛋白质二硫键,合理推测应是细胞遇到亚硝化刺激时介导功能改变的主要终效应修饰。在本综述中,我们展示了证据并解释了得出这一结论的推理过程,这一结论可能会引起该领域一些研究人员的争议。