Kimura Hideo
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Sanyo-Onoda, Japan.
Br J Pharmacol. 2020 Nov;177(22):5031-5045. doi: 10.1111/bph.15246. Epub 2020 Sep 20.
Hydrogen sulfide (H S) together with polysulfides (H S , n > 2) are signalling molecules like NO with various physiological roles including regulation of neuronal transmission, vascular tone, inflammation and oxygen sensing. H S and H S diffuse to the target proteins for S-sulfurating their cysteine residues that induces the conformational changes to alter the activity. On the other hand, 3-mercaptopyruvate sulfurtransferase transfers sulfur from a substrate 3-mercaptopyruvate to the cysteine residues of acceptor proteins. A similar mechanism has also been identified in S-nitrosylation. S-sulfuration and S-nitrosylation by enzymes proceed only inside the cell, while reactions induced by H S, H S and NO even extend to the surrounding cells. Disturbance of signalling by these molecules as well as S-sulfuration and S-nitrosylation causes many nervous system diseases. This review focuses on the signalling by H S and H S with S-sulfuration comparing to that of NO with S-nitrosylation and discusses on their roles in physiology and pathophysiology.
硫化氢(H₂S)与多硫化物(H₂Sₙ,n > 2)一样,都是信号分子,类似于一氧化氮(NO),具有多种生理作用,包括调节神经传递、血管张力、炎症和氧感应。H₂S和H₂Sₙ扩散至靶蛋白,对其半胱氨酸残基进行S-硫化,从而诱导构象变化以改变活性。另一方面,3-巯基丙酮酸硫转移酶将硫从底物3-巯基丙酮酸转移至受体蛋白的半胱氨酸残基。在S-亚硝基化过程中也发现了类似机制。酶介导的S-硫化和S-亚硝基化仅在细胞内进行,而H₂S、H₂Sₙ和NO诱导的反应甚至会扩展至周围细胞。这些分子以及S-硫化和S-亚硝基化引起的信号传导紊乱会导致许多神经系统疾病。本综述重点关注H₂S和H₂Sₙ的S-硫化信号传导,并与NO的S-亚硝基化信号传导进行比较,同时讨论它们在生理和病理生理中的作用。