Marozkina Nadzeya, Gaston Benjamin
Herman Wells Center for Pediatric Research, Riley Hospital for Children, School of Medicine, Indiana University, Indianapolis, IN 46202, USA.
Indiana University, School of Medicine, 1044 W. Walnut Street, R4-474 Indianapolis, IN 46202, USA.
Antioxidants (Basel). 2020 Mar 10;9(3):225. doi: 10.3390/antiox9030225.
Long considered vital to antioxidant defenses, thiol chemistry has more recently been recognized to be of fundamental importance to cell signaling. S-nitrosothiols-such as S-nitrosoglutathione (GSNO)-and hydrogen sulfide (HS) are physiologic signaling thiols that are regulated enzymatically. Current evidence suggests that they modify target protein function primarily through post-translational modifications. GSNO is made by NOS and other metalloproteins; HS by metabolism of cysteine, homocysteine and cystathionine precursors. GSNO generally acts independently of NO generation and has a variety of gene regulatory, immune modulator, vascular, respiratory and neuronal effects. Some of this physiology is shared with HS, though the mechanisms differ. Recent evidence also suggests that molecules resulting from reactions between GSNO and HS, such as thionitrous acid (HSNO), could also have a role in physiology. Taken together, these data suggest important new potential targets for thiol-based drug development.
长期以来，硫醇化学一直被认为对抗氧化防御至关重要，最近人们认识到它对细胞信号传导也具有根本重要性。S-亚硝基硫醇（如S-亚硝基谷胱甘肽（GSNO））和硫化氢（HS）是通过酶促调节的生理性信号硫醇。目前的证据表明，它们主要通过翻译后修饰来改变靶蛋白功能。GSNO由一氧化氮合酶（NOS）和其他金属蛋白产生；HS由半胱氨酸、同型半胱氨酸和胱硫醚前体代谢产生。GSNO通常独立于NO的生成起作用，具有多种基因调节、免疫调节、血管、呼吸和神经效应。HS也有一些这样的生理作用，尽管机制不同。最近的证据还表明，GSNO和HS之间反应产生的分子，如硫亚硝酸（HSNO），也可能在生理过程中发挥作用。综合来看，这些数据表明基于硫醇的药物开发有重要的新潜在靶点。
