Department of Chemistry and Pharmacy, University of Erlangen-Nürnberg, 91058 Erlangen, Germany.
J Am Chem Soc. 2012 Jul 25;134(29):12016-27. doi: 10.1021/ja3009693. Epub 2012 Jul 17.
Dihydrogen sulfide recently emerged as a biological signaling molecule with important physiological roles and significant pharmacological potential. Chemically plausible explanations for its mechanisms of action have remained elusive, however. Here, we report that H(2)S reacts with S-nitrosothiols to form thionitrous acid (HSNO), the smallest S-nitrosothiol. These results demonstrate that, at the cellular level, HSNO can be metabolized to afford NO(+), NO, and NO(-) species, all of which have distinct physiological consequences of their own. We further show that HSNO can freely diffuse through membranes, facilitating transnitrosation of proteins such as hemoglobin. The data presented in this study explain some of the physiological effects ascribed to H(2)S, but, more broadly, introduce a new signaling molecule, HSNO, and suggest that it may play a key role in cellular redox regulation.
硫化氢最近作为一种具有重要生理作用和显著药理学潜力的生物信号分子而出现。然而，其作用机制的化学解释仍然难以捉摸。在这里，我们报告 H(2)S 与 S-亚硝基硫醇反应形成亚硝硫醇（HSNO），这是最小的 S-亚硝基硫醇。这些结果表明，在细胞水平上，HSNO 可以代谢生成 NO(+)、NO 和 NO(-)，所有这些物质都有其自身独特的生理后果。我们进一步表明，HSNO 可以自由扩散穿过膜，促进血红蛋白等蛋白质的转亚硝基化。本研究中提出的实验数据解释了一些归因于 H(2)S 的生理效应，但更广泛地说，引入了一种新的信号分子 HSNO，并表明它可能在细胞氧化还原调节中发挥关键作用。
