Department of Chemistry, Johns Hopkins University, Baltimore, MD, 21218, USA.
William Harvey Research Institute, Barts & The London School of Medicine, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
Free Radic Biol Med. 2022 Aug 1;188:459-467. doi: 10.1016/j.freeradbiomed.2022.06.245. Epub 2022 Jul 6.
S-Nitrosothiol (RS-NO) generation/levels have been implicated as being important to numerous physiological and pathophysiological processes. As such, the mechanism(s) of their generation and degradation are important factors in determining their biological activity. Along with the effects on the activity of thiol proteins, RS-NOs have also been reported to be reservoirs or storage forms of nitric oxide (NO). That is, it is hypothesized that NO can be released from RS-NO at opportune times to, for example, regulate vascular tone. However, to date there are few established mechanisms that can account for facile NO release from RS-NO. Recent discovery of the biological formation and prevalence of hydropersulfides (RSSH) and their subsequent reaction with RS-NO species provides a possible route for NO release from RS-NO. Herein, it is found that RSSH is capable of reacting with RS-NO to liberate NO and that the analogous reaction using RSH is not nearly as proficient in generating NO. Moreover, computational results support the prevalence of this reaction over other possible competing processes. Finally, results of biological studies of NO-mediated vasorelaxation are consistent with the idea that RS-NO species can be degraded by RSSH to release NO.
S-亚硝基硫醇 (RS-NO) 的生成/水平被认为对许多生理和病理生理过程很重要。因此，它们的生成和降解机制是决定其生物活性的重要因素。除了对硫醇蛋白活性的影响外，RS-NO 也被报道为一氧化氮 (NO) 的储库或储存形式。也就是说，据推测，NO 可以从 RS-NO 中适时释放出来，例如调节血管张力。然而，迄今为止，很少有确定的机制可以解释 RS-NO 中易于发生的 NO 释放。最近发现生物形成和普遍存在的水合过硫化物 (RSSH) 及其随后与 RS-NO 物种的反应为从 RS-NO 释放 NO 提供了一种可能的途径。在这里，发现 RSSH 能够与 RS-NO 反应释放 NO，而使用 RSH 的类似反应生成 NO 的效率则要低得多。此外，计算结果支持该反应比其他可能的竞争过程更为普遍。最后，NO 介导的血管舒张的生物学研究结果与 RS-NO 物种可以被 RSSH 降解以释放 NO 的观点一致。
