Nitric Oxide is a very well known gaseous second messenger molecule and vasorelaxant agent involved in a variety of signaling in the body such as neurotransmission, ion channel modulation, and inflammation modulation. However, it’s reversible covalent attachment to thiol groups of cysteine residues under nitrosative stress leading to aberrant protein S-nitrosylation (PSNO) has been reported in several pathological conditions in the body stemming from neurodegenerative diseases, cancer, cardiovascular system, and immune system disorders. In the cell, PSNOs are partly unstable and transit to a more stable disulfide state serving as an intermediate step towards disulfide formation thus eliciting the biological response. Scientists have identified several cellular thiol-dependent disulfide reductases that have the intrinsic capability to reverse the modification by reducing the stable disulfides formed in PSNOs and thereby rescue S-nitrosylation-induced altered proteins. The physiological roles of these major cellular ubiquitous S-denitrosylases and their probable implementations have not been fully explored. Gaining knowledge from current research and development this review provides a deeper insight into understanding the interplay and role of the major ubiquitous S-denitrosylases in maintaining cellular redox homeostasis. This review umbrellas the mechanism of Thioredoxin, TRP14, and Glutaredoxin systems and highlights their substrates specificities at different cellular conditions, physiological roles, and importance in diseased conditions that would allow researchers to investigate effective therapeutic interventions for nitrosative stress-related diseases and disorders.

一氧化氮是众所周知的气态第二信使分子和血管舒张剂，参与体内多种信号传导，例如神经传递、离子通道调节和炎症调节。然而，它在亚硝化应激下与半胱氨酸残基的硫醇基团可逆共价连接，导致异常的蛋白质S-亚硝基化(PSNO) 已在身体中由神经退行性疾病、癌症、心血管系统和免疫系统疾病引起的几种病理状况中得到报道。在细胞中，PSNOs 部分不稳定并转变为更稳定的二硫化物状态，作为形成二硫化物的中间步骤，从而引发生物反应。科学家们已经确定了几种细胞硫醇依赖性二硫化物还原酶，它们具有通过减少 PSNO 中形成的稳定二硫化物来逆转修饰的内在能力，从而拯救S-亚硝基化诱导的改变蛋白质。这些主要的细胞普遍存在的S的生理作用-denitrosylases 及其可能的实现尚未得到充分探索。从当前的研究和开发中获得知识，这篇综述提供了更深入的了解，了解主要普遍存在的S-脱亚硝基酶在维持细胞氧化还原稳态中的相互作用和作用。这篇综述概括了硫氧还蛋白、TRP14 和谷氧还蛋白系统的机制，并强调了它们在不同细胞条件下的底物特异性、生理作用和在疾病条件下的重要性，这将使研究人员能够研究与亚硝化应激相关的疾病和障碍的有效治疗干预措施。