Chakraborty Surupa, Sircar Esha, Bhattacharyya Camelia, Choudhuri Ankita, Mishra Akansha, Dutta Sreejita, Bhatta Sneha, Sachin Kumar, Sengupta Rajib
Amity Institute of Biotechnology Kolkata, Amity University Kolkata, Action Area II, Rajarhat, Newtown, Kolkata 700135, West Bengal, India.
Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Roorkee 247667, Uttarakhand, India.
Antioxidants (Basel). 2022 Sep 28;11(10):1921. doi: 10.3390/antiox11101921.
S-nitrosylation of proteins occurs as a consequence of the derivatization of cysteine thiols with nitric oxide (NO) and is often associated with diseases and protein malfunction. Aberrant S-nitrosylation, in addition to other genetic and epigenetic factors, has gained rapid importance as a prime cause of various metabolic, respiratory, and cardiac disorders, with a major emphasis on cancer and neurodegeneration. The S-nitrosoproteome, a term used to collectively refer to the diverse and dynamic repertoire of S-nitrosylated proteins, is relatively less explored in the field of redox biochemistry, in contrast to other covalently modified versions of the same set of proteins. Advancing research is gradually unveiling the enormous clinical importance of S-nitrosylation in the etiology of diseases and is opening up new avenues of prompt diagnosis that harness this phenomenon. Ever since the discovery of the two robust and highly conserved S-nitrosoglutathione reductase and thioredoxin systems as candidate denitrosylases, years of rampant speculation centered around the identification of specific substrates and other candidate denitrosylases, subcellular localization of both substrates and denitrosylases, the position of susceptible thiols, mechanisms of S-denitrosylation under basal and stimulus-dependent conditions, impact on protein conformation and function, and extrapolating these findings towards the understanding of diseases, aging and the development of novel therapeutic strategies. However, newer insights in the ever-expanding field of redox biology reveal distinct gaps in exploring the crucial crosstalk between the redoxins/major denitrosylase systems. Clarifying the importance of the functional overlap of the glutaredoxin, glutathione, and thioredoxin systems and examining their complementary functions as denitrosylases and antioxidant enzymatic defense systems are essential prerequisites for devising a rationale that could aid in predicting the extent of cell survival under high oxidative/nitrosative stress while taking into account the existence of the alternative and compensatory regulatory mechanisms. This review thus attempts to highlight major gaps in our understanding of the robust cellular redox regulation system, which is upheld by the concerted efforts of various denitrosylases and antioxidants.
蛋白质的S-亚硝基化是由于一氧化氮（NO）与半胱氨酸硫醇发生衍生化作用而产生的，并且常常与疾病和蛋白质功能异常相关。除了其他遗传和表观遗传因素外，异常的S-亚硝基化作为各种代谢、呼吸和心脏疾病的主要原因，已迅速变得重要起来，其中重点是癌症和神经退行性变。S-亚硝基蛋白质组是一个用于统称多样化且动态变化的S-亚硝基化蛋白质库的术语，与同一组蛋白质的其他共价修饰形式相比，在氧化还原生物化学领域中对其研究相对较少。不断推进的研究正逐渐揭示S-亚硝基化在疾病病因学中的巨大临床重要性，并开辟利用这一现象进行快速诊断的新途径。自从发现两种强大且高度保守的S-亚硝基谷胱甘肽还原酶和硫氧还蛋白系统作为候选去亚硝基化酶以来，多年来围绕特定底物和其他候选去亚硝基化酶的鉴定、底物和去亚硝基化酶的亚细胞定位、易感硫醇的位置、基础和刺激依赖性条件下S-去亚硝基化的机制、对蛋白质构象和功能的影响以及将这些发现外推以理解疾病、衰老和开发新型治疗策略等方面进行了大量的推测。然而，在不断扩展的氧化还原生物学领域中的新见解揭示了在探索氧化还原蛋白/主要去亚硝基化酶系统之间关键的相互作用方面存在明显差距。阐明谷氧还蛋白、谷胱甘肽和硫氧还蛋白系统功能重叠的重要性，并研究它们作为去亚硝基化酶和抗氧化酶防御系统的互补功能，是设计一种有助于预测在高氧化/亚硝化应激下细胞存活程度的理论基础的必要前提，同时要考虑到替代和补偿性调节机制的存在。因此，本综述试图突出我们在理解由各种去亚硝基化酶和抗氧化剂共同作用维持的强大细胞氧化还原调节系统方面的主要差距。
