Amity Institute of Biotechnology Kolkata, Amity University Kolkata, Action Area II, Kadampukur Village, Rajarhat, Newtown, Kolkata, West Bengal 700135, India.
Amity Institute of Biotechnology Kolkata, Amity University Kolkata, Action Area II, Kadampukur Village, Rajarhat, Newtown, Kolkata, West Bengal 700135, India.
Int J Biochem Cell Biol. 2021 Feb;131:105904. doi: 10.1016/j.biocel.2020.105904. Epub 2020 Dec 24.
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.
一氧化氮是一种非常著名的气态第二信使分子和血管舒张剂，参与体内的多种信号转导，如神经递质传递、离子通道调节和炎症调节。然而，在体内的几种病理条件下，已经报道了一氧化氮应激下可还原的半胱氨酸残基巯基的可逆共价结合导致异常的蛋白质 S-亚硝基化（PSNO），这些病理条件源于神经退行性疾病、癌症、心血管系统和免疫系统紊乱。在细胞中，PSNOs 部分不稳定，并转化为更稳定的二硫键状态，作为形成二硫键的中间步骤，从而引发生物学反应。科学家已经鉴定出几种细胞依赖巯基的二硫键还原酶，它们具有内在的能力通过还原 PSNOs 中形成的稳定二硫键来逆转修饰，从而挽救 S-亚硝基化诱导的蛋白质改变。这些主要的细胞普遍存在的 S-脱亚硝基酶的生理作用及其可能的实施尚未得到充分探索。本综述从当前的研究和发展中获得知识，深入了解主要的普遍存在的 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。该综述涵盖了硫氧还蛋白、TRP14 和谷胱甘肽还原酶系统的机制，并强调了它们在不同细胞条件下的底物特异性、生理作用以及在疾病条件下的重要性，这将使研究人员能够研究针对与硝化应激相关的疾病和紊乱的有效治疗干预措施。
