Department of Pathology and Laboratory Medicine, University of Vermont, Burlington, Vermont.
Department of Medicine, University of Vermont, Burlington, Vermont.
Am J Physiol Cell Physiol. 2020 Feb 1;318(2):C304-C327. doi: 10.1152/ajpcell.00410.2019. Epub 2019 Nov 6.
Glutathione is a major redox buffer, reaching millimolar concentrations within cells and high micromolar concentrations in airways. While glutathione has been traditionally known as an antioxidant defense mechanism that protects the lung tissue from oxidative stress, glutathione more recently has become recognized for its ability to become covalently conjugated to reactive cysteines within proteins, a modification known as glutathionylation (or glutathiolation or protein mixed disulfide). glutathionylation has the potential to change the structure and function of the target protein, owing to its size (the addition of three amino acids) and charge (glutamic acid). glutathionylation also protects proteins from irreversible oxidation, allowing them to be enzymatically regenerated. Numerous enzymes have been identified to catalyze the glutathionylation/deglutathionylation reactions, including glutathione transferases and glutaredoxins. Although protein glutathionylation has been implicated in numerous biological processes, glutathionylated proteomes have largely remained unknown. In this paper, we focus on the pathways that regulate GSH homeostasis, glutathionylated proteins, and glutaredoxins, and we review methods required toward identification of glutathionylated proteomes. Finally, we present the latest findings on the role of glutathionylation/glutaredoxins in various lung diseases: idiopathic pulmonary fibrosis, asthma, and chronic obstructive pulmonary disease.
谷胱甘肽是一种主要的氧化还原缓冲剂，在细胞内达到毫摩尔浓度，在气道内达到高微摩尔浓度。虽然谷胱甘肽传统上被认为是一种抗氧化防御机制，可以保护肺组织免受氧化应激，但最近人们发现，它还能够与蛋白质中的反应性半胱氨酸发生共价结合，这种修饰被称为谷胱甘肽化（或谷胱甘硫醚化或蛋白质混合二硫键）。由于其大小（增加了三个氨基酸）和电荷（谷氨酸），谷胱甘肽化有可能改变靶蛋白的结构和功能。谷胱甘肽化还可以保护蛋白质免受不可逆氧化，从而使其能够被酶促再生。已经鉴定出许多酶来催化谷胱甘肽化/去谷胱甘肽化反应，包括谷胱甘肽转移酶和谷氧还蛋白。尽管蛋白质谷胱甘肽化已被牵涉到许多生物过程中，但谷胱甘肽化蛋白质组在很大程度上仍然未知。在本文中，我们重点介绍了调节 GSH 动态平衡、谷胱甘肽化蛋白和谷氧还蛋白的途径，并回顾了鉴定谷胱甘肽化蛋白质组所需的方法。最后，我们介绍了谷胱甘肽化/谷氧还蛋白在各种肺部疾病中的最新作用：特发性肺纤维化、哮喘和慢性阻塞性肺疾病。
