Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, Massachusetts, USA.
Compr Physiol. 2015 Apr;5(2):513-30. doi: 10.1002/cphy.c140042.
A precise control of oxidation/reduction of protein thiols is essential for intact cardiac physiology. Irreversible oxidative modifications have been proposed to play a role in the pathogenesis of cardiovascular diseases. An imbalance of redox homeostasis with diminution of antioxidant capacities predisposes the heart to oxidant injury. There is growing interest in endoplasmic reticulum (ER) stress in the cardiovascular field, since perturbation of redox homeostasis in the ER is sufficient to cause ER stress. Because a number of human diseases are related to altered redox homeostasis and defects in protein folding, many research efforts have been devoted in recent years to understanding the structure and enzymatic properties of the thioredoxin superfamily. The thioredoxin superfamily has been well documented as thiol oxidoreductases to exert a role in various cell signaling pathways. The redox properties of the thioredoxin motif account for the different functions of several members of the thioredoxin superfamily. While thioredoxin and glutaredoxin primarily act as antioxidants by reducing protein disulfides and mixed disulfide, another member of the superfamily, protein disulfide isomerase (PDI), can act as an oxidant by forming intrachain disulfide bonds that contribute to proper protein folding. Increasing evidence suggests a pivotal role of PDI in the survival pathway that promotes cardiomyocyte survival and leads to more favorable cardiac remodeling. Thus, the thiol redox state is important for cellular redox signaling and survival pathway in the heart. This review summarizes the key features of major members of the thioredoxin superfamily directly involved in cardiac physiology and pathology.
蛋白质巯基的氧化还原精确控制对于完整的心脏生理学至关重要。不可逆转的氧化修饰被认为在心血管疾病的发病机制中起作用。氧化还原平衡的失衡和抗氧化能力的降低使心脏容易受到氧化剂的损伤。内质网 (ER) 应激在心血管领域越来越受到关注，因为 ER 中氧化还原平衡的扰动足以引起 ER 应激。由于许多人类疾病与氧化还原平衡改变和蛋白质折叠缺陷有关，近年来许多研究都致力于了解硫氧还蛋白超家族的结构和酶学特性。硫氧还蛋白超家族已被充分证明为巯基氧化还原酶，在各种细胞信号通路中发挥作用。硫氧还蛋白基序的氧化还原特性解释了硫氧还蛋白超家族的几个成员的不同功能。虽然硫氧还蛋白和谷氧还蛋白主要通过还原蛋白质二硫键和混合二硫键作为抗氧化剂起作用，但超家族的另一个成员，蛋白质二硫键异构酶 (PDI)，可以通过形成有助于正确蛋白质折叠的链内二硫键作为氧化剂起作用。越来越多的证据表明 PDI 在促进心肌细胞存活和导致更有利的心脏重塑的存活途径中起关键作用。因此，巯基氧化还原状态对于心脏中的细胞氧化还原信号和存活途径很重要。这篇综述总结了直接参与心脏生理学和病理学的硫氧还蛋白超家族的主要成员的关键特征。
