Yan Liang-Jun
Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, RES-314E, Fort Worth, TX 76107, USA.
Oxid Med Cell Longev. 2014;2014:343154. doi: 10.1155/2014/343154. Epub 2014 May 5.
Protein oxidative or redox modifications induced by reactive oxygen species (ROS) or reactive nitrogen species (RNS) not only can impair protein function, but also can regulate and expand protein function under a variety of stressful conditions. Protein oxidative modifications can generally be classified into two categories: irreversible oxidation and reversible oxidation. While irreversible oxidation usually leads to protein aggregation and degradation, reversible oxidation that usually occurs on protein cysteine residues can often serve as an "on and off" switch that regulates protein function and redox signaling pathways upon stress challenges. In the context of ischemic tolerance, including preconditioning and postconditioning, increasing evidence has indicated that reversible cysteine redox modifications such as S-sulfonation, S-nitrosylation, S-glutathionylation, and disulfide bond formation can serve as a cellular defense mechanism against tissue ischemic injury. In this review, I highlight evidence of cysteine redox modifications as protective measures in ischemic injury, demonstrating that protein redox modifications can serve as a therapeutic target for attenuating tissue ischemic injury. Prospectively, more oxidatively modified proteins will need to be identified that can play protective roles in tissue ischemic injury, in particular, when the oxidative modifications of such identified proteins can be enhanced by pharmacological agents or drugs that are available or to be developed.
由活性氧（ROS）或活性氮（RNS）诱导的蛋白质氧化或氧化还原修饰不仅会损害蛋白质功能，还能在各种应激条件下调节并扩展蛋白质功能。蛋白质氧化修饰通常可分为两类：不可逆氧化和可逆氧化。不可逆氧化通常会导致蛋白质聚集和降解，而通常发生在蛋白质半胱氨酸残基上的可逆氧化常常可作为一个“开关”，在应激挑战时调节蛋白质功能和氧化还原信号通路。在包括预处理和后处理在内的缺血耐受背景下，越来越多的证据表明，诸如S-磺化、S-亚硝基化、S-谷胱甘肽化和二硫键形成等可逆的半胱氨酸氧化还原修饰可作为细胞抵御组织缺血损伤的一种防御机制。在本综述中，我着重介绍半胱氨酸氧化还原修饰作为缺血损伤保护措施的证据，表明蛋白质氧化还原修饰可作为减轻组织缺血损伤的治疗靶点。前瞻性地看，将需要鉴定出更多能在组织缺血损伤中发挥保护作用的氧化修饰蛋白质，特别是当此类已鉴定蛋白质的氧化修饰可通过现有或待开发的药剂或药物增强时。
