Department of Biological Chemistry, Johns Hopkins University, Baltimore, MD 21224, USA.
Circ Res. 2013 Jan 18;112(2):382-92. doi: 10.1161/CIRCRESAHA.112.268680.
In the cardiovascular system, changes in oxidative balance can affect many aspects of cellular physiology through redox-signaling. Depending on the magnitude, fluctuations in the cell's production of reactive oxygen and nitrogen species can regulate normal metabolic processes, activate protective mechanisms, or be cytotoxic. Reactive oxygen and nitrogen species can have many effects including the posttranslational modification of proteins at critical cysteine thiols. A subset can act as redox-switches, which elicit functional effects in response to changes in oxidative state. Although the general concepts of redox-signaling have been established, the identity and function of many regulatory switches remains unclear. Characterizing the effects of individual modifications is the key to understand how the cell interprets oxidative signals under physiological and pathological conditions. Here, we review the various cysteine oxidative posttranslational modifications and their ability to function as redox-switches that regulate the cell's response to oxidative stimuli. In addition, we discuss how these modifications have the potential to influence other posttranslational modifications' signaling pathways though cross-talk. Finally, we review the increasing number of tools being developed to identify and quantify the various cysteine oxidative posttranslational modifications and how this will advance our understanding of redox-regulation.
在心血管系统中,氧化平衡的变化可以通过氧化还原信号影响细胞生理学的许多方面。根据幅度的不同,细胞中活性氧和氮物种的产生波动可以调节正常的代谢过程、激活保护机制或产生细胞毒性。活性氧和氮物种可以有许多作用,包括在关键半胱氨酸巯基上进行蛋白质的翻译后修饰。一部分可以作为氧化还原开关,根据氧化状态的变化产生功能效应。尽管氧化还原信号的一般概念已经确立,但许多调节开关的身份和功能仍不清楚。描述单个修饰的作用是理解细胞在生理和病理条件下如何解释氧化信号的关键。在这里,我们回顾了各种半胱氨酸氧化翻译后修饰及其作为氧化还原开关的功能,这些开关调节细胞对氧化刺激的反应。此外,我们还讨论了这些修饰如何通过串扰影响其他翻译后修饰信号通路。最后,我们回顾了为鉴定和量化各种半胱氨酸氧化翻译后修饰而开发的越来越多的工具,以及这将如何促进我们对氧化还原调节的理解。