Department of Pharmacology, College of Physicians and Surgeons, Columbia University, 630 W. 168 St, New York, NY 10032, USA.
Circ Res. 2013 Jan 18;112(2):393-405. doi: 10.1161/CIRCRESAHA.111.300496.
Oxidative stress accompanies a wide spectrum of clinically important cardiac disorders, including ischemia/reperfusion, diabetes mellitus, and hypertensive heart disease. Although reactive oxygen species (ROS) can activate signaling pathways that contribute to ischemic preconditioning and cardioprotection, high levels of ROS induce structural modifications of the sarcomere that impact on pump function and the pathogenesis of heart failure. However, the precise nature of the redox-dependent change in contractility is determined by the source/identity of the oxidant species, the level of oxidative stress, and the chemistry/position of oxidant-induced posttranslational modifications on individual proteins within the sarcomere. This review focuses on various ROS-induced posttranslational modifications of myofilament proteins (including direct oxidative modifications of myofilament proteins, myofilament protein phosphorylation by ROS-activated signaling enzymes, and myofilament protein cleavage by ROS-activated proteases) that have been implicated in the control of cardiac contractility.
氧化应激伴随着广泛的临床重要心脏疾病，包括缺血/再灌注、糖尿病和高血压性心脏病。虽然活性氧（ROS）可以激活信号通路，有助于缺血预适应和心脏保护，但高水平的 ROS 会引起肌节的结构改变，从而影响泵功能和心力衰竭的发病机制。然而，收缩性的氧化还原依赖性变化的确切性质取决于氧化剂的来源/身份、氧化应激的水平以及肌节内个别蛋白质的氧化诱导的翻译后修饰的化学/位置。本综述重点介绍了肌球蛋白蛋白的各种 ROS 诱导的翻译后修饰（包括肌球蛋白蛋白的直接氧化修饰、ROS 激活的信号酶对肌球蛋白蛋白的磷酸化以及 ROS 激活的蛋白酶对肌球蛋白蛋白的切割），这些修饰与心脏收缩性的控制有关。
