Luczak Elizabeth D, Anderson Mark E
Department of Internal Medicine, Division of Cardiovascular Medicine and Cardiovascular Research Center, Carver College of Medicine, University of Iowa, Iowa City, USA.
Department of Internal Medicine, Division of Cardiovascular Medicine and Cardiovascular Research Center, Carver College of Medicine, University of Iowa, Iowa City, USA; Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, USA.
J Mol Cell Cardiol. 2014 Aug;73:112-6. doi: 10.1016/j.yjmcc.2014.02.004. Epub 2014 Feb 13.
Calcium and redox signaling both play important roles in the pathogenesis of cardiac disease; although how these signals are integrated in the heart remains unclear. One putative sensor for both calcium and oxidative stress in the heart is CaMKII, a calcium activated kinase that has recently been shown to also be regulated by oxidation. Oxidative activation of CaMKII occurs in several models of cardiac disease, including myocardial injury and inflammation, excessive neurohumoral activation, atrial fibrillation, and sinus node dysfunction. Additionally, oxidative activation of CaMKII is suggested in subcellular domains where calcium and ROS signaling intersect, such as mitochondria. This review describes the mechanism of activation of CaMKII by oxidation, the cardiac diseases where oxidized CaMKII has been identified, and suggests contexts where oxidized CaMKII is likely to play an important role. This article is part of a Special Issue entitled "Redox Signalling in the Cardiovascular System".
钙信号和氧化还原信号在心脏病发病机制中均发挥重要作用；尽管这些信号在心脏中如何整合尚不清楚。心脏中钙和氧化应激的一个假定传感器是钙调蛋白激酶II（CaMKII），这是一种钙激活激酶，最近已证明它也受氧化作用调节。CaMKII的氧化激活发生在多种心脏病模型中，包括心肌损伤和炎症、过度的神经体液激活、心房颤动和窦房结功能障碍。此外，在钙信号和活性氧（ROS）信号相交的亚细胞区域，如线粒体中，也提示存在CaMKII的氧化激活。本综述描述了CaMKII氧化激活的机制、已鉴定出氧化型CaMKII的心脏病，并提出了氧化型CaMKII可能发挥重要作用的背景。本文是名为“心血管系统中的氧化还原信号”的特刊的一部分。
