Murphy Elizabeth
Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, US Department of Health and Human Services, Research Triangle Park, NC, USA.
Circ Res. 2004 Jan 9;94(1):7-16. doi: 10.1161/01.RES.0000108082.76667.F4.
Cardioprotective mechanisms such as acute or early preconditioning activate several primary signaling pathways that seem to converge on mitochondrial targets, leading to altered cell metabolism and inhibition of apoptosis. Acute preconditioning leads to generation of agonists, which bind to G protein-coupled receptors, and initiates a signaling cascade that involves activation of phosphoinositide-3-kinase, endothelial NO synthase, protein kinase C, glycogen synthase kinase 3beta, mitogen-activated protein kinases, and other signaling pathways. Activation of these signaling pathways along with generation of reactive oxygen species leads to alterations in the activity of key mitochondrial proteins such as mitochondrial ATP-sensitive K(+) channels, the mitochondrial permeability transition pore, and bcl-2 family members. Alterations in these mitochondrial proteins results in altered metabolism and inhibition of cell death, thus resulting in cardioprotection.
诸如急性或早期预处理等心脏保护机制会激活多个主要信号通路，这些信号通路似乎汇聚于线粒体靶点，从而导致细胞代谢改变并抑制细胞凋亡。急性预处理会导致激动剂的产生，这些激动剂与G蛋白偶联受体结合，并启动一个信号级联反应，该反应涉及磷酸肌醇-3-激酶、内皮型一氧化氮合酶、蛋白激酶C、糖原合酶激酶3β、丝裂原活化蛋白激酶及其他信号通路的激活。这些信号通路的激活以及活性氧的产生会导致关键线粒体蛋白（如线粒体ATP敏感性钾通道、线粒体通透性转换孔和bcl-2家族成员）的活性发生改变。这些线粒体蛋白的改变会导致代谢改变并抑制细胞死亡，从而实现心脏保护。
