CaMKII is a nodal signal for multiple programmed cell death pathways in heart.
CaMKII is a nodal signal for multiple programmed cell death pathways in heart.
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DOI：
10.1016/j.yjmcc.2016.12.007
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发表时间：
2017-02
影响因子：
5
通讯作者：
Anderson ME
中科院分区：
文献类型：
--
作者：
Feng N;Anderson ME
持续的Ca 2 +/钙调蛋白依赖性激酶II（CaMKII）激活在多种心脏疾病的发病机制中发挥着核心作用。新出现的证据表明，CaMKII诱发的程序性细胞死亡，包括细胞凋亡和坏死性凋亡，是持续CaMKII激活的有害作用的关键潜在机制之一。CaMKII整合β-肾上腺素能、Gq偶联受体、活性氧（ROS）、高血糖和促死亡细胞因子信号传导，以通过内源性和外源性途径引起心肌细胞凋亡。新的证据表明，CaMK Ⅱ也是受体相互作用丝氨酸/苏氨酸激酶3（RIP 3）诱导心肌坏死性凋亡的关键介质。CaMKII在细胞死亡中的作用取决于亚细胞定位，并且在同种型和剪接变体之间变化。虽然CaMKII现在是一种广泛验证的促进心肌细胞死亡的节点信号，但上游和下游途径和靶点仍不完全清楚，需要进一步研究。
Sustained Ca2+/calmodulin dependent kinase II (CaMKII) activation plays a central role in the pathogenesis of a variety of cardiac diseases. Emerging evidence suggests CaMKII evoked programmed cell death, including apoptosis and necroptosis, is one of the key underlying mechanisms for the detrimental effect of sustained CaMKII activation. CaMKII integrates β-adrenergic, Gq coupled receptor, reactive oxygen species (ROS), hyperglycemia, and pro-death cytokine signaling to elicit myocardial apoptosis by intrinsic and extrinsic pathways. New evidence demonstrates CaMKII is also a key mediator of receptor interacting serine/threonine kinase 3 (RIP3) induced myocardial necroptosis. The role of CaMKII in cell death is dependent upon subcellular localization and varies across isoforms and splice variants. While CaMKII is now an extensively validated nodal signal for promoting cardiac myocyte death, the upstream and downstream pathways and targets remain incompletely understood, demanding further investigation.