Role of glycogen synthase kinase-3beta in cardioprotection.
Role of glycogen synthase kinase-3beta in cardioprotection.
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DOI：
10.1161/circresaha.109.197996
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发表时间：
2009-06-05
影响因子：
20.1
通讯作者：
Sollott SJ
中科院分区：
文献类型：
--
作者：
Juhaszova M;Zorov DB;Yaniv Y;Nuss HB;Wang S;Sollott SJ
Limitation of infarct size by ischemic/pharmacological pre- and post-conditioning involves activation of a complex set of cell-signaling pathways. Multiple lines of evidence implicate the mitochondrial permeability transition pore (mPTP) as a key end-effector of ischemic/pharmacological pre- as well as post-conditioning. Increasing the ROS-threshold for mPTP-induction enhances the resistance of cardiomyocytes to oxidant stress and results in infarct size reduction. Here we survey and synthesize the current knowledge about the role of glycogen synthase kinase-3β (GSK-3β) in cardioprotection, including pre- and post-conditioning. Activation of a wide spectrum of cardioprotective signaling pathways is associated with phosphorylation and inhibition of a discrete pool of GSK-3β relevant to mitochondrial signaling. Therefore, GSK-3β has emerged as the integration point of many of these pathways and plays a central role in transferring protective signals downstream to target(s) that act at or in proximity to the mPTP. Bcl-2-family proteins and mPTP-regulatory elements such as ANT and CyP-D (possibly VDAC) may be the functional downstream target(s) of GSK-3β. Gaining a better understanding of these interactions to control and prevent mPTP-induction when appropriate will enable us to decrease the negative impact of the reperfusion-induced ROS-burst on the fate of mitochondria and perhaps allow us to limit propagation of damage throughout and between cells and consequently, to better limit infarct size.
