Hexokinases and cardioprotection.

Hexokinases and cardioprotection.
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DOI:
10.1016/j.yjmcc.2014.09.020
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发表时间:
2015-01
影响因子:
5
通讯作者:
Weiss, James N.
Weiss, James N.
中科院分区:
医学2区
文献类型:
--
作者:
Calmettes, Guillaume;Ribalet, Bernard;John, Scott;Korge, Paavo;Ping, Peipei;Weiss, James N.

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作为葡萄糖代谢中第一个酶促步骤的介体,己糖激酶(HK)协调葡萄糖的各种分解代谢和合成代谢用途,通过产生用于谷胱甘肽还原的NADPH来调节抗氧化能力,并通过与电压依赖性阴离子通道(VDAC)(线粒体通透性转换孔(mPTP)的调节组分)直接相互作用来调节细胞死亡过程。本文综述了HK在心肌缺血再灌注损伤中的作用,包括:1)不同HK亚型的特性及其亚细胞定位对HK功能的调节; 2)HK在I/R过程中对葡萄糖代谢和能量产生的调节; 3)HK影响mPTP开放和I/R过程中细胞损伤的分子机制; 4)不同的代谢和HK谱如何与癌细胞、新生儿心脏和正常、肥大和衰竭的成人心脏中对I/R损伤的易感性和心脏保护功效相关,以及这些差异如何指导限制心脏I/R损伤的新治疗策略。
As mediators of the first enzymatic step in glucose metabolism, hexokinases (HKs) orchestrate a variety of catabolic and anabolic uses of glucose, regulate antioxidant power by generating NADPH for glutathione reduction, and modulate cell death processes by directly interacting with the voltage-dependent anion channel (VDAC), a regulatory component of the mitochondrial permeability transition pore (mPTP). Here we summarize the current state-of-knowledge about HKs and their role in protecting the heart from ischemia/reperfusion (I/R) injury, reviewing: 1) the properties of different HK isoforms and how their function is regulated by their subcellular localization; 2) how HKs modulate glucose metabolism and energy production during I/R; 3) the molecular mechanisms by which HKs influence mPTP opening and cellular injury during I/R; 4) how different metabolic and HK profiles correlate with susceptibility to I/R injury and cardioprotective efficacy in cancer cells, neonatal hearts, and normal, hypertrophied and failing adult hearts, and how these difference may guide novel therapeutic strategies to limit I/R injury in the heart.
DOI: 10.1085/jgp.201310968
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期刊: The Journal of general physiology
影响因子: --
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