Increased calcium vulnerability of senescent cardiac mitochondria: protective role for a mitochondrial potassium channel opener
Increased calcium vulnerability of senescent cardiac mitochondria: protective role for a mitochondrial potassium channel opener
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DOI：
10.1016/s0047-6374(01)00242-1
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发表时间：
2001-07-31
影响因子：
5.3
通讯作者：
Terzic, A
中科院分区：
文献类型：
--
作者：
Jahangir, A;Ozcan, C;Terzic, A
在衰老过程中，内源性心脏保护机制明显减弱，导致对缺血再灌注的脆弱性增加。特别是，线粒体，这是必不可少的维持心脏能量和离子的稳态，是容易受到Ca 2+超载，代谢损伤的一个组成部分。然而，缺乏保护衰老线粒体的有效手段。在这里，线粒体的功能和结构进行了评估，使用离子选择性微电极，高效液相色谱和电子显微镜。衰老降低ADP诱导的耗氧量，延长ADP转化为ATP的时间，表现为氧化磷酸化速率降低。衰老还减少了线粒体Ca 2+处理，并增加了Ca 2+诱导的线粒体损伤。二氮嗪，钾通道开放剂，减少钙离子负荷和保护衰老线粒体的功能和结构的完整性，从钙离子诱导的损伤。通过这种方式，本研究确定了药物治疗在保护脆弱的衰老线粒体免受Ca 2+过载条件下的潜在有用性，例如：缺血-再灌注。(C)2001爱思唯尔科学爱尔兰有限公司保留所有权利。
In senescence, endogenous mechanisms of cardioprotection are apparently attenuated resulting in increased vulnerability to ischemia-reperfusion. In particular, mitochondria, which are essential in maintaining cardiac energetic and ionic homeostasis, are susceptible to Ca2+ overload, a component of metabolic injury. However, effective means of protecting senescent mitochondria are lacking. Here, mitochondrial function and structure were assessed using ion-selective mini-electrodes, high-performance liquid chromatography and electron microscopy. Aging decreased ADP-induced oxygen consumption and prolonged the time associated with ADP to ATP conversion, which manifested as a reduced rate of oxidative phosphorylation. Aging also reduced mitochondrial Ca2+ handling, and increased Ca2+-induced mitochondrial damage. Diazoxide, a potassium channel opener, reduced Ca2+ loading and protected the functional and structural integrity of senescent mitochondria from Ca2+-induced injury. In this way, the present study identifies the potential usefulness for pharmacotherapy in protecting vulnerable senescent mitochondria from conditions of Ca2+ overload, such as: ischemia-reperfusion. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.