Hibernation during hypoxia in cardiomyocytes -: Role of mitochondria as the O2 sensor
Hibernation during hypoxia in cardiomyocytes -: Role of mitochondria as the O2 sensor
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DOI：
10.1074/jbc.273.6.3320
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发表时间：
1998-02-06
影响因子：
4.8
通讯作者：
Schumacker, PT
中科院分区：
文献类型：
--
作者：
Budinger, GRS;Duranteau, J;Schumacker, PT
在心肌冬眠期间，冠状动脉灌注减少会引起收缩抑制，表明能量需求减弱。我们之前发现心肌细胞缺氧（3% O-2；PO2 = 20 torr，持续>2小时）期间收缩和 O-2 消耗受到抑制，在复氧后是可逆的。本研究试图确定线粒体是否作为细胞 O-2 传感器介导这种反应。在受控 O-2 条件下研究胚胎心肌细胞。使用四甲基罗丹明乙酯 (TMRE) 评估，缺氧不会导致线粒体电位急剧下降。使用镁绿探针进行评估，细胞 [ATP] 在缺氧期间得以保留。因此，ATP 的合成和利用仍然紧密结合。适应缺氧>2小时的细胞在复氧后表现出线粒体电位增加4%，表明细胞色素c氧化酶存在部分抑制。为了测试氧化酶是否充当 O-2 传感器，施用叠氮化物 (1 mM) 通过降低氧化酶的 V-max 来模拟缺氧的影响。叠氮化物对收缩和线粒体电位的影响模仿了对缺氧的反应。我们的结论是，缺氧期间细胞色素氧化酶的部分抑制使线粒体能够充当 O-2 传感器，介导缺氧期间 ATP 利用率和 O-2 消耗的减少。
During myocardial hibernation, decreases in coronary perfusion elicit inhibition of contraction, suggesting that energy demand is attenuated. We previously found an inhibition of contraction and O-2 consumption during hypoxia (3% O-2; PO2 = 20 torr for >2 h) in cardiomyocytes, which was reversible after reoxygenation. This study sought to determine whether mitochondria function as cellular O-2 sensors mediating this response. Embryonic cardiomyocytes were studied under controlled O-2 conditions. Hypoxia produced no acute decrease in mitochondrial potential as assessed using tetramethylrhodamine ethylester (TMRE). Cellular [ATP] was preserved throughout hypoxia, as assessed using the probe Magnesium Green. Thus, ATP synthesis and utilization remained closely coupled. Cells adapted to hypoxia for >2 h exhibited a 4% increase in mitochon drial potential upon reoxygenation, suggesting that a partial inhibition of cytochrome c oxidase had existed. To test whether the oxidase serves as an O-2 sensor, azide was administered (1 mM) to simulate the effects of hypoxia by lowering the V-max of the oxidase. The effects of azide on contraction and mitochondrial potential mimicked the response to hypoxia. We conclude that partial inhibition of cytochrome oxidase during hypoxia allows mitochondria to function as the O-2 sensor mediating the decreases in ATP utilization and O-2 consumption during hypoxia.