MITOCHONDRIAL COMPLEX-I, COMPLEX-II, COMPLEX-III, COMPLEX-IV, AND COMPLEX-V, IN MYOCARDIAL ISCHEMIA AND AUTOLYSIS
MITOCHONDRIAL COMPLEX-I, COMPLEX-II, COMPLEX-III, COMPLEX-IV, AND COMPLEX-V, IN MYOCARDIAL ISCHEMIA AND AUTOLYSIS
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DOI：
10.1152/ajpheart.1983.244.6.h743
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发表时间：
1983-01-01
影响因子：
--
通讯作者：
ROUSLIN, W
中科院分区：
文献类型：
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作者：
ROUSLIN, W
结扎麻醉犬左冠状动脉回旋支，造成缺血心肌。通过在37 ℃温育犬左心室的透壁样品来产生自溶心肌。C.在每个模型中，使用插入心肌中层的微组合pH电极连续记录组织pH。测定了5种线粒体内膜电子传递酶复合物和氧化磷酸化酶复合物的活性随缺血或自溶时间的变化。虽然复合物II（琥珀酸辅酶Q还原酶）和IV（细胞色素c氧化酶）的活动是完全稳定的，复合物I（NADH-CoQ还原酶）的活动显着下降，但主要是在缺血或自溶20分钟后。在20分钟及以后，在两种模型中，复合物I的活性的降低与NAD-连接的底物在整个线粒体O2摄取的降低密切相关。复合物III（辅酶QH 2-C还原酶）的活性在缺血或自溶过程中以更渐进的速率下降，其下降速率与琥珀酸支持的O2摄取速率相当。复合物V（寡霉素敏感性ATP酶）的活性下降最快（自溶仅5分钟内下降40%），但在2种模型中超过20分钟后几乎趋于平稳。一个惊人的相似模式的差异酶的不稳定性，观察到在分离的控制线粒体在较低的pH值孵育。线粒体内膜内的差异酶不稳定性，酸中毒的严重程度和酶活性损失的程度之间的连接，和简单的组织自溶作为原位心肌缺血的模拟物的有用性被证明。
Ischemic myocardium was produced by occluding the left circumflex coronary artery in anesthetized dogs. Autolyzed myocardium was produced by incubating transmural samples of canine left ventricle at 37.degree. C. Tissue pH was recorded continuously in each model using a microcombination pH electrode impaled into the midmyocardium. The activities of the 5 mitochondrial inner membrane enzyme complexes of electron transport and coupled oxidative phosphorylation were assayed as a function of time of ischemia or autolysis. While the activities of complex II (succinate-CoQ reductase) and IV (cytochrome c oxidase) were completely stable, that of complex I (NADH-CoQ reductase) decreased markedly, but largely only after 20 min of ischemia or autolysis. At 20 min and beyond, the decrease in the activity of complex I paralleled closely the decrease in whole mitochondrial O2 uptake with NAD-linked substrates in both models. The activity of complex III (CoQH2-c reductase) decreased at a more gradual rate during ischemia or autolysis, and its rate of decrease paralleled that of succinate-supported O2 uptake. The activity of complex V (oligomycin-sensitive ATPase) decreased most rapidly (by 40% in only 5 min of autolysis) but nearly leveled off beyond 20 min in the 2 models. A strikingly similar pattern of differential enzyme lability was observed in isolated control mitochondria incubated at lowered pH values. Differential enzyme lability within the mitochondrial inner membrane, a connection between severity of acidosis and the degree of enzyme activity loss, and the usefulness of simple tissue autolysis as an analog of in situ myocardial ischemia were demonstrated.