IF1 function in situ in uncoupler-challenged ischemic rabbit, rat, and pigeon hearts
IF1 function in situ in uncoupler-challenged ischemic rabbit, rat, and pigeon hearts
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DOI：
10.1074/jbc.271.39.23638
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发表时间：
1996-09-27
影响因子：
4.8
通讯作者：
Broge, CW
中科院分区：
文献类型：
--
作者：
Rouslin, W;Broge, CW
兔、大鼠和鸽子分别是三种心肌线粒体ATP酶调节类别a、B和c的代表物种。a类物种在其心肌线粒体中含有完整的高亲和力ATP酶抑制剂亚基IF1，并且在心肌缺血期间显示出显著的IF1介导的线粒体ATP酶抑制。B类物质含有低水平的高亲和力IF1，并且在缺血期间显示出非常少的IF1介导的ATP酶抑制。C类物种含有低亲和力形式的IF1的完整补体，并在缺血期间显示低至中等水平的IF1介导的ATP酶抑制。在本研究中，我们在使其缺血之前，通过冠状动脉用解偶联剂羰基氰化物对三氟甲氧基苯腙（FCCP）灌注每个调节类成员的心脏，然后，我们比较了FCCP处理的心脏与同样处理的无FCCP心脏在缺血期间细胞ATP消耗的净速率，因此，我们测试了这三个物种心肌线粒体的相对能力，以避免由于ATP引起的细胞ATP耗竭的净速率的潜在大幅增加。我们发现FCCP原位解偶联对兔心脏缺血期间ATP消耗的影响相对较小，它显著加速缺血大鼠心脏中ATP消耗，并且它对缺血鸽子心脏中GTP消耗具有中等影响。这些结果首次证明了IF1介导的线粒体ATP酶抑制可以减缓细胞ATP耗竭的相对程度，这是由于这三类心脏中的线粒体ATP酶完全解偶联。他们表明，与兔子心脏的情况相反，在这些条件下，大鼠心肌线粒体中存在的低水平的高亲和力IF1基本上是无功能的，而鸽子心肌线粒体中存在的低亲和力形式的IF1的完全补体是部分功能性的，耗尽
Rabbit, rat, and pigeon are species representative of three cardiac muscle mitochondrial ATPase regulatory classes, a, b and c, respectively, Class a species contain a full complement of higher affinity ATPase inhibitor subunit, IF1, in their cardiac muscle mitochondria and show marked IF1-mediated mitochondrial ATPase inhibition during myocardial ischemia. Class b species contain low levels of higher affinity IF1 and show very little IF1-mediated ATPase inhibition during ischemia. Class c species contain a full complement of a lower affinity form of IF1 and show a low-to-moderate level of IF1-mediated ATPase inhibition during ischemia, In the present study we perfused hearts of a member of each regulatory class through the coronary arteries with the uncoupler, carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), before making them ischemic, We then compared net rates of cell ATP depletion during ischemia in the FCCP-treated hearts to identically treated FCCP-free hearts, Thus, we tested the relative capacities of cardiac muscle mitochondria of the three species to avert a potentially greatly increased net rate of cell ATP depletion due to ATP hydrolysis by the fully uncoupled mitochondrial ATPase, We found that FCCP-uncoupling in situ had a relatively small effect on ATP depletion during ischemia in rabbit hearts, that it dramatically accelerated ATP depletion in ischemic rat hearts, and that it had an intermediate effect on GTP depletion in ischemic pigeon hearts. These results demonstrate for the first time the relative extents to which IF1-mediated mitochondrial ATPase inhibition can slow cell ATP depletion due to the fully uncoupled mitochondrial ATPase in these three classes of hearts. They show that, in contrast to the situation in rabbit hearts, the low level of higher affinity IF1 present in the cardiac muscle mitochondria of the rat is, under these conditions, essentially nonfunctional, while the full complement of the lower affinity form of IF1 present in the cardiac muscle mitochondria of the pigeon is partially functional in that it appeared to provide an intermediate level of protection against rapid cell ATP depletion.