Blockade of electron transport before cardiac ischemia with the reversible inhibitor amobarbital protects rat heart mitochondria
Blockade of electron transport before cardiac ischemia with the reversible inhibitor amobarbital protects rat heart mitochondria
复制标题
DOI：
10.1124/jpet.105.091702
复制
发表时间：
2006-01-01
影响因子：
3.5
通讯作者：
Lesnefsky, EJ
中科院分区：
文献类型：
--
作者：
Chen, Q;Hoppel, CL;Lesnefsky, EJ
心肌缺血损伤线粒体电子传递链。鱼藤酮不可逆地阻断复合物I的电子传递，通过减少细胞色素c的损失和通过细胞色素氧化酶保护呼吸来减少心肌线粒体的缺血性损伤。在缺血和再灌注期间保护心肌的治疗性干预需要使用可逆抑制剂，其允许在再灌注期间恢复氧化代谢。异戊巴比妥是复合物I的鱼藤酮位点的可逆抑制剂。我们询问在缺血前立即给予异戊巴比妥是否可以保护呼吸功能。将离体大鼠心脏在37 ℃下灌注15分钟，然后进行25分钟的全脑缺血。Amobarbital处理的心脏在缺血前接受药物1分钟。缺血后分离肌膜下（SSM）和原纤维间（IFM）线粒体群体，并测定氧化磷酸化。异戊巴比妥保护氧化磷酸化，包括通过细胞色素氧化酶，在SSM和IFM以剂量依赖性的方式，与2至2.5 mM的最佳剂量。异戊巴比妥还保存细胞色素c含量在SSM和IFM。因此，缺血期间电子传递链的可逆阻断保护线粒体呼吸。
Cardiac ischemia damages the mitochondrial electron transport chain. Irreversible blockade of electron transport at complex I by rotenone decreases ischemic damage to cardiac mitochondria by decreasing the loss of cytochrome c and preserving respiration through cytochrome oxidase. Therapeutic intervention to protect myocardium during ischemia and reperfusion requires the use of a reversible inhibitor that allows resumption of oxidative metabolism during reperfusion. Amobarbital is a reversible inhibitor at the rotenone site of complex I. We asked whether amobarbital administered immediately before ischemia protected respiratory function. Isolated rat hearts were perfused for 15 min followed by 25-min global ischemia at 37 C. Amobarbital-treated hearts received drug for 1 min before ischemia. Subsarcolemmal (SSM) and interfibrillar (IFM) populations of mitochondria were isolated after ischemia, and oxidative phosphorylation was measured. Amobarbital protected oxidative phosphorylation, including through cytochrome oxidase, in both SSM and IFM in a dose-dependent manner, with an optimal dose of 2 to 2.5 mM. Amobarbital also preserved cytochrome c content in both SSM and IFM. Thus, reversible blockade of the electron transport chain during ischemia protects mitochondrial respiration.