Cardiac reperfusion injury: Aging, lipid peroxidation, and mitochondrial dysfunction
Cardiac reperfusion injury: Aging, lipid peroxidation, and mitochondrial dysfunction
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DOI：
10.1073/pnas.95.2.510
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发表时间：
1998-01-20
影响因子：
11.1
通讯作者：
Szweda, LI
中科院分区：
文献类型：
--
作者：
Lucas, DT;Szweda, LI
心脏再灌注和衰老与线粒体自由基产生速率增加有关，因此线粒体可能是再灌注诱导的氧化损伤的部位，其严重程度可能随着年龄的增长而增加，4-羟基-2-壬烯醛（HNE）是脂质过氧化的主要产物，缺血心脏组织再灌注后浓度增加，可以与酶反应并使其失活，并在体外抑制线粒体呼吸。因此，线粒体蛋白的HNE修饰可能在再灌注期间发生，并导致：为了开始检验这一假设，以Langendorff方式灌注来自8月龄和24月龄大鼠的心脏并使其经历缺血和/或再灌注期，从暴露于缺血（25分钟）的心脏中分离的线粒体的状态3呼吸的速率比对照组低约25%，与年龄无关。再灌注（40分钟）导致从24个月大但不是8个月大的大鼠中分离的心脏中的状态3呼吸的速率进一步下降。此外，线粒体蛋白的HNE修饰（类似于30和44 kDa）仅发生在来自24月龄大鼠的心脏的再灌注期间。因此，HNE修饰的蛋白仅存在于表现出再灌注诱导的功能下降的那些线粒体中。因此，这些研究将线粒体鉴定为再灌注损伤的亚细胞靶点和与年龄相关的损伤易感性增加的位点。
Cardiac reperfusion and aging are associated with increased rates of mitochondrial free radical production, Mitochondria are therefore a likely site of reperfusion-induced oxidative damage, the severity of which may increase with age, 4-Hydroxy-2-nonenal (HNE), a major product of lipid peroxidation, increases in concentration upon reperfusion of ischemic cardiac tissue, can react with and inactivate enzymes, and inhibits mitochondrial respiration in vitro. HNE modification of mitochondrial protein(s) might, therefore, be expected to occur during reperfusion and result in: loss in mitochondrial function, In addition, this process may be more prevalent in aged animals, To begin to test this hypothesis, hearts from 8- and 24-month-old rats were perfused in Langendorff fashion and subjected to periods of ischemia and/or reperfusion, The rate of state 3 respiration of mitochondria isolated from hearts exposed to ischemia (25 min) was approximately 25% less than that of controls, independent of age, Reperfusion (40 min) caused a further decline in the rate of state 3 respiration in hearts isolated from 24- but not 8-month-old rats. Furthermore, HNE modification of mitochondrial protein (similar to 30 and 44 kDa occurred only during reperfusion of hearts from 24-month-old rats, Thus, HNE-modified protein was present in only those mitochondria exhibiting reperfusion-induced declines in function, These studies therefore identify mitochondria as a subcellular target of reperfusion damage and a site of age-related increases in susceptibility to injury.