Oxygen at physiological concentrations. A potential, paradoxical mediator of reperfusion injury to mitochondria induced by phosphate.
Oxygen at physiological concentrations. A potential, paradoxical mediator of reperfusion injury to mitochondria induced by phosphate.
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生理浓度的氧气。
DOI：
10.1172/jci111289
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Sobel,BE
中科院分区：
文献类型：
--
作者：
Lange,LG;Hartman,M;Sobel,BE
心肌缺血后再灌注引起的细胞损伤表现为显著的线粒体损伤以及其他标志，如收缩带坏死。钙在几个系统中被认为是不可逆细胞损伤的介质。为了确定与再灌注相关的线粒体损伤的其他潜在介质，在体外评价了无机磷酸盐、氧和从兔心脏收获的线粒体之间的相互作用。线粒体表现出快速失活的氧化磷酸化预孵育后，在25摄氏度时，磷酸盐和氧气。EDTA、EGTA、镁、地尔硫卓或钌红可部分但不完全阻止失活，结果与其他研究结果一致，表明钙有害流入线粒体;外源性钙可增强失活。然而，目前的数据表明，失活是防止在没有氧气的情况下通过孵育线粒体，并首次证明，损伤引起的磷酸盐是依赖于氧在生理浓度，因为钙和/或磷酸盐流入与有氧代谢或因为氧对线粒体产生有害影响，这可能使他们特别容易受到钙流入。由于细胞内无机磷酸盐浓度增加显着缺血，再灌注与含氧介质可能矛盾地增加线粒体损伤在这种情况下。因此，在缺血诱导的细胞内钙和磷酸盐浓度增加的情况下，随后细胞内氧张力生理水平的重建可能促进线粒体损伤，已知线粒体损伤随着再灌注而增加。
Cellular injury induced by reperfusion after myocardial ischemia is manifested by striking mitochondrial damage as well as other hallmarks such as contraction band necrosis. Calcium has been implicated as a mediator of irreversible cellular injury in several systems. To identify other potential mediators of the mitochondrial injury associated with reperfusion, interactions between inorganic phosphate, oxygen, and mitochondria harvested from rabbit hearts were evaluated in vitro. Mitochondria exhibited rapid inactivation of oxidative phosphorylation after preincubation at 25 degrees C when phosphate and oxygen were present. Inactivation was partially but not completely precluded by EDTA, EGTA, magnesium, diltiazem, or ruthenium red, results in concert with findings of others suggesting involvement of a deleterious influx of calcium into mitochondria; exogenous calcium enhanced inactivation. However, the present data indicate that inactivation is prevented by incubation of mitochondria in the absence of oxygen, and demonstrate for the first time that injury elicited by phosphate is dependent on oxygen at physiological concentrations either because calcium and/or phosphate influx is linked to aerobic metabolism or because oxygen exerts deleterious effects on mitochondria, which may render them particularly susceptible to calcium influx. Since intracellular inorganic phosphate concentration increases markedly with ischemia, reperfusion with oxygenated medium may paradoxically augment mitochondrial injury in this setting. Thus, in the presence of increased intracellular concentrations of calcium and phosphate induced by ischemia, subsequent reestablishment of physiological levels of intracellular oxygen tension may promote mitochondrial damage, which is known to increase with reperfusion.