Paradies Giuseppe, Petrosillo Giuseppe, Pistolese Marilva, Di Venosa Nicola, Federici Antonio, Ruggiero Francesca Maria
Department of Biochemistry and Molecular Biology and CNR Institute of Biomembranes and Bioenergetics, University of Bari, Bari, Italy.
Circ Res. 2004 Jan 9;94(1):53-9. doi: 10.1161/01.RES.0000109416.56608.64. Epub 2003 Dec 1.
Reactive oxygen species (ROS) are considered an important factor in ischemia/reperfusion injury to cardiac myocytes. Mitochondrial respiration is an important source of ROS production and hence a potential contributor to cardiac reperfusion injury. In this study, we have examined the effect of ischemia and ischemia followed by reperfusion of rat hearts on various parameters related to mitochondrial function, such as complex I activity, oxygen consumption, ROS production, and cardiolipin content. The activity of complex I was reduced by 25% and 48% in mitochondria isolated from ischemic and reperfused rat heart, respectively, compared with the controls. These changes in complex I activity were associated with parallel changes in state 3 respiration. The capacity of mitochondria to produce H2O2 increased on reperfusion. The mitochondrial content of cardiolipin, which is required for optimal activity of complex I, decreased by 28% and 50% as function of ischemia and reperfusion, respectively. The lower complex I activity in mitochondria from reperfused rat heart could be completely restored to the level of normal heart by exogenous added cardiolipin. This effect of cardiolipin could not be replaced by other phospholipids nor by peroxidized cardiolipin. It is proposed that the defect in complex I activity in ischemic/reperfused rat heart could be ascribed to a ROS-induced cardiolipin damage. These findings may provide an explanation for some of the factors responsible for myocardial reperfusion injury.
活性氧(ROS)被认为是心肌细胞缺血/再灌注损伤的一个重要因素。线粒体呼吸是ROS产生的重要来源,因此是心脏再灌注损伤的一个潜在因素。在本研究中,我们检测了大鼠心脏缺血及缺血后再灌注对与线粒体功能相关的各种参数的影响,如复合体I活性、氧消耗、ROS产生和心磷脂含量。与对照组相比,从缺血和再灌注大鼠心脏分离的线粒体中,复合体I的活性分别降低了25%和48%。复合体I活性的这些变化与状态3呼吸的平行变化相关。再灌注时线粒体产生过氧化氢的能力增加。对于复合体I的最佳活性所必需的心磷脂,其线粒体含量分别因缺血和再灌注而降低了28%和50%。通过外源添加心磷脂,再灌注大鼠心脏线粒体中较低的复合体I活性可完全恢复到正常心脏的水平。心磷脂的这种作用不能被其他磷脂或过氧化心磷脂所替代。有人提出,缺血/再灌注大鼠心脏中复合体I活性的缺陷可能归因于ROS诱导的心磷脂损伤。这些发现可能为一些导致心肌再灌注损伤的因素提供一种解释。