Navet Rachel, Mouithys-Mickalad Ange, Douette Pierre, Sluse-Goffart Claudine M, Jarmuszkiewicz Wieslawa, Sluse Francis E
Laboratory of Bioenergetics, Oxygen Biochemistry Centre, University of Liege, Sart Tilman B6c, 4000 Liege, Belgium.
J Bioenerg Biomembr. 2006 Feb;38(1):23-32. doi: 10.1007/s10863-006-9002-9.
Superoxide anion generation and the impairment of oxidative phosphorylation yield were studied in rat skeletal muscle mitochondria submitted to anoxia/reoxygenation in vitro. Production of superoxide anion was detected after several cycles of anoxia/reoxygenation. Concomitantly, a decrease of state 3 respiration and phosphorylation yield (ADP/O) were observed. The latter resulted from a proton leak. The presence of palmitic acid during anoxia/reoxygenation cycles led to a dose-dependent inhibition of superoxide anion production together with a partial protection of the ADP/O ratio measured after anoxia/reoxygenation. The ADP/O decrease was shown to be due to a permeability transition pore-sustained proton leak, as it was suppressed by cyclosporine A. The permeability transition pore activation was induced during anoxia/reoxygenation by superoxide anion, as it was cancelled by the spin trap (POBN), which scavenges superoxide anion and by palmitic acid, which induces mitochondrial uncoupling. It can be proposed that the palmitic acid-induced proton leak cancels the production of superoxide anion by mitochondria during anoxia/reoxygenation and therefore prevents the occurrence of the superoxide anion-induced permeability transition pore-mediated proton leak after anoxia/reoxygenation.
在体外经历缺氧/复氧的大鼠骨骼肌线粒体中，研究了超氧阴离子的产生以及氧化磷酸化产率的损伤情况。在几个缺氧/复氧循环后检测到了超氧阴离子的产生。同时，观察到状态3呼吸和磷酸化产率（ADP/O）降低。后者是由质子泄漏导致的。在缺氧/复氧循环期间，棕榈酸的存在导致超氧阴离子产生受到剂量依赖性抑制，同时对缺氧/复氧后测得的ADP/O比值有部分保护作用。ADP/O降低被证明是由于通透性转换孔持续的质子泄漏所致，因为它被环孢素A所抑制。通透性转换孔的激活是在缺氧/复氧期间由超氧阴离子诱导的，因为它被清除超氧阴离子的自旋捕捉剂（POBN）和诱导线粒体解偶联的棕榈酸所消除。可以提出，棕榈酸诱导的质子泄漏消除了缺氧/复氧期间线粒体中超氧阴离子的产生，因此防止了缺氧/复氧后超氧阴离子诱导的通透性转换孔介导的质子泄漏的发生。
