PERMEABILIZATION OF THE INNER MITOCHONDRIAL-MEMBRANE BY CA2+ IONS IS STIMULATED BY T-BUTYL HYDROPEROXIDE AND MEDIATED BY REACTIVE OXYGEN SPECIES GENERATED BY MITOCHONDRIA
PERMEABILIZATION OF THE INNER MITOCHONDRIAL-MEMBRANE BY CA2+ IONS IS STIMULATED BY T-BUTYL HYDROPEROXIDE AND MEDIATED BY REACTIVE OXYGEN SPECIES GENERATED BY MITOCHONDRIA
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DOI：
10.1016/0891-5849(94)00166-h
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发表时间：
1995-03-01
影响因子：
7.4
通讯作者：
VERCESI, AE
中科院分区：
文献类型：
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作者：
CASTILHO, RF;KOWALTOWSKI, AJ;VERCESI, AE
在KCl/蔗糖培养基中，Ca2+单独存在或Ca2+和过氧化氢t-丁基存在时，失电线粒体的肿胀程度随着反应介质中分子氧浓度的降低而降低；在厌氧状态下不发生肿胀。这种肿胀也被外源性过氧化氢酶或Fe2+螯合剂邻菲罗啉以一种时间依赖性的方式抑制。当线粒体在厌氧培养基中孵育或存在邻菲罗啉时，导致Ca2+和t-丁基过氧化氢诱导的蛋白质聚集体形成的蛋白质硫醇交联的产生不会发生。此外，研究还表明，用t-丁基过氧化氢和自旋捕集器DMPO处理大鼠肝脏线粒体得到的稳定甲基自由基加合物的产率因添加EGTA而降低，而因添加Ca2+离子而增加。这些数据支持Ca2+离子刺激呼吸链电子泄漏的假设，增加线粒体活性氧的产生。
The extent of swelling undergone by deenergized mitochondria incubated in KCl/sucrose medium in the presence of Ca2+ alone or Ca2+ and t-butyl hydroperoxide decreases by decreasing molecular oxygen concentration in the reaction medium; under anaerobiosis no swelling occurs. This swelling is also inhibited by the presence of exogenous catalase or by the Fe2+ chelator o-phenanthroline in a time-dependent manner. The production of protein thiol cross-linking that leads to the formation of protein aggregates induced by Ca2+ and t-butyl hydroperoxide does not occur when mitochondria are incubated in anaerobic medium or in the presence of o-phenanthroline. In addition, it is also shown that the yield of stable methyl radical adducts, obtained from rat liver mitochondria treated with t-butyl hydroperoxide and the spin trap DMPO, is reduced by addition of EGTA and increases by addition of Ca2+ ions. These data support the hypothesis that Ca2+ ions stimulate electron leakage from the respiratory chain, increasing the mitochondrial production of reactive oxygen species.