Ascorbate and low concentrations of FeSO4 induce the Ca2+-dependent pore in rat liver mitochondria
Ascorbate and low concentrations of FeSO4 induce the Ca2+-dependent pore in rat liver mitochondria
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DOI：
10.1023/a:1011913021380
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发表时间：
2001-08-01
影响因子：
2.8
通讯作者：
Mokhova, EN
中科院分区：
文献类型：
--
作者：
Brailovskaya, IV;Starkov, AA;Mokhova, EN
氧化应激是各种病理中组织和细胞损伤的最常见原因之一。研究了低浓度硫酸亚铁和维生素C体外诱导的氧化应激条件下线粒体损伤的分子机制。将FeSO 4（1-4 μ M）加入到在2.3 mM抗坏血酸存在下孵育的大鼠肝线粒体中，诱导（有一定延迟）膜电位降低和高幅度肿胀。同时，它也显著降低了线粒体积累外源性Ca ~（2+）的能力。FeSO 4+抗坏血酸盐的所有作用基本上都被环孢菌素A阻止，环孢菌素A是线粒体Ca 2+依赖性孔（也称为线粒体渗透性转变）的特异性抑制剂。EGTA恢复线粒体的膜电位与FeSO 4+抗坏血酸断电。我们推测，在体外诱导的氧化应激与FeSO 4和毫摩尔浓度的抗坏血酸通过诱导线粒体内膜中的环孢菌素A敏感的Ca 2+依赖性孔损伤线粒体。
Oxidative stress is one of the most frequent causes of tissue and cell injury in various pathologies. The molecular mechanism of mitochondrial damage under conditions of oxidative stress induced in vitro with low concentrations of FeSO4 and ascorbate (vitamin C) was studied. FeSO4 (1-4 muM) added to rat liver mitochondria that were incubated in the presence of 2.3 mM ascorbate induced (with a certain delay) a decrease in membrane potential and high-amplitude swelling. It also significantly decreased the ability of mitochondria to accumulate exogenous Ca2+. All the effects of FeSO4 + ascorbate were essentially prevented by cyclosporin A, a specific inhibitor of the mitochondrial Ca2+-dependent pore (also known as the mitochondrial permeability transition). EGTA restored the membrane potential of mitochondria de-energized with FeSO4 + ascorbate. We hypothesize that oxidative stress induced in vitro with FeSO4 and millimolar concentrations of ascorbate damages mitochondria by inducing the cyclosporin A-sensitive Ca2+-dependent pore in the inner mitochondrial membrane.