MITOCHONDRIAL REGULATION OF SUPEROXIDE BY CA2+ - AN ALTERNATE MECHANISM FOR THE CARDIOTOXICITY OF DOXORUBICIN
MITOCHONDRIAL REGULATION OF SUPEROXIDE BY CA2+ - AN ALTERNATE MECHANISM FOR THE CARDIOTOXICITY OF DOXORUBICIN
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DOI：
10.1016/0041-008x(91)90336-d
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发表时间：
1991-01-01
影响因子：
3.8
通讯作者：
ACOSTA, D
中科院分区：
文献类型：
--
作者：
CHACON, E;ACOSTA, D
线粒体Ca ~（2+）积累和活性氧的形成是依赖于电子传递系统的过程。用EGTA螯合线粒体外Ca ~（2+）或钌红阻断线粒体Ca ~（2+）摄取，均可降低呼吸大鼠心肌线粒体产生超氧化物。多柔比星的线粒体实验显示增强的活性氧刺激，这也被EGTA或钌红抑制。用阿霉素处理的心肌细胞培养物显示细胞内活性氧的形成增强，这先于细胞损伤。钌红不仅减弱了细胞内活性氧的形成，而且还增加了细胞活力。线粒体Ca 2+转运和超氧化物形成之间的关系表明，阿霉素对线粒体Ca 2+稳态的破坏可能与活性氧的释放及其心脏毒性有关。
Mitochondrial Ca2+accumulation and the formation of reactive oxygen species are processes dependent on the electron transport system. The production of superoxide by respiring rat heart mitochondria was decreased by either chelating extramitochondrial Ca2+with EGTA or by blocking mitochondrial Ca2+uptake with ruthenium red. Mitochondrial experiments with doxorubicin showed an enhanced stimulation of reactive oxygen species, which was also inhibited by EGTA or ruthenium red. Myocardial cell cultures treated with doxorubicin showed an enhanced formation of intracellular reactive oxygen species, which preceded cell damage. Ruthenium red not only attenuated the enhanced formation of intracellular reactive oxygen species, but also increased cell viability. The relationship between mitochondrial Ca2+transport and the formation of superoxide suggests that a disruption in mitochondrial Ca2+homeostasis by doxorubicin may be involved in the release of reactive oxygen species and its cardiotoxicity.