Impaired mitochondrial oxidative phosphorylation in skeletal muscle of the dystrophin-deficient mdx mouse
Impaired mitochondrial oxidative phosphorylation in skeletal muscle of the dystrophin-deficient mdx mouse
复制标题
DOI：
10.1023/a:1006868130002
复制
发表时间：
1998-06-01
影响因子：
4.3
通讯作者：
Kunz, WS
中科院分区：
文献类型：
--
作者：
Kuznetsov, AV;Winkler, K;Kunz, WS
mdx小鼠是杜氏肌营养不良症的动物模型，用于研究与肌营养不良蛋白缺乏相关的线粒体功能变化。骨骼肌的酶分析显示，与对照组相比，成年mdx小鼠四头肌中所有呼吸链相关酶的活性降低约50%，而在心肌中未观察到差异。心肌和骨骼肌中细胞溶质和线粒体基质酶的活性与对照值无显著差异。在皂苷渗透的mdx小鼠骨骼肌纤维中，线粒体呼吸的最大速率比对照组低约两倍。这些变化也表现在分离的线粒体水平上。Mdx小鼠肌线粒体最大呼吸活性仅为对照小鼠骨骼肌线粒体的60%，线粒体内膜血红素蛋白含量仅为对照小鼠骨骼肌线粒体的60%左右。在杜氏肌营养不良症患者的骨骼肌活检中观察到类似的结果。这些数据强烈表明，所有线粒体内膜酶的量的特定减少，最有可能是由于肌纤维的Ca2+过载，是肌营养不良蛋白缺乏的骨骼肌中的生物能缺陷的原因。
The mdx mouse, an animal model of the Duchenne muscular dystrophy, was used for the investigation of changes in mitochondrial function associated with dystrophin deficiency. Enzymatic analysis of skeletal muscle showed an approximately 50% decrease in the activity of all respiratory chain-linked enzymes in musculus quadriceps of adult mdx mice as compared with controls, while in cardiac muscle no difference was observed. The activities of cytosolic and mitochondrial matrix enzymes were not significantly different from the control values in both cardiac and skeletal muscles. In saponin-permeabilized skeletal muscle fibers of mdx mice the maximal rates of mitochondrial respiration were about two times lower than those of controls. These changes were also demonstrated on the level of isolated mitochondria. Mdx muscle mitochondria had only 60% of maximal respiration activities of control mice skeletal muscle mitochondria and contained only about 60% of hemoproteins of mitochondrial inner membrane. Similar findings were observed in a skeletal muscle biopsy of a Duchenne muscular dystrophy patient. These data strongly suggest that a specific decrease in the amount of all mitochondrial inner membrane enzymes, most probably as result of Ca2+ overload of muscle fibers, is the reason for the bioenergetic deficits in dystrophin-deficient skeletal muscle.