Impaired voluntary running capacity of creatine kinase-deficient mice
Impaired voluntary running capacity of creatine kinase-deficient mice
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DOI：
10.1113/jphysiol.2005.086397
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发表时间：
2005-06-15
影响因子：
5.5
通讯作者：
Ventura-Clapier, R
中科院分区：
文献类型：
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作者：
Momken, I;Lechêne, P;Ventura-Clapier, R
肌酸激酶系统(CK)在骨骼肌和心肌的能量传递中起着重要作用。该酶的两种主要亚型，胞质MM-CK和线粒体MI-CK，以发育和肌肉类型特异的方式表达。缺乏这两种亚型中的一种或两种的小鼠可以存活和生育，但表现出深刻的功能、代谢和结构性肌肉重构，主要影响快速骨骼肌，这表明氧化代谢对收缩功能的贡献增加。然而，这些变化在体能方面的后果尚未确定。因此，我们比较了9月龄雄性野生型(WT)、M-CK基因敲除(M-CK-/-)和M-CK和mi-CK双基因敲除(CK-/-)小鼠的自愿运动能力。CK-/-小鼠的运动成绩(以总距离和训练期间完成的工作量计算)比对照组低10倍以上，M-CK-/-小鼠表现中等。同样，M-CK-/-小鼠每次激活的平均距离较低，CK-/-小鼠甚至更低。然而，最大跑速度(V-max)仅对CK-/-小鼠较低。这伴随着CK-/-小鼠严重的骨骼肌质量下降，并有组织学损伤的迹象，包括间质面积扩大，间质中单个核细胞聚集，肌纤维大小不均，以及存在非常小的纤维。在多巴酚丁胺刺激过程中，磁共振成像没有观察到明显的心功能障碍迹象。这些结果表明，CK缺乏导致的代谢衰竭深刻地影响了小鼠进行慢性耐力跑运动的能力，这种表现的下降也与肌肉萎缩有关。
The creatine kinase system (CK) is important for energy delivery in skeletal and cardiac muscles. The two main isoforms of this enzyme, cytosolic MM-CK and mitochondrial mi-CK, are expressed in a developmental and muscle-type specific manner. Mice deficient in one or both of these isoforms are viable and fertile but exhibit profound functional, metabolic and structural muscle remodelling that primarily affects fast skeletal muscles, which show an increased contribution of oxidative metabolism to contractile function. However, the consequences of these alterations in terms of physical capabilities have not yet been characterized. Consequently, we compared the voluntary exercise capacity of 9-month-old male wild-type (WT), M-CK knockout (M-CK-/-), and M-CK and mi-CK double knockout (CK-/-) mice, using cages equipped with running wheels. Exercise performance, calculated by total distance covered and by work done during the training period, was more than 10-fold lower in CK-/- mice than controls, with M-CK-/- mice exhibiting intermediate performance. Similarly, the mean distance run per activation was lower in M-CK-/- and even lower in CK-/- mice. However, the maximal running speed (V-max) was lower only for CK-/- mice. This was accompanied by severe skeletal muscle mass decrease in CK-/- mice, with signs of histological damage that included enlarged interstitial areas, aggregations of mononuclear cells in the interstitium, heterogeneity of myofibre size and the presence of very small fibres. No overt sign of cardiac dysfunction was observed by magnetic resonance imaging during dobutamine stimulation. These results show that metabolic failure induced by CK deficiency profoundly affects the ability of mice to engage in chronic bouts of endurance running exercise and that this decrease in performance is also associated with muscle wasting.