Hughes S M, Chi M M, Lowry O H, Gundersen K
The Randall Institute, King's College London, London WC2B 5RL, United Kingdom.
J Cell Biol. 1999 May 3;145(3):633-42. doi: 10.1083/jcb.145.3.633.
Physical training regulates muscle metabolic and contractile properties by altering gene expression. Electrical activity evoked in muscle fiber membrane during physical activity is crucial for such regulation, but the subsequent intracellular pathway is virtually unmapped. Here we investigate the ability of myogenin, a muscle-specific transcription factor strongly regulated by electrical activity, to alter muscle phenotype. Myogenin was overexpressed in transgenic mice using regulatory elements that confer strong expression confined to differentiated post-mitotic fast muscle fibers. In fast muscles from such mice, the activity levels of oxidative mitochondrial enzymes were elevated two- to threefold, whereas levels of glycolytic enzymes were reduced to levels 0.3-0.6 times those found in wild-type mice. Histochemical analysis shows widespread increases in mitochondrial components and glycogen accumulation. The changes in enzyme content were accompanied by a reduction in fiber size, such that many fibers acquired a size typical of oxidative fibers. No change in fiber type-specific myosin heavy chain isoform expression was observed. Changes in metabolic properties without changes in myosins are observed after moderate endurance training in mammals, including humans. Our data suggest that myogenin regulated by electrical activity may mediate effects of physical training on metabolic capacity in muscle.
体育锻炼通过改变基因表达来调节肌肉的代谢和收缩特性。体育活动期间在肌纤维膜中诱发的电活动对于这种调节至关重要，但随后的细胞内信号通路几乎尚未明确。在这里，我们研究了肌细胞生成素（一种受电活动强烈调节的肌肉特异性转录因子）改变肌肉表型的能力。使用赋予仅限于分化后的有丝分裂后快速肌纤维强表达的调控元件，在转基因小鼠中过表达肌细胞生成素。在这些小鼠的快肌中，氧化型线粒体酶的活性水平提高了两到三倍，而糖酵解酶的水平降低到野生型小鼠中发现水平的0.3 - 0.6倍。组织化学分析显示线粒体成分和糖原积累普遍增加。酶含量的变化伴随着纤维大小的减小，使得许多纤维获得了氧化型纤维典型的大小。未观察到纤维类型特异性肌球蛋白重链同工型表达的变化。在包括人类在内的哺乳动物进行适度耐力训练后，观察到代谢特性发生变化而肌球蛋白未发生变化。我们的数据表明，受电活动调节的肌细胞生成素可能介导体育锻炼对肌肉代谢能力的影响。
