Studies on gene expression concerning exercise-induced differentiation or metabolic change in skeletal muscle

骨骼肌具有很强的适应性，可以根据生理刺激改变其结构和功能特性。由于抵抗运动和功能超负荷等各种条件引起的肌肉活动增加，导致骨骼肌肥大和肌肉纤维型转变为缓慢的轮廓。另一方面，像卧床休息、制动和微重力一样，肌肉不活动与肌肉萎缩和纤维类型向快速方向转变有关。在这个项目期间，我们已经在分子水平上演示了一些过程。以下是一些分析的例子，但这一篇幅太小，不能总结所有的研究结果，因此，请参考参考文献和结题报告的纸质版本。钙调神经磷酸酶(CaN)信号通路与慢肌纤维基因的转录调控和肌肉肥大有关。研究…的功能作用作为肌肉生长和/或肌纤维类型的调节者，ICR小鼠在从静止状态恢复的条件下，观察后肢悬吊(HS)和再负荷对骨骼肌肌纤维大小和肌纤维类型的影响。我们意外地观察到HS后CaN及其下游效应物的蛋白质含量增加，尽管肌肉纤维类型转变为快速轮廓，并导致明显的肌肉萎缩。人们普遍认为，耐力运动增加了控制氧化代谢酶表达的过氧化物酶体增殖物激活受体γ辅活化子-1α(PGC-1α)的表达。以前的一份报告表明，骨骼肌对冷暴露的线粒体蛋白表达的调节依赖于肌肉纤维类型。由于冷暴露和耐力运动都是需要调整线粒体能量代谢的代谢挑战，我们假设运动诱导的氧化酶和PGC-1α在快型肌肉中的表达高于慢型肌肉。从结果来看，耐力运动导致PGC-1α的增加，但增加的程度是肌肉类型特有的。因此，PGC-1α表达的增加并不是耐力运动提高氧化能力的唯一因素。另一方面，我们用肌球蛋白ATPase染色分析了慢肌纤维在所有啮齿动物骨骼肌中的系统分布，发现只有7只后肢骨骼肌极富含慢肌纤维。此外，我们还分析了耐力训练对人体骨骼肌基因表达的转录调控。较少

Skeletal muscle is highly adaptable and can change its structural and functional properties in response to physiological stimuli. Increased muscle activity due to a variety of conditions, such as resistance exercise and functional overload, induces skeletal muscle hypertrophy and muscle fiber-type transformation toward a slow profile. On the other hand, muscle inactivity, as can occur with bed rest, immobilization, and microgravity, is associated with muscle atrophy and fiber-type transformation toward a fast profile. During this project period, we have demonstrated some of the processes at the molecular level. Followings are some examples of analyses, but this space is too small to summarize all the research results, therefore, please refer to the references and paper version of the closing project report.Calcineurin (CaN) signaling pathway has been implicated in the transcriptional regulation of slow muscle fiber genes and in muscle hypertrophy. To investigate the functional role of … More CaN as a regulator of muscle growth and/or muscle fiber type under conditions of recovery from inactivity, ICR mice were used for examining the effects of hindlimb suspension (HS) and reloading on skeletal muscle fiber size and muscle fiber type. Unexpectedly, we observed an increase in protein contents of CaN and its downstream effectors after HS, although the muscle fiber type transformed toward a fast profile and obvious muscle atrophy was induced.It is generally accepted that endurance exercise increases the expression of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha), which governs the expression of oxidative metabolic enzymes. A previous report demonstrated that the regulation of mitochondrial protein expression in skeletal muscles in response to cold exposure depends on muscle fibre type. Since cold exposure and endurance exercise are both metabolic challenges that require adjustments in mitochondrial energy metabolism, we hypothesized that the exercise-induced increase in oxidative enzymes and PGC-1alpha expression is higher in fast-type than in slow-type muscle. From the results, endurance exercise induced increase in PGC-1alpha, but the degree of increase was muscle type-specific. Therefore, the increase in PGC-1alpha expression is not the only factor that promotes oxidative capacity as a result of endurance exerciseOn the other hand, we analyzed the systemic distribution of slow muscle fibers in all rodent skeletal muscles by myosin ATPase staining and found that only seven hindlimb skeletal muscles were extremely rich in slow muscle fibers. Moreover, we analyzed transcription regulation of gene expression in human skeletal muscle in response to endurance training. Less