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

骨骼肌具有高度的适应性，可以响应生理刺激改变其结构和功能特性。由于各种条件，如抗阻运动和功能超负荷，增加肌肉活动，诱导骨骼肌肥大和肌纤维型转化为缓慢的轮廓。另一方面，肌肉不活动，如卧床休息、固定和微重力时可能发生的，与肌肉萎缩和纤维型向快速轮廓转变有关。在这个项目期间，我们已经在分子水平上展示了一些过程。以下是一些分析的例子，但这个空间太小，无法总结所有的研究成果，因此，请参阅参考文献和论文版的闭幕项目报告。钙调神经磷酸酶（CaN）信号通路已被牵连在慢肌纤维基因的转录调控和肌肉肥大。调查的功能作用 关于我们 CaN作为肌肉生长和/或肌纤维类型的调节剂，在从不活动恢复的条件下，ICR小鼠用于检查后肢悬吊（HS）和再负荷对骨骼肌纤维大小和肌纤维类型的影响。出乎意料的是，我们观察到的CaN及其下游效应器的蛋白质含量增加HS后，虽然肌纤维类型向一个快速的配置文件和明显的肌肉萎缩是induced.It是公认的耐力运动增加的过氧化物酶体增殖物激活受体γ辅激活因子-1 α（PGC-1 α），它控制的氧化代谢酶的表达。先前的报告表明，骨骼肌中线粒体蛋白表达的调节对冷暴露的反应取决于肌纤维类型。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-1 α表达的增加在快型肌肉中高于慢型肌肉。从结果来看，耐力运动引起PGC-1 α的增加，但增加的程度是肌肉类型特异性的。因此，PGC-1 α表达的增加不是耐力运动促进氧化能力的唯一因素。另一方面，我们通过肌球蛋白ATP酶染色分析了所有啮齿动物骨骼肌中慢肌纤维的全身分布，发现只有7个后肢骨骼肌中慢肌纤维非常丰富。此外，我们分析了人类骨骼肌基因表达的转录调控，以响应耐力训练。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