| Co-Investigator(Kenkyū-buntansha) |
KINUGASA Takashi University of Tsukuba, Graduate School of Comprehensive Human Sciences, Professor, 大学院人間総合科学研究科, 教授 (40110481)
OHNO Hideki Kyorin University, Department of Preventive Medicine and Public Health, Professor, 医学部, 教授 (00133819)
KASTUMURA Toshihito Tokyo Medical University, Department of Preventive Medicine and Public Health, Professor, 医学部, 教授 (80214352)
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| Research Abstract |
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
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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 exercise
On 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
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