| Research Abstract |
To investigate the role of the calcineurin in development of slow muscle fibers, we first compared the mRNA expression of genes in the calcineurin signaling pathway in slow muscle fibers with that in fast muscle fibers. It revealed that the mRNA expression of myocyte specific calcineurin inhibitory protein 1 (MCIP1) was at least 10 times higher in slow muscle fibers than in fast muscle fibers. The difference in the MCIP1 mRNA expression was lost, when slow and fast muscle fibers lost their differentiated phenotypes after denervation of skeletal muscles.
The expression of MCIP1 mRNA was transiently induced in skeletal muscles within 4 hours after acute exercise. In the MCIP1 promoter sequence, there is an array of tentative NFAT binding sites, which might respond to the calcineurin activity. Indeed, calcineurin directly regulated the MCIP1 promoter via these NFAT binding sites. Therefore, the expression levels of MCIP1 mRNA might directly reflect the calcineurin activity in skeletal muscle, which is otherwise very difficult to monitor in vivo.
We next examined the relationship between the intensity of acute exercise and the induction of MCIP1 mRNA in rat skeletal muscles, after treadmill running at various speed and time. The expression of MCIP1 mRNA was proportionally correlated with the intensity of acute exercise, and it was induced by very mild exercise (12 m/min for 10 min). Even when varying speed from 8〜16 m/min for 120 m, the MCIP1 mRNA was equally induced in rat skeletal muscles. These results suggest that the expression level of MCIP1 mRNA is a good indicator of the calcineurin activity in skeletal muscle, and even very mild exercise is enough to activate the calcineurin signaling pathway, which is important for development and maintenance of slow muscle fibers.
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