| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥2,600,000 (Direct Cost: ¥2,600,000)
|
|---|
| Research Abstract |
Skeletal muscles consist of slow-twitch and fast-twitch muscle fibers, which have distinct physiological and biochemical properties. The relative proportion of slow and fast muscle fibers is an important factor determining the contractile velocity and fatigability of skeletal muscle. To investigate the differentiation of muscle fibers, we first examine the composition of myofiber types in mice and rats skeletal muscles. It revealed that there was a group of skeletal muscles, which were extremely rich in slow muscle fibers and useful to study gene expression in slow muscle fibers.
Using cDNA prepared from the slow fiber-rich soleus muscle and the fast fiber-rich tibialis anterior muscle, we examined the gene expression profile by competitive hybridization to a DNA array (Agilent co ltd), and verified fiber-type specificity of differentially expressed genes by the cDNA panel prepared from 15 rat skeletal muscles, whose myofiber composition was determined. About more than 500 genes showed
… More
two-fold difference in their expression levels between the soleus and the tibialis anterior muscles. Seventy genes encode enzymes in metabolic pathways, such as glycolysis or lipolysis, 45 genes for structural proteins, 80 genes for transcription factors and/or signal transducers. Besides these known genes, we found the difference in 250 unknown genes between the soleus and the tibialis anterior muscles. To study the biological relevance of differential expression of these genes, we cut the tibialis and common peroneal nerves at the level of knee joints to induce muscle atrophy and dedifferentiation of myofibers. It has been postulated that denervation would induce slow to fast conversion of muscle fibers, thereby gene expression profiles of slow and fast muscle fibers become resembling. However, substantial difference remained between the soleus and tibialis anterior muscles one month after denervation. These results suggest that myofibers kept a part of gene expression profile specific to their original differentiation state, even loosing their nervous control. Less
|
