| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Research Abstract |
Proinflammatory cytokines are factors that induce ubiquitin-proteasome-dependent proteolysis in skeletal muscle, causing age-related muscle atrophy. However, a molecular mechanism of muscle atrophy caused by aging remains unclear. In the present study, we examined the role of ubiquitin-proteasome-dependent proteolysis on aging. In C2C12 myotubes, TNF-alpha treatment markedly elevated the expression of the muscle-specific ubiquitin ligase MuRF1, leading to myotube atrophy. We found that MuRF1 promoter activity was mediated by acetylation of p65, a subunit of NFkB, a downstream target of the TNF-alpha signaling pathway. In addition, the acetylation of p65 was observed in skeletal muscle of aged mice. Interestingly, we found that MuRF1 deficient mice were resistant to aged-related muscle atrophy. Thus, the inhibition of NFkB-MuRF1 signaling by deacetylation could provide a novel therapeutic approach against age-related muscle atrophy.
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