Isoflavones Derived from Soy Beans Prevent MuRF1-Mediated Muscle Atrophy in C2C12 Myotubes through SIRT1 Activation

DOI Web Site PubMed 被引用文献11件 参考文献25件 オープンアクセス
  • HIRASAKA Katsuya
    Department of Nutritional Physiology, Institute of Health Biosciences, the University of Tokushima Graduate School
  • MAEDA Tasuku
    Department of Nutritional Physiology, Institute of Health Biosciences, the University of Tokushima Graduate School
  • IKEDA Chika
    Department of Nutritional Physiology, Institute of Health Biosciences, the University of Tokushima Graduate School
  • HARUNA Marie
    Department of Nutritional Physiology, Institute of Health Biosciences, the University of Tokushima Graduate School
  • KOHNO Shohei
    Department of Nutritional Physiology, Institute of Health Biosciences, the University of Tokushima Graduate School
  • ABE Tomoki
    Department of Nutritional Physiology, Institute of Health Biosciences, the University of Tokushima Graduate School
  • OCHI Arisa
    Department of Nutritional Physiology, Institute of Health Biosciences, the University of Tokushima Graduate School
  • MUKAI Rie
    Department of Food Science, Institute of Health Biosciences, the University of Tokushima Graduate School
  • OARADA Motoko
    Medical Mycology Research Center, Chiba University
  • ESHIMA-KONDO Shigetada
    Department of Nutritional Physiology, Institute of Health Biosciences, the University of Tokushima Graduate School
  • OHNO Ayako
    Department of Nutritional Physiology, Institute of Health Biosciences, the University of Tokushima Graduate School
  • OKUMURA Yuushi
    Department of Nutritional Physiology, Institute of Health Biosciences, the University of Tokushima Graduate School
  • TERAO Junji
    Department of Food Science, Institute of Health Biosciences, the University of Tokushima Graduate School
  • NIKAWA Takeshi
    Department of Nutritional Physiology, Institute of Health Biosciences, the University of Tokushima Graduate School

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説明

Proinflammatory cytokines are factors that induce ubiquitin-proteasome-dependent proteolysis in skeletal muscle, causing muscle atrophy. Although isoflavones, as potent antioxidative nutrients, have been known to reduce muscle damage during the catabolic state, the non-antioxidant effects of isoflavones against muscle atrophy are not well known. Here we report on the inhibitory effects of isoflavones such as genistein and daidzein on muscle atrophy caused by tumor necrosis factor (TNF)-α treatment. In C2C12 myotubes, TNF-α treatment markedly elevated the expression of the muscle-specific ubiquitin ligase MuRF1, but not of atrogin-1, leading to myotube atrophy. We found that MuRF1 promoter activity was mediated by acetylation of p65, a subunit of NFκB, a downstream target of the TNF-α signaling pathway; increased MuRF1 promoter activity was abolished by SIRT1, which is associated with deacetylation of p65. Of interest, isoflavones induced expression of SIRT1 mRNA and phosphorylation of AMP kinase, which is well known to stimulate SIRT1 expression, although there was no direct effect on SIRT1 activation. Moreover, isoflavones significantly suppressed MuRF1 promoter activity and myotube atrophy induced by TNF-α in C2C12 myotubes. These results suggest that isoflavones suppress myotube atrophy in skeletal muscle cells through activation of SIRT1 signaling. Thus, the efficacy of isoflavones could provide a novel therapeutic approach against inflammation-related muscle atrophy.

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