期刊
NUTRITION RESEARCH
卷 34, 期 4, 页码 368-374出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.nutres.2014.02.003
关键词
beta-Hydroxy-beta-methylbutyrate; Phosphoinositide 3-kinase; Ubiquitin ligase; Forkhead box class 0; C2C12
资金
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [223900143, 25670349]
- Grants-in-Aid for Scientific Research [25670349, 24659385, 22390143] Funding Source: KAKEN
beta-Hydroxy-beta-methylbutyrate (HMB) prevents deleterious muscle responses under pathological conditions, including tumor- and chronic steroid therapy-related muscle losses. Here, we investigated the hypothesis that HMB may modulate the balance between protein synthesis and degradation in the PI3K1Akt-mediated mammalian target of rapamycin (mTOR) and FoxO1/FoxO3a-dependent mechanisms in differentiated C2C12 muscle cells. We also tested the effect of HMB on the expression of MuRF-1 and atrogin-1 in response to the inflammatory stress. beta-Hydroxy-beta-methylbutyrate up-regulated phosphorylation of Akt and mTOR, and these effects were completely abolished in the presence of PI3K inhibitor LY294002. beta-Hydroxy-beta-methylbutyrate also up-regulated FoxO1 and FoxO3a phosphorylation, and these changes were inhibited by LY294002. Although, unexpectedly, HMB failed to reduce the expressions of atrophy-related atrogin-1 messenger RNA and the protein response to the proinflammatory cytokines tumor necrosis factor alpha plus interferon gamma,HMB did attenuate the MuRF-1 expression. Thus, HMB appears to restore the balance between intracellular protein synthesis and proteolysis, likely via activation of the PI3K/Akt-dependent mTOR and FoxO1/ FoxO3a signaling pathway and the reduction of tumor necrosis factor a/interferon y-induced MuRF-1 expression, thereby ameliorating aging-related muscle atrophy. (C) 2014 Elsevier Inc. All rights reserved.
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