Abstract Sepsis and lipopolysaccharide (LPS) may decrease skeletal muscle protein synthesis by impairing mTOR (mammalian target of rapamycin) activity. The role of mTOR in regulating muscle protein synthesis was assessed in wild-type (WT) and mTOR heterozygous (+/−) mice under basal conditions and in response to LPS and/or leucine stimulation. No difference in body weight of mTOR +/− mice was observed compared with WT mice; whereas whole body lean body mass was reduced. Gastrocnemius weight was decreased in mTOR +/− mice, which was attributable in part to a reduced rate of basal protein synthesis. LPS decreased muscle protein synthesis in WT and mTOR +/− mice to the same extent. Reduced muscle protein synthesis in mTOR +/− mice under basal and LPS-stimulated conditions was associated with lower 4E-BP1 and S6K1 phosphorylation. LPS also decreased PRAS40 phosphorylation and increased phosphorylation of raptor and IRS-1 (Ser 307 ) to the same extent in WT and mTOR +/− mice. Muscle atrogin-1 and MuRF1 mRNA content was elevated in mTOR +/− mice under basal conditions, implying increased ubiquitin-proteasome-mediated proteolysis, but the LPS-induced increase in these atrogenes was comparable between groups. Plasma insulin and IGF-I as well as tissue expression of TNFα, IL-6, or NOS2 did not differ between WT and mTOR +/− mice. Finally, whereas LPS impaired the ability of leucine to stimulate muscle protein synthesis and 4E-BP1 phosphorylation in WT mice, this inflammatory state rendered mTOR +/− mice leucine unresponsive. These data support the idea that the LPS-induced reduction in mTOR activity is relatively more important in regulating skeletal muscle mass in response to nutrient stimulation than under basal conditions. mammalian target of rapamycin endotoxin protein synthesis eukarotic initiation factor 4E-binding protein-1 ribosomal protein S6 kinase-1 leucine Copyright © 2010 the American Physiological Society
End of preview. The entire article is 13 pages. To view the full-text, please rent this article to continue.
/lp/the-american-physiological-society/skeletal-muscle-protein-balance-in-mtor-heterozygous-mice-in-response-0vB6XRcb9b
Welcome to DeepDyve! Rent Premier Research Articles and Save Up to 90%
Skeletal muscle protein balance in mTOR heterozygous mice in response to inflammation and leucine
Lang, Charles H.; Frost, Robert A.; Bronson, Sarah K.; Lynch, Christopher J.; Vary, Thomas C.
Follow AJP - Endocrinology and Metabolism
, Volume 298 (6): E1283
The American Physiological Society – Jun 1, 2010
More Info
More Like This Article
View All dataSource[]=actageo&dataSource[]=aspet&dataSource[]=aaos&dataSource[]=aacc&dataSource[]=aacr&dataSource[]=aea&dataSource[]=aip&dataSource[]=ajnr&dataSource[]=ams&dataSource[]=aps_physical&dataSource[]=appi_book&dataSource[]=appi_journal&dataSource[]=apha&dataSource[]=asip&dataSource[]=asm&dataSource[]=asn&dataSource[]=aspb&dataSource[]=avs&dataSource[]=annual_reviews&dataSource[]=arxiv&dataSource[]=acm&dataSource[]=berghahn&dataSource[]=cabi&dataSource[]=clinical_trials&dataSource[]=dailymed&dataSource[]=degruyter&dataSource[]=du_press&dataSource[]=esa&dataSource[]=eu_press&dataSource[]=elsevier&dataSource[]=emerald&dataSource[]=ejtr&dataSource[]=emea&dataSource[]=epo&dataSource[]=faseb&dataSource[]=gsa&dataSource[]=health_affairs&dataSource[]=hindawi&dataSource[]=imanager&dataSource[]=imedpub&dataSource[]=informa_healthcare&dataSource[]=informs&dataSource[]=iop&dataSource[]=iucr&dataSource[]=iospress&dataSource[]=jbjs&dataSource[]=leftcoast&dataSource[]=lu_press&dataSource[]=mesharpe&dataSource[]=mary_ann_liebert&dataSource[]=medline&dataSource[]=mit_press&dataSource[]=nature&dataSource[]=oxford&dataSource[]=pier_professional&dataSource[]=pnas&dataSource[]=portlandpress&dataSource[]=psyc_articles&dataSource[]=psyc_books&dataSource[]=psyc_critiques&dataSource[]=plos_journal&dataSource[]=pubmed_central&dataSource[]=rsna&dataSource[]=rockefeller&dataSource[]=rcn&dataSource[]=ria&dataSource[]=rsc&dataSource[]=sage&dataSource[]=spie&dataSource[]=springer_journal&dataSource[]=springer&dataSource[]=taylor_francis&dataSource[]=aps&dataSource[]=the_scientist&dataSource[]=uc_press&dataSource[]=uspto_abstract&dataSource[]=wiley&dataSource[]=pct
© 2012 DeepDyve, Inc. All rights reserved.
Terms of Service | Privacy Policy
