Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-3-21
pubmed:abstractText
Mammalian target of rapamycin (mTOR) signaling is one of the main signaling pathways controlling protein synthesis. Leucine treatment upregulates mTOR signaling, which enhances protein synthesis; however, the mechanisms are not well understood. Herein, treatment of C2C12 myoblast cells with leucine enhanced the phosphorylation of mTOR and ribosomal protein S6 kinase. Leucine treatment also decreased the adenosine monophosphate/ATP ratio in myoblasts by 36.4 +/- 9.1% (P < 0.05) and reduced the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) alpha subunit at Thr172 (28.6 +/- 4.9% reduction, P < 0.05) and inhibited AMPK activity (43.6 +/- 3.5% reduction, P < 0.05). In addition, leucine increased the phosphorylation of mTOR at Ser2448 by 63.5 +/- 10.0% (P < 0.05) and protein synthesis by 30.6 +/- 6.1% (P < 0.05). Applying 5-aminoimidazole-4-carbox-amide 1-beta-d-ribonucleoside, an activator of AMPK, abolished the stimulation of mTOR signaling by leucine, showing that AMPK negatively controls mTOR signaling. To further show the role of AMPK in mTOR signaling, myoblasts expressing a dominant negative AMPKalpha subunit were employed. Negative myoblasts had very low AMPK activity. The activation of mTOR induced by leucine in these cells was abated, showing that AMPK contributed to mTOR activation. In conclusion, leucine stimulates mTOR signaling in part through AMPK inhibition. This study implicates AMPK as an important target for nutritional management to enhance mTOR signaling and protein synthesis in muscle cells, thereby increasing muscle growth.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/AICA ribonucleotide, http://linkedlifedata.com/resource/pubmed/chemical/AMP-Activated Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Aminoimidazole Carboxamide, http://linkedlifedata.com/resource/pubmed/chemical/Leucine, http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Ribonucleotides, http://linkedlifedata.com/resource/pubmed/chemical/Ribosomal Protein S6 Kinases, http://linkedlifedata.com/resource/pubmed/chemical/TOR Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/mTOR protein, mouse
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1525-3163
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
85
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
919-27
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:17178807-AMP-Activated Protein Kinases, pubmed-meshheading:17178807-Aminoimidazole Carboxamide, pubmed-meshheading:17178807-Animals, pubmed-meshheading:17178807-Cell Line, pubmed-meshheading:17178807-Enzyme Activation, pubmed-meshheading:17178807-Leucine, pubmed-meshheading:17178807-Mice, pubmed-meshheading:17178807-Multienzyme Complexes, pubmed-meshheading:17178807-Myoblasts, pubmed-meshheading:17178807-Phosphorylation, pubmed-meshheading:17178807-Protein Kinases, pubmed-meshheading:17178807-Protein-Serine-Threonine Kinases, pubmed-meshheading:17178807-Ribonucleotides, pubmed-meshheading:17178807-Ribosomal Protein S6 Kinases, pubmed-meshheading:17178807-Signal Transduction, pubmed-meshheading:17178807-TOR Serine-Threonine Kinases, pubmed-meshheading:17178807-Up-Regulation
pubmed:year
2007
pubmed:articleTitle
Leucine stimulates mammalian target of rapamycin signaling in C2C12 myoblasts in part through inhibition of adenosine monophosphate-activated protein kinase.
pubmed:affiliation
Department of Animal Science, University of Wyoming, Laramie 82071, USA. mindu@uwyo.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.