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Discrepancy between increased mTORC1 signaling and total muscle protein accretion after leucine stimulation
Author(s) -
Haegens Astrid,
Schols Annemie M,
Essen A LM,
Loon Luc JC,
Langen Ramon C
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.989.22
Subject(s) - mtorc1 , leucine , p70 s6 kinase 1 , amino acid , ribosomal protein s6 , western blot , pi3k/akt/mtor pathway , myocyte , chemistry , stimulation , endocrinology , medicine , biology , biochemistry , microbiology and biotechnology , signal transduction , gene
An important goal of nutritional intervention in muscle wasting disorders is to stimulate protein synthesis. The branched chain amino acids (BCAA), and leucine in particular have been suggested to promote protein synthesis via activation of the mammalian target of rapamycin (mTOR) pathway. The endpoints determined so far were mostly cell signaling parameters leaving the question open whether the activation of mTORC1 by leucine leads to protein accretion? The aim of this study was to investigate, in C2C12 cells cultured in the presence of physiological AA levels, whether the stimulating effects of leucine on mTORC1 lead to total and muscle specific protein accretion. Myoblasts were differentiated in DMEM diluted with HBSS (supplemented with NaHCO 3 ) to yield culture medium containing glucose (1g/L), FBS (1%) and physiological AA levels (10% of unmodified DMEM) in presence or absence of 5mM leucine. Leucine stimulated the mTORC1 targets 4E‐BP1 and S6K1, measured by western blot. Creatine kinase activity and total protein accretion were not increased in cells that had differentiated in the presence of leucine for 5 days. Myosin Heavy Chain fast and slow, measured by western blot, were however increased under these conditions. These findings suggest a differential response of muscle proteins in the presence of leucine.