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Leucine induces myofibrillar protein accretion in cultured skeletal muscle through m TOR dependent and ‐independent control of myosin heavy chain m RNA levels
Author(s) -
Haegens Astrid,
Schols Annemie M.,
van Essen A L.,
van Loon Luc J.,
Langen Ramon C.
Publication year - 2012
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201100695
Subject(s) - myofibril , myosin , leucine , skeletal muscle , biology , myosin light chain kinase , protein biosynthesis , myocyte , biochemistry , chemistry , amino acid , microbiology and biotechnology , endocrinology
Scope Nutritional intervention during muscle wasting aims to attenuate net muscle protein loss. Branched chain amino acids, especially leucine, are able to stimulate the anabolic mammalian target of rapamycin (m TOR ) signalling cascade and protein synthesis. It has been suggested that muscle myofibrillar protein expression is more responsive to amino acid supplementation compared to cytoplasmic proteins, although accretion of myofibrillar proteins has not extensively been investigated. We hypothesized that leucine specifically increases myofibrillar protein synthesis in skeletal muscle. Methods and results This hypothesis was investigated in C 2 C 12 skeletal muscle cells using physiologically relevant culture conditions. Leucine supplementation specifically increased myofibrillar protein accretion, including myosin heavy chain‐slow and ‐fast and myosin light chain 1 and ‐3 in C 2 C 12 cells. Neither total protein content, nor de novo protein synthesis was affected, despite leucine‐induced increased 4 E ‐ BP 1 and S 6 K 1 phosphorylation. Leucine supplementation did not affect myogenesis, measured by creatine kinase activity and myoblast fusion, either. Remarkably, leucine‐induced increased myofibrillar protein accretion was accompanied by elevated M y HC m RNA levels, which involved m TOR ‐dependent and ‐independent regulation of M y HC ‐4 and M y HC ‐7 gene‐expression, respectively. Conclusion This study clearly demonstrates myofibrillar and not generic protein accretion in skeletal muscle following leucine supplementation, and suggests this involves pre‐translational control of M y HC expression by leucine.