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Lactate increases myotube diameter via activation of MEK/ERK pathway in C2C12 cells
Author(s) -
Ohno Y.,
Oyama A.,
Kaneko H.,
Egawa T.,
Yokoyama S.,
Sugiura T.,
Ohira Y.,
Yoshioka T.,
Goto K.
Publication year - 2018
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.13042
Subject(s) - myogenesis , skeletal muscle , c2c12 , mapk/erk pathway , ribosomal s6 kinase , extracellular , kinase , myocyte , biology , protein kinase a , medicine , endocrinology , protein kinase b , chemistry , phosphorylation , microbiology and biotechnology , p70 s6 kinase 1
Aim Lactate is produced in and released from skeletal muscle cells. Lactate receptor, G‐protein‐coupled receptor 81 (GPR81), is expressed in skeletal muscle cells. However, a physiological role of extracellular lactate on skeletal muscle is not fully clarified. The purpose of this study was to investigate extracellular lactate‐associated morphological changes and intracellular signals in C2C12 skeletal muscle cells. Methods Mouse myoblast C2C12 cells were differentiated for 5 days to form myotubes. Sodium lactate (lactate) or GPR81 agonist, 3,5‐dihydroxybenzoic acid (3,5‐DHBA), was administered to the differentiation medium. Results Lactate administration increased the diameter of C2C12 myotubes in a dose‐dependent manner. Administration of 3,5‐DHBA also increased myotube diameter. Not only lactate but also 3,5‐DHBA upregulated the phosphorylation level of mitogen‐activated protein kinase kinase 1/2 (MEK1/2), p42/44 extracellular signal‐regulated kinase‐1/2 (ERK1/2) and p90 ribosomal S6 kinase (p90RSK). MEK inhibitor U0126 depressed the phosphorylation of ERK‐p90RSK and increase in myotube diameter induced by lactate. On the other hand, both lactate and 3,5‐DHBA failed to induce significant responses in the phosphorylation level of Akt, mammalian target of rapamycin, p70 S6 kinase and protein degradation‐related signals. Conclusion These observations suggest that lactate‐associated increase in the diameter of C2C12 myotubes is induced via activation of GRP81‐mediated MEK/ERK pathway. Extracellular lactate might have a positive effect on skeletal muscle size.