期刊
ACTA PHYSIOLOGICA
卷 223, 期 2, 页码 -出版社
WILEY
DOI: 10.1111/apha.13042
关键词
lactate; p42; 44 extracellular signal-regulated kinase-1; 2; skeletal muscle cells
类别
资金
- Japan Society for the Promotion of Science [16K12942, 16K13022, 17K01762]
- Promotion and Mutual Aid Corporation for Private Schools of Japan
- Naito Foundation
- Descente Sports Foundation
- Uehara Memorial Foundation
- Toyohashi SOZO University
- Japan Coffee Association
- Grants-in-Aid for Scientific Research [16K16450, 16K12942, 17K01762, 16K13022] Funding Source: KAKEN
AimLactate 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. MethodsMouse myoblast C2C12 cells were differentiated for 5days to form myotubes. Sodium lactate (lactate) or GPR81 agonist, 3,5-dihydroxybenzoic acid (3,5-DHBA), was administered to the differentiation medium. ResultsLactate 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. ConclusionThese 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.
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