Lactate increases myotube diameter via activation of MEK/ERK pathway in C2C12 cells. (9th February 2018)

• Record Type: Journal Article
• Authors: Ohno, Y.; Oyama, A.; Kaneko, H.; Egawa, T.; Yokoyama, S.; Sugiura, T.; Ohira, Y.; Yoshioka, T.; Goto, K.
• Is Part Of: Acta physiologica. Volume 223:Number 2(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-02-09
• Subjects: lactate -- p42/44 extracellular signal‐regulated kinase‐1/2 -- skeletal muscle cells; Physiology -- Periodicals; Physiology -- Research -- Periodicals; 612
• DOI: 10.1111/apha.13042
• Languages: English
• ISSNs: 1748-1708

Abstract

Abstract: 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.