The collagen derived dipeptide hydroxyprolyl-glycine promotes C2C12 myoblast differentiation and myotube hypertrophy

Aug 25, 2016Biochemical and biophysical research communications

The collagen-derived molecule hydroxyprolyl-glycine supports muscle cell growth and enlargement

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Abstract

Hydroxyprolyl-glycine (Hyp-Gly) increased the fusion index and myotube size in murine skeletal muscle C2C12 cells.

Hyp-Gly enhances the expression of myotube-specific proteins, including myosin heavy chain (MyHC) and tropomyosin.
Phosphorylation of Akt, mTOR, and p70S6K is increased in myoblasts by Hyp-Gly.
Inhibition of phosphatidylinositol 3-kinase (PI3K) reduces Hyp-Gly's effects on protein phosphorylation.
The peptide/histidine transporter 1 (PHT1) is highly expressed in myoblasts and myotubes.
Co-administration of histidine inhibits Hyp-Gly-induced phosphorylation of p70S6K in muscle cells.

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The majority of studies on possible roles for collagen hydrolysates in human health have focused on their effects on bone and skin. Hydroxyprolyl-glycine (Hyp-Gly) was recently identified as a novel collagen hydrolysate-derived dipeptide in human blood. However, any possible health benefits of Hyp-Gly remain unclear. Here, we report the effects of Hyp-Gly on differentiation and hypertrophy of murine skeletal muscle C2C12 cells. Hyp-Gly increased the fusion index, the myotube size, and the expression of the myotube-specific myosin heavy chain (MyHC) and tropomyosin structural proteins. Hyp-Gly increased the phosphorylation of Akt, mTOR, and p70S6K in myoblasts, whereas the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 inhibited their phosphorylation by Hyp-Gly. LY294002 and the mammalian target of rapamycin (mTOR) inhibitor rapamycin repressed the enhancing effects of Hyp-Gly on MyHC and tropomyosin expression. The peptide/histidine transporter 1 (PHT1) was highly expressed in both myoblasts and myotubes, and co-administration of histidine inhibited Hyp-Gly-induced phosphorylation of p70S6K in myoblasts and myotubes. These results indicate that Hyp-Gly can induce myogenic differentiation and myotube hypertrophy and suggest that Hyp-Gly promotes myogenic differentiation by activating the PI3K/Akt/mTOR signaling pathway, perhaps depending on PHT1 for entry into cells.

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The collagen derived dipeptide hydroxyprolyl-glycine promotes C2C12 myoblast differentiation and myotube hypertrophy

Abstract

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