PMID- 27553280 OWN - NLM STAT- MEDLINE DCOM- 20170529 LR - 20211204 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 478 IP - 3 DP - 2016 Sep 23 TI - The collagen derived dipeptide hydroxyprolyl-glycine promotes C2C12 myoblast differentiation and myotube hypertrophy. PG - 1292-7 LID - S0006-291X(16)31378-X [pii] LID - 10.1016/j.bbrc.2016.08.114 [doi] AB - 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. CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. FAU - Kitakaze, Tomoya AU - Kitakaze T AD - Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 5998531, Japan. FAU - Sakamoto, Tomotaka AU - Sakamoto T AD - Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 5998531, Japan. FAU - Kitano, Takehiro AU - Kitano T AD - Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 5998531, Japan. FAU - Inoue, Naoki AU - Inoue N AD - Nitta Gelatin Inc., Peptide Division, 2-22 Futamata, Yao, Osaka, 5810024, Japan. FAU - Sugihara, Fumihito AU - Sugihara F AD - Nitta Gelatin Inc., Peptide Division, 2-22 Futamata, Yao, Osaka, 5810024, Japan. FAU - Harada, Naoki AU - Harada N AD - Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 5998531, Japan. FAU - Yamaji, Ryoichi AU - Yamaji R AD - Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 5998531, Japan. Electronic address: yamaji@biochem.osakafu-u.ac.jp. LA - eng PT - Journal Article DEP - 20160821 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Dipeptides) RN - 0 (Membrane Transport Proteins) RN - 0 (Slc15a4 protein, mouse) RN - 0 (Tropomyosin) RN - 0 (hydroxyprolyl-glycine) RN - 4QD397987E (Histidine) RN - 9007-34-5 (Collagen) RN - 97599-47-8 (peptide permease) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 3.6.4.1 (Myosin Heavy Chains) SB - IM MH - Animals MH - Cell Differentiation/*drug effects MH - Cell Size/drug effects MH - Collagen/*pharmacology MH - Dipeptides/*pharmacology MH - Histidine/pharmacology MH - Hypertrophy MH - Male MH - Membrane Transport Proteins/metabolism MH - Mice MH - Muscle Fibers, Skeletal/drug effects/metabolism/*pathology MH - Myoblasts/*cytology/drug effects/metabolism MH - Myosin Heavy Chains/metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Phosphorylation MH - Proto-Oncogene Proteins c-akt/metabolism MH - Ribosomal Protein S6 Kinases, 70-kDa/metabolism MH - Signal Transduction/drug effects MH - TOR Serine-Threonine Kinases/metabolism MH - Tropomyosin/metabolism OTO - NOTNLM OT - Collagen peptide OT - Differentiation OT - Hydroxyprolyl-glycine OT - Hypertrophy OT - Myoblast OT - Myotube EDAT- 2016/08/25 06:00 MHDA- 2017/05/30 06:00 CRDT- 2016/08/25 06:00 PHST- 2016/08/05 00:00 [received] PHST- 2016/08/19 00:00 [accepted] PHST- 2016/08/25 06:00 [entrez] PHST- 2016/08/25 06:00 [pubmed] PHST- 2017/05/30 06:00 [medline] AID - S0006-291X(16)31378-X [pii] AID - 10.1016/j.bbrc.2016.08.114 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2016 Sep 23;478(3):1292-7. doi: 10.1016/j.bbrc.2016.08.114. Epub 2016 Aug 21.