PMID- 38002299 OWN - NLM STAT- MEDLINE DCOM- 20231127 LR - 20240104 IS - 2218-273X (Electronic) IS - 2218-273X (Linking) VI - 13 IP - 11 DP - 2023 Nov 5 TI - Preventive Effects of Collagen-Derived Dipeptide Prolyl-Hydroxyproline against Dexamethasone-Induced Muscle Atrophy in Mouse C2C12 Skeletal Myotubes. LID - 10.3390/biom13111617 [doi] LID - 1617 AB - Glucocorticoids, commonly used to manage inflammatory diseases, can induce muscle atrophy by accelerating the breakdown of muscle proteins. This research delves into the influence of Prolyl-hydroxyproline (Pro-Hyp), a collagen-derived peptide, on muscle atrophy induced with dexamethasone (DEX), a synthetic glucocorticoid, in mouse C2C12 skeletal myotubes. Exposure to DEX (10 muM) for 6 days resulted in a decrease in myotube diameter, along with elevated mRNA and protein levels of two muscle-atrophy-related ubiquitin ligases, muscle atrophy F-box (MAFbx, also known as atrogin-1) and muscle ring finger 1 (MuRF-1). Remarkably, treatment with 0.1 mM of Pro-Hyp mitigated the reduction in myotube thickness caused by DEX, while promoting the phosphorylation of Akt, mammalian target of rapamycin (mTOR), and forkhead box O3a (Foxo3a). This led to the inhibition of the upregulation of the ubiquitin ligases atrogin-1 and MuRF-1. These findings indicate the potential significance of Pro-Hyp as a promising therapeutic target for countering DEX-induced muscle atrophy. FAU - Kimira, Yoshifumi AU - Kimira Y AUID- ORCID: 0000-0001-5134-2519 AD - Department of Clinical Dietetics and Human Nutrition, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado-shi 350-0295, Japan. FAU - Osawa, Konosuke AU - Osawa K AD - Department of Clinical Dietetics and Human Nutrition, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado-shi 350-0295, Japan. FAU - Osawa, Yoshihiro AU - Osawa Y AD - Department of Clinical Dietetics and Human Nutrition, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado-shi 350-0295, Japan. FAU - Mano, Hiroshi AU - Mano H AD - Department of Clinical Dietetics and Human Nutrition, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado-shi 350-0295, Japan. LA - eng GR - 23K05095/Japan Society for the Promotion of Science/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20231105 PL - Switzerland TA - Biomolecules JT - Biomolecules JID - 101596414 RN - 0 (prolyl-4-hydroxyproline) RN - 7S5I7G3JQL (Dexamethasone) RN - 0 (Glucocorticoids) RN - 0 (Dipeptides) RN - EC 6.- (Ligases) RN - 0 (Ubiquitins) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) SB - IM MH - Mice MH - Animals MH - *Muscle, Skeletal/metabolism MH - *Dexamethasone/pharmacology/therapeutic use MH - Muscle Fibers, Skeletal/metabolism MH - Muscular Atrophy/chemically induced/drug therapy/prevention & control MH - Glucocorticoids/pharmacology/therapeutic use MH - Dipeptides/pharmacology MH - Ligases/metabolism MH - Ubiquitins/metabolism MH - Ubiquitin-Protein Ligases/metabolism MH - Mammals/metabolism PMC - PMC10669392 OTO - NOTNLM OT - Prolyl-hydroxyproline OT - collagen-derived peptide OT - mouse C2C12 skeletal myotubes OT - muscle atrophy OT - ubiquitin ligases COIS- The authors declare no conflict of interest. EDAT- 2023/11/25 12:42 MHDA- 2023/11/27 12:42 PMCR- 2023/11/05 CRDT- 2023/11/25 01:09 PHST- 2023/08/17 00:00 [received] PHST- 2023/11/02 00:00 [revised] PHST- 2023/11/03 00:00 [accepted] PHST- 2023/11/27 12:42 [medline] PHST- 2023/11/25 12:42 [pubmed] PHST- 2023/11/25 01:09 [entrez] PHST- 2023/11/05 00:00 [pmc-release] AID - biom13111617 [pii] AID - biomolecules-13-01617 [pii] AID - 10.3390/biom13111617 [doi] PST - epublish SO - Biomolecules. 2023 Nov 5;13(11):1617. doi: 10.3390/biom13111617.