Potato protein hydrolysate (PP902) inhibits dexamethasone-induced muscle atrophy by regulating MuRF1 and MAFbx expression in C2C12 myotubes in vitro #MMPMID41351257
Kumar KS; Chen YJ; Abomughaid MM; He YH; Lo YH; Chang CF; Mohammedsaleh ZM; Lin WT
J Sci Food Agric 2025[Dec]; ? (?): ? PMID41351257show ga
BACKGROUND: Skeletal muscle atrophy occurs when muscle mass and strength decrease due to aging, starvation, cancer, and cachectic diseases. Recently, an increasing focus has been on investigating potato protein's nutritional and functional properties and its wide-ranging applications. Steroids, especially glucocorticoids, have been extensively examined and found to cause muscle atrophy. Recently, we found that PP902 prevents hyperglycemia-induced muscle atrophy in cultured myotubes, although its impact on steroid-induced muscle atrophy remains unclear. Therefore, this study aimed to investigate if the potato peptide PP902 could prevent steroid-induced muscle atrophy in vitro. RESULTS: The MTT assay showed no cytotoxicity in C2C12 myotubes at a dosage of 200 mug mL(-1). To study the anti-atrophic effects of PP902 on muscle cell atrophy, C2C12 myotubes were treated with 100 mumol L(-1) dexamethasone (DEX) and/or 100 mug mL(-1) PP902 for 24 h. DEX-treated cells showed reduced myotube diameter compared to control cells, while PP902 administration prevented muscular atrophy. Next, western blot analysis and reverse transcription quantitative polymerase chain reaction were used to measure MAFbx and MuRF1 protein and mRNA levels, respectively. Results showed that PP902 dramatically decreased MAFbx and MuRF1 expression. Additionally, PP902 treatment in C2C12 cells produced a dose-dependent increase in myosin heavy chain (MHC) and a decrease in phosphorylated myosin heavy chain (p-MHC), which is a key player in skeletal myogenesis. Furthermore, DEX treatment significantly increased the expression of glucocorticoid receptor alpha (GRalpha), whereas low-dose PP902 (12.5, 15, and 50 mug mL(-1)) failed to prevent GRalpha activation. PP902 (100 mug mL(-1)) suppresses GRalpha activity only at higher concentrations. Additional investigations revealed that PP902 supplementation reduced DEX-induced FOXO1 activity and enhanced p-FoxO1 and Akt activation. CONCLUSION: Taken together, this study indicates that PP902 inhibits MAFbx and MuRF1 expression associated with inhibiting FoxO1 in C2C12 cells, potentially useful for developing anti-atrophy functional foods. (c) 2025 Society of Chemical Industry.
J+Sci+Food+Agric 2025 ; ? (?): ?
