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Exercise preconditioning prevents immobilization-induced skeletal muscle atrophy by activating Prmt1-p38/ATF2-Sesn1 signaling axis in C57BL/6J mice

Year: 2025
Type: article
Abstract: This study aimed to explore the effects of a 10-week combined exercise regimen on immobilization-induced muscle atrophy and elucidate the possible function of Protein arginine methyltransferase 1 (Prmt1) in this process. 8-week-old male C57BL/6J mice were carried out combined exercise for 10 weeks. One week before the end of the intervention, mice underwent cast immobilization. Additionally, to investigate the potential mechanism in exercise-induced protection of skeletal muscle, mice in the exercise preconditioning group were administered TC-E−5003(an inhibitor of Prmt1 enzymatic activity). Exercise performance, muscle mass, and the cross-sectional area (CSA) of muscle fibers were analyzed. Besides, Prmt1 and Sestrin1 (Sesn1) were either overexpressed or inhibited in C2C12 myotubes to elucidate the underlying mechanism. Exercise preconditioning not only significantly improved muscle mass and motor ability in immobilized mice but also inhibited excessive activation of degradation pathways and enhanced protein synthesis. Importantly, Prmt1 mediated the protective effects of exercise preconditioning on muscle atrophy. Mechanistically, Prmt1 regulated the p38 mitogen-activated protein kinase (p38)/activating transcription factor 2 (ATF2) pathway, which modulates Sesn1 expression. Sesn1 acts as a downstream of Prmt1 and ATF2, contributing to the myoblast differentiation and skeletal muscle regeneration through AMP-Activated protein kinase α2 (AMPKα2)/transcriptional co-activator PPAR-γ co-activator-1 α (PGC-1α) signaling pathway. Taken together, our results highlighted the effectiveness of exercise preconditioning in preventing muscle atrophy via the Prmt1-Sesn1 pathway. • Concurrent exercise preconditioning prevents immobilization-induced muscle atrophy. • Prmt1 activity is crucial for exercise-induced improvement in muscle mass and strength. • Sestrin1, regulated by Prmt1-p38/ATF2 signaling, enhances muscle cell differentiation and regeneration. • Exercise activates PGC-1α signaling through Prmt1, promoting muscle regeneration and resisting atrophy.
DOI: 10.1016/j.smhs.2025.04.001
Language: English
Open Access status: diamond
OpenAlex ID: W4409201586
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Cites: 46
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