Imoxin prevents dexamethasone-induced promotion of muscle-specific E3 ubiquitin ligases and stimulates anabolic signaling in C2C12 myotubes - 18/06/20
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Highlights |
• | Imoxin suppressed dexamethasone-induced skeletal muscle atrophy through suppression of MuRF1 and MAFbx. |
• | Imoxin prevented dexamethasone-induced nuclear FoxO3 accompanied with the upregulation of miR-23α and miR-182. |
• | Imoxin promoted Akt/mTOR anabolic signaling pathway which implies a role of PKR in the regulation of protein synthesis. |
Abstract |
Muscle atrophy is the loss of skeletal muscle mass during several pathological conditions such as long-term fasting, aging, cancer, diabetes, sepsis and immune disorders. Glucocorticoids are known to trigger skeletal muscle atrophy. Dexamethasone (DEX), a synthetic glucocorticoid, induces skeletal muscle atrophy by suppression of protein synthesis and promotion of protein degradation. The double-stranded RNA (dsRNA)-activated protein kinase R (PKR) plays a significant role in mediating lipopolysaccharide-induced inflammation. However, pathological roles of PKR in muscle atrophy are not fully understood. The current study aimed to investigate the effect of imoxin, a PKR inhibitor, on DEX-induced muscle atrophy in C2C12 myotubes. Myotubes were incubated with imoxin at different concentrations with or without 5 μM DEX for 24 h. In the current study, imoxin treatment significantly reduced protein levels of MuRF1 and MAFbx induced by DEX by 88 ± 2% and MAFbx by 99 ± 0%, respectively. Moreover, 5 μM imoxin treatment reduced protein ubiquitination by 42 ± 4% and protein content of nuclear FoxO3α (77 ± 4%) in presence of DEX. Furthermore, 5 μM imoxin treatment stimulated Akt phosphorylation (195 ± 5%), mTOR phosphorylation (171 ± 21 %) and p70S6K1 phosphorylation (314 ± 31 %) under DEX-treated condition even though DEX treatment did not suppressed Akt/mTOR/p70S6K1 axis. These findings suggest that imoxin may protect against DEX-induced skeletal muscle atrophy by alleviating muscle specific E3 ubiquitin ligases and imoxin alone may promote protein synthesis via Akt/mTOR/S6K1 axis in muscle cells.
Le texte complet de cet article est disponible en PDF.Keywords : Muscle atrophy, Imoxin, PKR, Dexamethasone, Ubiquitin-proteasome system, Atrogene
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Vol 128
Article 110238- août 2020 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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