The role of the PI3K/AKT/mTOR protein synthesis pathway in the skeletal muscle atrophy induced by COPD

Objective: To confirm the role of PI3K/AKT/mTOR protein synthesis pathway in skeletal muscle atrophy induced by chronic obstructive pulmonary disease (COPD), and to explore the possible targets in the signaling pathway inhibiting muscle atrophy. Methods: Rats exposed to chronic cigarette smoke (CS) were selected for our study, divided into two exposure groups sham-exposed and 12 weeks CS. Total RNA and protein were extracted from extensor digitorum longus muscle (EDLM) for Real-time PCR and Western blot analysis to assess the MHC expression. The proteins expression associated with PI3K/AKT/mTOR signaling pathway (PI3K, Akt, mTOR, GSK-3 beta, p70S6K1, and 4EBP1) were assessed by Western blot analysis. 2% FBS induces L6 cells to differentiate. IGF-1 (PI3K agonist) and 10% CSE exposed L6 myoblasts for 24 hours, then detect the expression of MHC, and the proteins associated with PI3K/AKT/mTOR signaling pathway. Results: Chronic CS exposure decreased the MHC expression. The phosphorylation levels of Akt, mTOR, GSK-3 beta, p70S6K1 and 4EBP1 were increased significantly after Chronic CS exposure, and no significant changes were observed in the protein levels of PI3K. CSE treatment also decreased MHC expression. PI3K agonist insulin-like growth factor (IGF-1) treatment increased the MHC expression in comparison with simple CSE treatment. Not only the phosphorylation levels of Akt, mTOR, GSK-3 beta, p70S6K1, and 4EBP1 decreased significantly after CSE treatment, but also PI3K. Moreover, IGF-1 increased the phosphorylation levels of the protein synthesis pathway in comparison with simple CSE treatment. Conclusion: Chronic CS exposure induces muscle atrophy and activates PI3K/AKT/mTOR signaling pathway. Using IGF-1 activates PI3K/AKT/mTOR signaling pathway inhibits L6 myoblasts atrophy induced by CSE.