Evaluation of muscle-specific and metabolism regulating microRNAs in a chronic swimming rat model

Making benefit from the epigenetic effects of environmental factors such as physical activity may result in a considerable improvement in the prevention of chronic civilization diseases. In our chronic swimming rat model, the expression levels of such microRNAs were characterized, that are involved in skeletal muscle differentiation, hypertrophy and fine-tuning of metabolism, which processes are influenced by chronic endurance training, contributing to the metabolic adaptation of skeletal muscle during physical activity. After chronic swimming, the level of miR-128a increased significantly in EDL muscles, which may influence metabolic adaptation and stress response as well. In SOL, the expression level of miR-15b and miR-451 decreased significantly after chronic swimming, which changes are opposite to their previously described increment in insulin resistant skeletal muscle. MiR-451 also targets PGC-1α mRNA, whiches expression level significantly increased in SOL muscles, resulting in enhanced biogenesis and oxidative capacity of mitochondria. In summary, the microRNA expression changes that were observed during our experiments suggest that chronic swim training contributes to a beneficial metabolic profile of skeletal muscle.

2-D08 treatment regulates C2C12 myoblast proliferation and differentiation via the Erk1/2 and proteasome signaling pathways

SUMOylation is one of the post-translational modifications that involves the covalent attachment of the small ubiquitin-like modifier (SUMO) to the substrate. SUMOylation regulates multiple biological processes, including myoblast proliferation, differentiation, and apoptosis. 2-D08 is a synthetically available flavone, which acts as a potent cell-permeable SUMOylation inhibitor. Its mechanism of action involves preventing the transfer of SUMO from the E2 thioester to the substrate without influencing SUMO-activating enzyme E1 (SAE-1/2) or E2 Ubc9-SUMO thioester formation. However, both the effects and mechanisms of 2-D08 on C2C12 myoblast cells remain unclear. In the present study, we found that treatment with 2-D08 inhibits C2C12 cell proliferation and differentiation. We confirmed that 2-D08 significantly hampers the viability of C2C12 cells. Additionally, it inhibited myogenic differentiation, decreasing myosin heavy chain (MHC), MyoD, and myogenin expression. Furthermore, we confirmed that 2-D08-mediated anti-myogenic effects impair myoblast differentiation and myotube formation, reducing the number of MHC-positive C2C12 cells. In addition, we found that 2-D08 induces the activation of ErK1/2 and the degradation of MyoD and myogenin in C2C12 cells. Taken together, these results indicated that 2-D08 treatment results in the deregulated proliferation and differentiation of myoblasts. However, further research is needed to investigate the long-term effects of 2-D08 on skeletal muscles.

Mfge8 attenuates human gastric antrum smooth muscle contractions

Coordinated gastric smooth muscle contraction is critical for proper digestion and is adversely affected by a number of gastric motility disorders. In this study we report that the secreted protein Mfge8 (milk fat globule-EGF factor 8) inhibits the contractile responses of human gastric antrum muscles to cholinergic stimuli by reducing the inhibitory phosphorylation of the MYPT1 (myosin phosphatase-targeting subunit (1) subunit of MLCP (myosin light chain phosphatase), resulting in reduced LC20 (smooth muscle myosin regulatory light chain (2) phosphorylation. Mfge8 reduced the agonist-induced increase in the F-actin/G-actin ratios of β-actin and γ-actin1. We show that endogenous Mfge8 is bound to its receptor, α8β1 integrin, in human gastric antrum muscles, suggesting that human gastric antrum muscle mechanical responses are regulated by Mfge8. The regulation of gastric antrum smooth muscles by Mfge8 and α8 integrin functions as a brake on gastric antrum mechanical activities. Further studies of the role of Mfge8 and α8 integrin in regulating gastric antrum function will likely reveal additional novel aspects of gastric smooth muscle motility mechanisms.