Belova, Svetlana P.Mochalova, Ekaterina P.Kostrominova, Tatiana Y.Shenkman, Boris S.Nemirovskaya, Tatiana L.2020-07-312020-07-312020-04-15Belova, S. P., Mochalova, E. P., Kostrominova, T. Y., Shenkman, B. S., & Nemirovskaya, T. L. (2020). P38α-MAPK Signaling Inhibition Attenuates Soleus Atrophy during Early Stages of Muscle Unloading. International journal of molecular sciences, 21(8), 2756. https://doi.org/10.3390/ijms21082756https://hdl.handle.net/1805/23483To test the hypothesis that p38α-MAPK plays a critical role in the regulation of E3 ligase expression and skeletal muscle atrophy during unloading, we used VX-745, a selective p38α inhibitor. Three groups of rats were used: non-treated control (C), 3 days of unloading/hindlimb suspension (HS), and 3 days HS with VX-745 inhibitor (HSVX; 10 mg/kg/day). Total weight of soleus muscle in HS group was reduced compared to C (72.3 ± 2.5 vs 83.0 ± 3 mg, respectively), whereas muscle weight in the HSVX group was maintained (84.2 ± 5 mg). The expression of muscle RING-finger protein-1 (MuRF1) mRNA was significantly increased in the HS group (165%), but not in the HSVX group (127%), when compared with the C group. The expression of muscle-specific E3 ubiquitin ligases muscle atrophy F-box (MAFbx) mRNA was increased in both HS and HSVX groups (294% and 271%, respectively) when compared with C group. The expression of ubiquitin mRNA was significantly higher in the HS (423%) than in the C and HSVX (200%) groups. VX-745 treatment blocked unloading-induced upregulation of calpain-1 mRNA expression (HS: 120%; HSVX: 107%). These results indicate that p38α-MAPK signaling regulates MuRF1 but not MAFbx E3 ligase expression and inhibits skeletal muscle atrophy during early stages of unloading.en-USAttribution 4.0 InternationalMuscle unloadingMuRF1MAFbxp38α-MAPKCalpain-1UbiquitinArticle