P38α-MAPK Signaling Inhibition Attenuates Soleus Atrophy during Early Stages of Muscle Unloading
Open Access
- 15 April 2020
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 21 (8), 2756
- https://doi.org/10.3390/ijms21082756
Abstract
To 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.Funding Information
- Russian Science Foundation (18-15-00062)
This publication has 51 references indexed in Scilit:
- Longitudinal characterization of functional, morphologic, and biochemical adaptations in mouse skeletal muscle with hindlimb suspensionMuscle & Nerve, 2013
- p38β MAPK upregulates atrogin1/MAFbx by specific phosphorylation of C/EBPβSkeletal Muscle, 2012
- Various Jobs of Proteolytic Enzymes in Skeletal Muscle during Unloading: Facts and SpeculationsJournal of Biomedicine and Biotechnology, 2012
- MAFbx/Atrogin-1 expression is a poor index of muscle proteolysisCurrent Opinion in Clinical Nutrition and Metabolic Care, 2010
- Regulation of the Intracellular Localization of Foxo3a by Stress-Activated Protein Kinase Signaling Pathways in Skeletal Muscle CellsMolecular and Cellular Biology, 2010
- P38 MAP kinase inhibitors as potential therapeutics for the treatment of joint degeneration and pain associated with osteoarthritisJournal of Inflammation, 2008
- The E3 Ligase MuRF1 Degrades Myosin Heavy Chain Protein in Dexamethasone-Treated Skeletal MuscleCell Metabolism, 2007
- Signalling pathways that mediate skeletal muscle hypertrophy and atrophyNature, 2003
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001
- Mechanism of elongation factor 2 (EF‐2) inactivation upon phosphorylation Phosphorylated EF‐2 is unable to catalyze translocationFEBS Letters, 1989