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P38α-MAPK Signaling Inhibition Attenuates Soleus Atrophy during Early Stages of Muscle Unloading

Title: P38α-MAPK Signaling Inhibition Attenuates Soleus Atrophy during Early Stages of Muscle Unloading
Authors: Belova, Svetlana P.; Mochalova, Ekaterina P.; Kostrominova, Tatiana Y.; Shenkman, Boris S.; Nemirovskaya, Tatiana L.
Contributors: Anatomy and Cell Biology, School of Medicine
Source: PMC
Publisher Information: MDPI
Publication Year: 2020
Collection: Indiana University - Purdue University Indianapolis: IUPUI Scholar Works
Subject Terms: Muscle unloading; MuRF1; MAFbx; p38α-MAPK; Calpain-1; Ubiquitin
Description: 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.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
Relation: International Journal of Molecular Sciences; https://hdl.handle.net/1805/23483
Availability: https://hdl.handle.net/1805/23483
Rights: Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.B4186169
Database: BASE