Calpastatin overexpression in the skeletal muscle of mice prevents clenbuterol-induced muscle hypertrophy and phenotypic shift
Autor: | Anne Bonnieu, Aymeric Douillard, Olivier Galbes, Guillaume Py, Barbara Vernus, Robin Candau, Gwenaelle Begue, John Levin, Bernadette Rossano |
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Přispěvatelé: | Dynamique Musculaire et Métabolisme (DMEM), Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM) |
Rok vydání: | 2012 |
Předmět: |
Male
medicine.medical_specialty muscle Physiology [SDV]Life Sciences [q-bio] phenotypic shift alpastatine Muscle hypertrophy clenbuterol Mice 03 medical and health sciences alpaïne 0302 clinical medicine Physiology (medical) Internal medicine medicine Animals changements phénotypiques [INFO]Computer Science [cs] Muscle Skeletal Protein kinase B mouse PI3K/AKT/mTOR pathway 030304 developmental biology Calpastatin Pharmacology 0303 health sciences biology Chemistry Calcium-Binding Proteins calpastatin Skeletal muscle AMPK Calpain Phenotype décalage phénotypique medicine.anatomical_structure Endocrinology Gene Expression Regulation Ribosomal protein s6 Mice Inbred CBA biology.protein Cattle hypertrophy calpain hypertrophie du muscle squelettique 030217 neurology & neurosurgery |
Zdroj: | Clinical and Experimental Pharmacology and Physiology Clinical and Experimental Pharmacology and Physiology, Wiley, 2012, 39 (4), pp.364-372. ⟨10.1111/j.1440-1681.2012.05677.x⟩ |
ISSN: | 0305-1870 1440-1681 |
Popis: | Contact: aymerichpz@yahoo.fr; International audience; Accumulating evidence suggests that the calpain/calpastatin system is involved in skeletal muscle remodelling induced by beta 2-adrenoceptor agonist treatment. In addition to other pathways, the Akt/mammalian target of rapamycin (mTOR) pathway, controlling protein synthesis, and the calcium/calmodulin-dependent protein kinase 2 (CamK2) and AMP-activated protein kinase (AMPK) pathways, recently identified as calpain substrates, could be relevant in beta 2-adrenoceptor agonist-induced skeletal muscle remodelling. In the present study we investigated muscle hypertrophy and phenotypic shifts, as well as the molecular response of components of the Akt/mTOR pathway (i.e. Akt, eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), ribosomal protein S6 (rpS6), CamK2 and AMPK), in response to calpastatin overexpression in the skeletal muscle of mice treated with 1mg/kg per day clenbuterol for 21days. Using gene electrotransfer of a calpastatin expression vector into the tibialis anterior of adult mice, we found that calpastatin overexpression attenuates muscle hypertrophy and phenotypic shifts induced by clenbuterol treatment. At the molecular level, calpastatin overexpression markedly decreased calpain activity, but was ineffective in altering the phosphorylation of Akt, 4E-BP1 and rpS6. In contrast, calpastatin overexpression increased the protein expression of both total AMPK and total CamK2. In conclusion, the results support the contention that the calpain/calpastatin system plays a crucial role in skeletal muscle hypertrophy and phenotypic shifts under chronic clenbuterol treatment, with AMPK and CamK2 probably playing a minor role. Moreover, the calpastatin-induced inhibition of hypertrophy under clenbuterol treatment was not related to a decreased mTOR-dependent initiation of protein translation. |
Databáze: | OpenAIRE |
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