1. Calpastatin overexpression in the skeletal muscle of mice prevents clenbuterol-induced muscle hypertrophy and phenotypic shift
- Author
-
Anne Bonnieu, Aymeric Douillard, Olivier Galbes, Guillaume Py, Barbara Vernus, Robin Candau, Gwenaelle Begue, John Levin, Bernadette Rossano, Dynamique Musculaire et Métabolisme (DMEM), and Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM)
- Subjects
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 - Abstract
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.
- Published
- 2012