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Cellular mechanisms underlying temporal changes in skeletal muscle protein synthesis and breakdown during chronic beta-adrenoceptor stimulation in mice

Authors :
Koopman, René
Gehrig, Stefan M.
Léger, Bertrand
Trieu, Jennifer
Walrand, Stéphane
Murphy, Kate T.
Lynch, Gordon S.
University of Melbourne
Unité de Nutrition Humaine (UNH)
Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA)
National Health & Medical Research Council (NHMRC, Australia) [509313]
Association Francaise contre les Myopathies (France)
Faculty of Medicine, Dentistry and Health Sciences of The University of Melbourne
Swiss National Funds
National Heart Foundation (Australia)
Source :
The Journal of Physiology, The Journal of Physiology, Wiley, 2010, 588 (23), pp.4811-4823. ⟨10.1113/jphysiol.2010.196725⟩
Publication Year :
2010
Publisher :
HAL CCSD, 2010.

Abstract

International audience; Chronic stimulation of beta-adrenoceptors with beta-adrenoceptor agonists (beta-agonists) can induce substantial skeletal muscle hypertrophy, but the mechanisms mediating this muscle growth have yet to be elucidated. We investigated whether chronic beta-adrenoceptor stimulation in mice with the beta-agonist formoterol alters the muscle anabolic response following beta-adrenoceptor stimulation. Twelve-week-old C57BL/6 mice were treated for up to 28 days with a once-daily injection of either saline (control, n = 9) or formoterol (100 mu g kg-1; n = 9). Rates of muscle protein synthesis were assessed at either 1, 7 or 28 days of treatment, 6 h after injection. Protein synthesis rates were higher in formoterol-treated mice at day 7 (similar to 1.5-fold, P < 0.05), but not at day 1 or 28. The increased muscle protein synthesis was associated with increased phosphorylation of S6K1 (r = 0.49, P < 0.01). Formoterol treatment acutely reduced maximal calpain activity by similar to 25% (P < 0.05) but did not affect atrogin-1 protein levels and proteasome-mediated proteolytic activity, despite significantly enhanced phosphorylation of Akt (P < 0.05). Formoterol increased CREB phosphorylation by similar to 30% (P < 0.05) and PPAR gamma coactivator-1 alpha (PGC-1 alpha) by 11-fold (P < 0.05) on day 1 only. These observations identify that formoterol treatment induces muscle anabolism, by reducing calpain activity and by enhancing protein synthesis via increased PI-3 kinase/Akt signalling.

Details

Language :
English
ISSN :
00223751 and 14697793
Database :
OpenAIRE
Journal :
The Journal of Physiology, The Journal of Physiology, Wiley, 2010, 588 (23), pp.4811-4823. ⟨10.1113/jphysiol.2010.196725⟩
Accession number :
edsair.dedup.wf.001..93ac50fb1dd92135dd61bf56ec2a080c