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Angiotensin-(1-7) attenuates disuse skeletal muscle atrophy in mice via its receptor, Mas

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Item Type:Article
Title:Angiotensin-(1-7) attenuates disuse skeletal muscle atrophy in mice via its receptor, Mas
Creators Name:Morales, M.G. and Abrigo, J. and Acuna, M.J. and Santos, R.A. and Bader, M. and Brandan, E. and Simonetta, F. and Olguin, H. and Cabrera, D. and Cabello-Verrugio, C.
Abstract:Immobilization is a form of disuse characterized by a loss of strength and muscle mass. Among the main features are decreased IGF-1/Akt signalling and increased ubiquitin-proteasome pathway signalling, which induce greater myosin heavy chain degradation. Activation of the classical renin-angiotensin system (RAS) causes deleterious effects in skeletal muscle, including muscle wasting. In contrast, angiotensin-(1-7) [Ang-(1-7)], a peptide of the non-classical RAS, produces beneficial effects in skeletal muscle. However, the role of Ang-(1-7) in skeletal muscle disuse atrophy and independent of classical RAS activation has not been evaluated. Therefore, we assessed the functions of Ang-(1-7) and the Mas receptor in disuse muscle atrophy in vivo using unilateral cast immobilization of the hind limb in male, 12-week-old wild-type (WT) and Mas knockout (Mas KO) mice for 1 and 14 days. Additionally, we evaluated the participation of IGF-1/IGFR-1/Akt signalling and ubiquitin-proteasome pathway expression on the effects of Ang-(1-7) immobilization-induced muscle atrophy. Our results found that Ang-(1-7) prevented decreased muscle strength and reduced myofibre diameter, myosin heavy chain levels, and the induction of atrogin-1 and MuRF-1 expressions, all of which normally occur during immobilization. Analyses indicated that Ang-(1-7) increases IGF-1/IGFR-1/Akt pathway signalling through IGFR-1 and Akt phosphorylation, and the concomitant activation of two downstream targets of Akt, p70S6K and FoxO3. These anti-atrophic effects of Ang-(1-7) were not observed in Mas KO mice, indicating crucial participation of the Mas receptor. This report is the first to propose anti-atrophic effects of Ang-(1-7) via the Mas receptor and the participation of the IGF-1/IGFR-1/Akt/p70S6K/FoxO3 mechanism in disuse skeletal muscle atrophy.
Keywords:Disuse, Angiotensin-(1-7), Mas Receptor, Skeletal Muscle, Atrophy, Animals, Mice
Source:Disease Models & Mechanisms
ISSN:1754-8403
Publisher:Company of Biologists
Volume:9
Number:4
Page Range:441-449
Date:1 April 2016
Official Publication:https://doi.org/10.1242/dmm.023390
PubMed:View item in PubMed

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