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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., Abrigo, J., Acuna, M.J., Santos, R.A., Bader, M., Brandan, E., Simonetta, F., Olguin, H., 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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