Skeletal muscle atrophy is a pathological condition characterized by the loss of strength and muscle mass, an increase in myosin heavy chain (MHC) degradation and increase in the expression of two muscle-specific ubiquitin ligases: atrogin-1 and MuRF-1. Angiotensin II (AngII) induces muscle atrophy. Angiotensin-(1–7) [Ang-(1–7)], through its receptor Mas, produces the opposite effects than AngII. We assessed the effects of Ang-(1–7) on the skeletal muscle atrophy induced by AngII. Our results show that Ang-(1–7), through Mas, prevents the effects induced by AngII in muscle gastrocnemius: the decrease in the fibre diameter, muscle strength and MHC levels and the increase in atrogin-1 and MuRF-1. Ang-(1–7) also induces AKT phosphorylation. In addition, our analysis in vitro using C2C12 myotubes shows that Ang-(1–7), through a mechanism dependent on Mas, prevents the decrease in the levels of MHC and the increase in the expression of the atrogin-1 and MuRF-1, both induced by AngII. Ang-(1–7) induces AKT phosphorylation in myotubes; additionally, we demonstrated that the inhibition of AKT with MK-2206 decreases the anti-atrophic effects of Ang-(1–7). Thus, we demonstrate for the first time that Ang-(1–7) counteracts the skeletal muscle atrophy induced by AngII through a mechanism dependent on the Mas receptor, which involves AKT activity. Our study indicates that Ang-(1–7) is novel molecule with a potential therapeutical use to improve muscle wasting associated, at least, with pathologies that present high levels of AngII.
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Research Article|
November 05 2014
Angiotensin-(1–7) decreases skeletal muscle atrophy induced by angiotensin II through a Mas receptor-dependent mechanism
Franco Cisternas;
Franco Cisternas
1
*Laboratorio de Biología y Fisiopatología Molecular, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas & Facultad de Medicina, Universidad Andres Bello, Santiago, Chile
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María Gabriela Morales;
María Gabriela Morales
1
*Laboratorio de Biología y Fisiopatología Molecular, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas & Facultad de Medicina, Universidad Andres Bello, Santiago, Chile
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Carla Meneses;
Carla Meneses
*Laboratorio de Biología y Fisiopatología Molecular, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas & Facultad de Medicina, Universidad Andres Bello, Santiago, Chile
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Felipe Simon;
Felipe Simon
†Laboratorio de Fisiopatología Integrativa, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas & Facultad de Medicina, Universidad Andres Bello, Santiago, Chile
‡Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
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Enrique Brandan;
Enrique Brandan
§Centro de Regulación Celular y Patología (CRCP), Centro de Regeneración y Envejecimiento (CARE), Laboratorio de Diferenciación Celular y Patología, Departamento de Biología Celular y Molecular, MIFAB, Pontificia Universidad Católica de Chile, Santiago, Chile
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Johanna Abrigo;
Johanna Abrigo
*Laboratorio de Biología y Fisiopatología Molecular, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas & Facultad de Medicina, Universidad Andres Bello, Santiago, Chile
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Yaneisi Vazquez;
Yaneisi Vazquez
*Laboratorio de Biología y Fisiopatología Molecular, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas & Facultad de Medicina, Universidad Andres Bello, Santiago, Chile
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Claudio Cabello-Verrugio
*Laboratorio de Biología y Fisiopatología Molecular, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas & Facultad de Medicina, Universidad Andres Bello, Santiago, Chile
Correspondence: Dr Claudio Cabello-Verrugio (email claudio.cabello@unab.cl).
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Publisher: Portland Press Ltd
Received:
April 07 2014
Revision Received:
August 06 2014
Accepted:
September 15 2014
Accepted Manuscript online:
September 15 2014
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2015 Biochemical Society
2015
Clin Sci (Lond) (2015) 128 (5): 307–319.
Article history
Received:
April 07 2014
Revision Received:
August 06 2014
Accepted:
September 15 2014
Accepted Manuscript online:
September 15 2014
Citation
Franco Cisternas, María Gabriela Morales, Carla Meneses, Felipe Simon, Enrique Brandan, Johanna Abrigo, Yaneisi Vazquez, Claudio Cabello-Verrugio; Angiotensin-(1–7) decreases skeletal muscle atrophy induced by angiotensin II through a Mas receptor-dependent mechanism. Clin Sci (Lond) 1 March 2015; 128 (5): 307–319. doi: https://doi.org/10.1042/CS20140215
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