Angiotensin-(1-7) decreases skeletal muscle atrophy induced by angiotensin II through a Mas receptor-dependent mechanism.
Clin Sci (Lond)
; 128(5): 307-19, 2015 Mar.
Article
em En
| MEDLINE
| ID: mdl-25222828
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Angiotensina I
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Angiotensina II
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Atrofia Muscular
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Proteínas Proto-Oncogênicas
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Músculo Esquelético
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Receptores Acoplados a Proteínas G
Limite:
Animals
Idioma:
En
Revista:
Clin Sci (Lond)
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Chile
País de publicação:
Reino Unido