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

Maria Gabriela Morales, Johanna Abrigo, Maria Jose Acuna, Robson A. Santos, Michael Bader, Enrique Brandan, Felipe Simon, Hugo Olguin, Daniel Cabrera, Claudio Cabello-Verrugio

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

68 Citas (Scopus)

Resumen

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 myofiber 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.

Idioma originalInglés
Páginas (desde-hasta)441-449
Número de páginas9
PublicaciónDMM Disease Models and Mechanisms
Volumen9
N.º4
DOI
EstadoPublicada - 1 abr. 2016

Áreas temáticas de ASJC Scopus

  • Neurociencia (miscelánea)
  • Medicina (miscelánea)
  • Inmunología y microbiología (miscelánea)
  • Bioquímica, Genética y Biología Molecular General

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