title: Expression of the Mas receptor is upregulated in skeletal muscle wasting.
abstract: Skeletal muscle atrophy during sepsis, immobilization, and chronic diseases is characterized by an increase in expression and activity of the muscle-specific ubiquitin 3 ligases atrogin-1 and MuRF-1. The classical renin-angiotensin system (RAS), by high level of circulating angiotensin II (AngII) is directly involved in skeletal muscle wasting associated with cardiac and renal failure. Ang (1-7), a peptide belonging to the non-classical RAS system, produces effects that are opposite to AngII. The actions of Ang (1-7) are mediated by its binding and signalling through the Mas receptor. Our purpose is to assess the effects of atrophic stimuli AngII, lipopolysaccharide (LPS), and immobilization on the expression of the Mas receptor in skeletal muscle. For that we used gastrocnemius and tibialis anterior muscles of C57BL10 mice treated with AngII, LPS or subjected to unilateral hindlimb immobilization by casting. In addition, we used C2C12 myotubes incubated with AngII or LPS. We evaluated Mas expression by quantitative real-time PCR, Western blot immunohistochemical analysis. Skeletal muscle atrophy was corroborated by the expression of atrogin-1 and MuRF-1 and the fibre diameter. Our results show that Mas receptor expression was increased by AngII or LPS in vitro and in vivo, and upregulated by immobilization. The increase of the Mas expression was concomitantly with the upregulation of atrogin-1 and MuRF-1 and the reduction of the fibre diameter. These results from studies in vitro and in vivo demonstrate for the first time that the Mas receptor is increased under atrophic stimulus and suggest that the non-classical RAS system could have an important role in muscle wasting.
authors.affiliation: Laboratorio de Biología y Fisiopatología Molecular, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas & Facultad de Medicina, Universidad Andres Bello, Avenida República 239, 8370146, Santiago, Chile.
authors.forename: María Gabriela
authors.initials: MG
authors.lastname: Morales
authors.forename: Johanna
authors.initials: J
authors.lastname: Abrigo
authors.forename: Carla
authors.initials: C
authors.lastname: Meneses
authors.forename: Franco
authors.initials: F
authors.lastname: Cisternas
authors.forename: Felipe
authors.initials: F
authors.lastname: Simon
authors.forename: Claudio
authors.initials: C
authors.lastname: Cabello-Verrugio
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D015151:Immunoblotting; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology*; D009133:Muscular Atrophy / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D011485:Protein Binding / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D008070:Lipopolysaccharides; D043562:Receptors, G-Protein-Coupled; D000804:Angiotensin II