title: Angiotensin-(1-7) attenuates disuse skeletal muscle atrophy in mice via its receptor, Mas.
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 atrophyin vivousing 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.
authors: Laboratory of Biology and Molecular Physiopathology, Department of Biological Sciences, Faculty of Biological Sciences & Faculty of Medicine, Universidad Andrés Bello, Santiago 8370146, Chile Millennium Institute on Immunology and Immunotherapy, Santiago 8370146, Chile.
authors: María Gabriela
authors: MG
authors: Morales
authors: Laboratory of Biology and Molecular Physiopathology, Department of Biological Sciences, Faculty of Biological Sciences & Faculty of Medicine, Universidad Andrés Bello, Santiago 8370146, Chile Millennium Institute on Immunology and Immunotherapy, Santiago 8370146, Chile.
authors: Johanna
authors: J
authors: Abrigo
authors: Center for Cell Regulation and Pathology (CRCP), Center for Regeneration and Aging (CARE), Laboratory of Cell Differentiation and Pathology, Department of Cell and Molecular Biology, Faculty of Biological Sciences, P. Universidad Católica de Chile, Santiago 8331150, Chile.
authors: María José
authors: MJ
authors: Acuña
authors: National Institute in Science and Technology in Nanobiopharmaceutics, Department of Physiology and Biophysics, Federal University of Minas Gerais (UFMG), Belo Horizonte 31270-901, Brazil.
authors: Robson A
authors: RA
authors: Santos
authors: Max-Delbrück-Center for Molecular Medicine, Berlin-Buch 13125, Germany National Institute in Science and Technology in Nanobiopharmaceutics, Belo Horizonte 31270-901, Brazil.
authors: Michael
authors: M
authors: Bader
authors: Center for Cell Regulation and Pathology (CRCP), Center for Regeneration and Aging (CARE), Laboratory of Cell Differentiation and Pathology, Department of Cell and Molecular Biology, Faculty of Biological Sciences, P. Universidad Católica de Chile, Santiago 8331150, Chile.
authors: Enrique
authors: E
authors: Brandan
authors: Laboratory of Integrative Physiopathology, Department of Biological Sciences, Faculty of Biological Sciences & Faculty of Medicine, Universidad Andrés Bello, Santiago 8370146, Chile Millennium Institute on Immunology and Immunotherapy, Santiago 8370146, Chile.
authors: Felipe
authors: F
authors: Simon
authors: Laboratory of Tissue Repair and Adult Stem Cells, Department of Cell and Molecular Biology, Faculty of Biological Sciences, P. Universidad Católica de Chile, Santiago 8331150, Chile.
authors: Hugo
authors: H
authors: Olguin
authors: Departamento de Ciencias Químicas y Biológicas, Facultad de Salud, Universidad Bernardo O Higgins, Santiago 8370993, Chile Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile.
authors: Daniel
authors: D
authors: Cabrera
authors: Laboratory of Biology and Molecular Physiopathology, Department of Biological Sciences, Faculty of Biological Sciences & Faculty of Medicine, Universidad Andrés Bello, Santiago 8370146, Chile Millennium Institute on Immunology and Immunotherapy, Santiago 8370146, Chile claudio.cabello@unab.cl.
authors: Claudio
authors: C
authors: Cabello-Verrugio
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009124:Muscle Proteins / Q000378:metabolism; D053580:Muscle Strength / Q000187:drug effects; D009133:Muscular Atrophy / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020966:Muscular Disorders, Atrophic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018995:Myosin Heavy Chains / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000070584:Tripartite Motif Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D009124:Muscle Proteins; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D000070584:Tripartite Motif Proteins; D007334:Insulin-Like Growth Factor I; D000803:Angiotensin I; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D018995:Myosin Heavy Chains; C118790:angiotensin I (1-7)
keywords: Angiotensin-(1-7); Atrophy; Disuse; Mas receptor; Skeletal muscle