title: Angiotensin-(1-7) Prevents Skeletal Muscle Atrophy Induced by Transforming Growth Factor Type Beta (TGF-β) via Mas Receptor Activation.
abstract: BACKGROUND
  Transforming growth factor type beta 1 (TGF-β1) produces skeletal muscle atrophy. Angiotensin-(1-7) (Ang-(1-7)), through the Mas receptor, prevents the skeletal muscle atrophy induced by sepsis, immobilization, or angiotensin II (Ang-II). However, the effect of Ang-(1-7) on muscle wasting induced by TGF-β1 is unknown.
  
  
  OBJECTIVE
  To evaluate whether Ang-(1-7)/Mas receptor axis could prevent the skeletal muscle atrophy induced by TGF-β1.
  
  
  METHODS
  This study assessed the atrophic effect of TGF-β1 in C2C12 myotubes and mice in absence or presence of Ang-(1-7), and the receptor participation using A779, an antagonist of the Mas receptor. The levels of myosin heavy chain (MHC), polyubiquitination, and MuRF-1 were detected by western blot. Myotube diameter was also evaluated. In vivo analysis included the muscle strength, fibre diameter, MHC and MuRF-1 levels by western blot, and ROS levels by DCF probe detection.
  
  
  RESULTS
  The results showed that Ang-(1-7) prevented the increase in MuRF-1 and polyubiquitined protein levels, the decrease of MHC levels, the myotubes/fibre diameter diminution, and the increased production of reactive oxygen species (ROS) induced by TGF-β1. Utilizing A779 inhibited the anti-atrophic effect of Ang-(1-7).
  
  
  CONCLUSIONS
  The preventive effect of Ang-(1-7) on skeletal muscle atrophy induced by TGF-β1 is produced through inhibition of ROS production and proteasomal degradation of MHC.
authors.affiliation: Departmento de Ciencias Biologicas, Facultad de Ciencias Biologicas and Facultad de Medicina, Universidad Andres Bello, Santiago, Chile.
authors.forename: Johanna
authors.initials: J
authors.lastname: Ábrigo
authors.forename: Felipe
authors.initials: F
authors.lastname: Simon
authors.forename: Daniel
authors.initials: D
authors.lastname: Cabrera
authors.forename: Claudio
authors.initials: C
authors.lastname: Cabello-Verrugio
mesh_terms: D000803:Angiotensin I / Q000627:therapeutic use*; D000818:Animals; D002460:Cell Line; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal; D009133:Muscular Atrophy / Q000188:drug therapy* / Q000473:pathology; D018995:Myosin Heavy Chains / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D010446:Peptide Fragments / Q000627:therapeutic use*; D025821:Polyubiquitin / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D000070584:Tripartite Motif Proteins / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination / Q000187:drug effects
chemical_list: D009124:Muscle Proteins; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D017382:Reactive Oxygen Species; D043562:Receptors, G-Protein-Coupled; D016212:Transforming Growth Factor beta; D000070584:Tripartite Motif Proteins; D025801:Ubiquitin; D025821:Polyubiquitin; D000803:Angiotensin I; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex; D018995:Myosin Heavy Chains; D009218:Myosins; C118790:angiotensin I (1-7)