title: Autophagy signaling in skeletal muscle of infarcted rats.
abstract: BACKGROUND
  Heart failure (HF)-induced skeletal muscle atrophy is often associated to exercise intolerance and poor prognosis. Better understanding of the molecular mechanisms underlying HF-induced muscle atrophy may contribute to the development of pharmacological strategies to prevent or treat such condition. It has been shown that autophagy-lysosome system is an important mechanism for maintenance of muscle mass. However, its role in HF-induced myopathy has not been addressed yet. Therefore, the aim of the present study was to evaluate autophagy signaling in myocardial infarction (MI)-induced muscle atrophy in rats.
  
  
  RESULTS
  Wistar rats underwent MI or Sham surgeries, and after 12 weeks were submitted to echocardiography, exercise tolerance and histology evaluations. Cathepsin L activity and expression of autophagy-related genes and proteins were assessed in soleus and plantaris muscles by fluorimetric assay, qRT-PCR and immunoblotting, respectively. MI rats displayed exercise intolerance, left ventricular dysfunction and dilation, thereby suggesting the presence of HF. The key findings of the present study were: a) upregulation of autophagy-related genes (GABARAPL1, ATG7, BNIP3, CTSL1 and LAMP2) was observed only in plantaris while muscle atrophy was observed in both soleus and plantaris muscles, and b) Cathepsin L activity, Bnip3 and Fis1 protein levels, and levels of lipid hydroperoxides were increased specifically in plantaris muscle of MI rats.
  
  
  CONCLUSIONS
  Altogether our results provide evidence for autophagy signaling regulation in HF-induced plantaris atrophy but not soleus atrophy. Therefore, autophagy-lysosome system is differentially regulated in atrophic muscles comprising different fiber-types and metabolic characteristics.
authors.affiliation: Experimental Physiopathology - Medical School, University of Sao Paulo, Sao Paulo, Brazil ; School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Paulo R
authors.initials: PR
authors.lastname: Jannig
authors.affiliation: School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, Brazil ; K. G. Jensen Center of Exercise in Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Jose B N
authors.initials: JB
authors.lastname: Moreira
authors.affiliation: School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Luiz R G
authors.initials: LR
authors.lastname: Bechara
authors.affiliation: School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Luiz H M
authors.initials: LH
authors.lastname: Bozi
authors.affiliation: School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Aline V
authors.initials: AV
authors.lastname: Bacurau
authors.affiliation: School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Alex W A
authors.initials: AW
authors.lastname: Monteiro
authors.affiliation: Heart Institute - Medical School, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Paulo M
authors.initials: PM
authors.lastname: Dourado
authors.affiliation: K. G. Jensen Center of Exercise in Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Ulrik
authors.initials: U
authors.lastname: Wisløff
authors.affiliation: Experimental Physiopathology - Medical School, University of Sao Paulo, Sao Paulo, Brazil ; School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Brum
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics; D015415:Biomarkers; D056668:Cathepsin L / Q000378:metabolism; D004452:Echocardiography; D005786:Gene Expression Regulation; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009133:Muscular Atrophy / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D009203:Myocardial Infarction / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal; D051381:Rats; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D015415:Biomarkers; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D056668:Cathepsin L