Autophagy Signaling in Skeletal Muscle of Infarcted Rats

Author(s)

Jannig, Paulo R. ^{[1, 2]} ; Moreira, Jose B. N. ^{[2, 3]} ; Bechara, Luiz R. G. ^[2] ; Bozi, Luiz H. M. ^[2] ; Bacurau, Aline V. ^[2] ; Monteiro, Alex W. A. ^[2] ; Dourado, Paulo M. ^[4] ; Wisloff, Ulrik ^[3] ; Brum, Patricia C. ^{[2, 1]}

Affiliation

^[1] Univ Sao Paulo, Expt Physiopathol Med Sch, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Phys Educ & Sport, Sao Paulo - Brazil

^[3] Norwegian Univ Sci & Technol, KG Jensen Ctr Exercise Med, N-7034 Trondheim - Norway

^[4] Univ Sao Paulo, Sch Med, Inst Heart, Sao Paulo - Brazil

• Document type: Journal article
• Source: PLoS One; v. 9, n. 1 JAN 10 2014.
• Web of Science Citations: 31

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. Methods/Principal Findings: 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. (AU)

• FAPESP's process: 10/50048-1 - Cellular and functional bases of exercise in cardiovascular diseases
• Grantee: Carlos Eduardo Negrão
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 10/14567-4 - Role of the lysosomal/autophagic proteolytic system in skeletal muscle of animals with heart failure
• Grantee: Paulo Roberto Jannig
• Support Opportunities: Scholarships in Brazil - Master