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.

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.

• Authors: Paulo R Jannig, Jose B N Moreira, Luiz R G Bechara, Luiz H M Bozi, Aline V Bacurau, Alex W A Monteiro, Paulo M Dourado, Ulrik Wisløff, Patricia C Brum
• Journal: PloS one (PLoS One) Vol. 9 Issue 1 Pg. e85820 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24427319 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Map1lc3b protein, mouse
• Microtubule-Associated Proteins
• Cathepsin L

Topics

• Animals
• Autophagy (genetics)
• Biomarkers
• Cathepsin L (metabolism)
• Echocardiography
• Gene Expression Regulation
• Male
• Microtubule-Associated Proteins (genetics, metabolism)
• Mitochondria (metabolism)
• Muscular Atrophy (etiology, metabolism, pathology)
• Myocardial Infarction (complications, diagnosis, physiopathology)
• Oxidative Stress
• Physical Conditioning, Animal
• Rats
• Signal Transduction
• Transcriptome