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.
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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)
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Chemical References |
- Biomarkers
- Map1lc3b protein, mouse
- Microtubule-Associated Proteins
- Cathepsin L
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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
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