Skeletal muscle oxidative metabolism in an animal model of pulmonary emphysema: Formoterol and skeletal muscle dysfunction

Nikol Sullo, Fiorentina Roviezzo, Maria Matteis, Giuseppe Spaziano, Stefania Del Gaudio, Assunta Lombardi, Monica Lucattelli, Francesca Polverino, Giuseppe Lungarella, Giuseppe Cirino, Francesco Rossi, Bruno D'Agostino

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Skeletal muscle dysfunction is a significant contributor to exercise limitation in pulmonary emphysema. This study investigated skeletal muscle oxidative metabolism before and after aerosol exposure to a long-acting β-agonist (LABA), such as formoterol, in the pallid mouse (B6.Cg-Pldnpa/J), which has a deficiency in serum α1-antitrypsin (α1-PI) and develops spontaneous pulmonary emphysema. C57 BL/6J and its congener pallid mice of 8-12 and 16 months of age were treated with vehicle or formoterol aerosol challenge for 120 seconds. Morphological and morphometric studies and evaluations of mitochondrial adenosine diphosphate-stimulated respiration and of cytochrome oxidase activity on skeletal muscle were performed. Moreover, the mtDNA content in skeletal muscle and the mediators linked to muscle mitochondrial function and biogenesis, as well as TNF-α and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), were also evaluated. The lungs of pallid mice at 12 and 16 months of age showed patchy areas of airspace enlargements, with the destruction of alveolar septa. No significant differences were observed in basal values of mitochondrial skeletal muscle oxidative processes between C57 BL/6J and pallid mice. Exposure to LABA significantly improved mitochondrial skeletal muscle oxidative processes in emphysematous mice, where the mtDNA content was significantly higher with respect to 8-month-old pallid mice. This effect was compared with a significant increase of PGC-1α in skeletal muscles of 16-month-old pallid mice, withnosignificant changes in TNF-α concentrations. In conclusion, in emphysematous mice that showedan increased mtDNA content, exposure to inhaled LABA can improve mitochondrial skeletal muscle oxidative processes. PGC-1α may serve as a possible mediator of this effect.

Original languageEnglish (US)
Pages (from-to)198-203
Number of pages6
JournalAmerican journal of respiratory cell and molecular biology
Volume48
Issue number2
DOIs
StatePublished - Feb 2013
Externally publishedYes

Keywords

  • COX activity
  • Long-acting β-agonists
  • Mitochondrial adenosine diphosphate-stimulated respiration
  • Pulmonary emphysema
  • Skeletal muscle dysfunction

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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