| First Author | Sullo N | Year | 2013 |
| Journal | Am J Respir Cell Mol Biol | Volume | 48 |
| Issue | 2 | Pages | 198-203 |
| PubMed ID | 23144332 | Mgi Jnum | J:205093 |
| Mgi Id | MGI:5544001 | Doi | 10.1165/rcmb.2012-0167OC |
| Citation | Sullo N, et al. (2013) Skeletal muscle oxidative metabolism in an animal model of pulmonary emphysema: formoterol and skeletal muscle dysfunction. Am J Respir Cell Mol Biol 48(2):198-203 |
| abstractText | 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 beta-agonist (LABA), such as formoterol, in the pallid mouse (B6.Cg-Pldnpa/J), which has a deficiency in serum alpha(1)-antitrypsin (alpha(1)-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-alpha and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha), 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-1alpha in skeletal muscles of 16-month-old pallid mice, with no significant changes in TNF-alpha concentrations. In conclusion, in emphysematous mice that showed an increased mtDNA content, exposure to inhaled LABA can improve mitochondrial skeletal muscle oxidative processes. PGC-1alpha may serve as a possible mediator of this effect. |
