title: Skeletal muscle oxidative metabolism in an animal model of pulmonary emphysema: formoterol and skeletal muscle dysfunction.
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 α(1)-antitrypsin (α(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-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, with no significant changes in TNF-α concentrations. In conclusion, in emphysematous mice that showed an 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.
authors.affiliation: Section of Pharmacology, Department of Experimental Medicine, Faculty of Medicine and Surgery, Second University of Naples, Via Costantinopoli 16, 80136 Naples, Italy.
authors.forename: Nikol
authors.initials: N
authors.lastname: Sullo
authors.forename: Fiorentina
authors.initials: F
authors.lastname: Roviezzo
authors.forename: Maria
authors.initials: M
authors.lastname: Matteis
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Spaziano
authors.forename: Stefania
authors.initials: S
authors.lastname: Del Gaudio
authors.forename: Assunta
authors.initials: A
authors.lastname: Lombardi
authors.forename: Monica
authors.initials: M
authors.lastname: Lucattelli
authors.forename: Francesca
authors.initials: F
authors.lastname: Polverino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lungarella
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cirino
authors.forename: Francesco
authors.initials: F
authors.lastname: Rossi
authors.forename: Bruno
authors.initials: B
authors.lastname: D'Agostino
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology*; D004272:DNA, Mitochondrial / Q000378:metabolism; D004195:Disease Models, Animal; D004646:Emphysema / Q000378:metabolism* / Q000503:physiopathology; D004983:Ethanolamines / Q000494:pharmacology*; D000068759:Formoterol Fumarate; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology; D010084:Oxidation-Reduction; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D004272:DNA, Mitochondrial; D004983:Ethanolamines; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000068759:Formoterol Fumarate