Effects of exercise on mitochondrial DNA content in skeletal muscle of patients with COPD

• Published in: Thorax Vol. 66; no. 2; pp. 121 - 127
• Main Authors: Puente-Maestu, Luis, Lázaro, Alberto, Tejedor, Alberto, Camaño, Sonia, Fuentes, Marta, Cuervo, Miguel, Navarro, Beatriz Oláiz, Agustí, Alvar
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Thoracic Society 01.02.2011; BMJ Publishing Group; BMJ Publishing Group LTD
• Subjects: Aged; Biological and medical sciences; Biopsy; Body mass index; Cardiology. Vascular system; Case-Control Studies; Chronic obstructive pulmonary disease; Chronic obstructive pulmonary disease, asthma; coactivator-1α; COPD mechanisms; DNA damage; DNA, Mitochondrial - metabolism; Exercise; Exercise - physiology; Humans; Investigations; Lactic Acid - biosynthesis; Medical sciences; Middle Aged; mitochondria biogenesis; Mitochondria, Muscle - metabolism; Mitochondrial DNA; Muscle, Skeletal - metabolism; Musculoskeletal system; Oxidation; oxidative stress; Oxidative Stress - genetics; Oxygen Consumption - physiology; peroxisome proliferator-activated receptor-γ; Pneumology; Polymerase Chain Reaction - methods; Prospective Studies; Pulmonary Disease, Chronic Obstructive - genetics; Pulmonary Disease, Chronic Obstructive - metabolism; pulmonary rehabilitation; quadriceps muscle injury; Reactive Oxygen Species - metabolism; Spirometry; Spirometry - methods; superoxide dismutase; Ventilation; United States > US; Germany; California; Physical exercise; Human; Lung disease; Respiratory disease; Patient; Mitochondrial DNA; Striated muscle; Chronic; Bronchus disease; Anesthesia; Exercise tolerance test; Chronic obstructive pulmonary disease; Circulatory system; Obstructive pulmonary disease; Cardiology
• ISSN: 0040-6376; 1468-3296; 1468-3296
• DOI: 10.1136/thx.2010.153031

BackgroundExhausting exercise reduces the mitochondrial DNA (mtDNA) content in the skeletal muscle of healthy subjects due to oxidative damage. Since patients with chronic obstructive pulmonary disease (COPD) suffer enhanced oxidative stress during exercise, it was hypothesised that the mtDNA content will be further reduced.ObjectiveTo investigate the effects of exercise above and below the lactate threshold (LT) on the mtDNA content of skeletal muscle of patients with COPD.MethodsEleven patients with COPD (67±8 years; forced expiratory volume in 1 s (FEV1) 45±8%ref) and 10 healthy controls (66±4 years; FEV1 90±7% ref) cycled 45 min above LT (65% peak oxygen uptake (V′o2peak) and another 7 patients (65±6 years; FEV1 50±4%ref) and 7 controls (56±9 years; FEV1 92±6%ref) cycled 45 min below their LT (50% V′o2peak). Biopsies from the vastus lateralis muscle were obtained before exercise, immediately after and 1 h, 1 day and 1 week later to determine by PCR the mtDNA/nuclear DNA (nDNA) ratio (a marker of mtDNA content) and the expression of the peroxisome proliferator-activated receptor-γcoactivator-1α (PGC-1α) mRNA and the amount of reactive oxygen species produced during exercise was estimated from total V′o2.ResultsSkeletal muscle mtDNA/nDNA fell significantly after exercise above the LT both in controls and in patients with COPD, but the changes were greater in those with COPD. These changes correlated with production of reactive oxygen species, increases in manganese superoxide dismutase and PGC-1α mRNA and returned to baseline values 1 week later. This pattern of response was also observed, albeit minimised, in patients exercising below the LT.ConclusionsIn patients with COPD, exercise enhances the decrease in mtDNA content of skeletal muscle and the expression of PGC-1α mRNA seen in healthy subjects, probably due to oxidative stress.