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

Background Exhausting 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. Objective To investigate the effects of exercise above and below the lactate threshold (LT) on the mtDNA content of skeletal muscle of patients with COPD. Methods Eleven patients with COPD (67 +/- 8 years; forced expiratory volume in 1 s (FEV(1)) 45 +/- 8% ref) and 10 healthy controls (66 +/- 4 years; FEV(1) 90 +/- 7% ref) cycled 45 min above LT (65% peak oxygen uptake (V' O(2)peak) and another 7 patients (65 +/- 6 years; FEV(1) 50 +/- 4% ref) and 7 controls (56 +/- 9 years; FEV(1) 92 +/- 6% ref) cycled 45 min below their LT (50% V' O(2)peak). 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-gamma coactivator-1 alpha (PGC-1 alpha) mRNA and the amount of reactive oxygen species produced during exercise was estimated from total V'O(2). Results Skeletal 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-1 alpha mRNA and returned to baseline values 1 week later. This pattern of response was also observed, albeit minimised, in patients exercising below the LT. Conclusions In patients with COPD, exercise enhances the decrease in mtDNA content of skeletal muscle and the expression of PGC-1 alpha mRNA seen in healthy subjects, probably due to oxidative stress.