title: Effects of exercise on mitochondrial DNA content in skeletal muscle of patients with COPD.
abstract: 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 (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.
  
  
  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-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.
  
  
  CONCLUSIONS
  In 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.
authors.affiliation: Servicio de Neumología, Hospital General Universitario Gregorio Marañón, c/Doctor Ezquerdo 46, 28007 Madrid, Spain. lpuente.hgugm@salud.madrid.org
authors.forename: Luis
authors.initials: L
authors.lastname: Puente-Maestu
authors.forename: Alberto
authors.initials: A
authors.lastname: Lázaro
authors.forename: Alberto
authors.initials: A
authors.lastname: Tejedor
authors.forename: Sonia
authors.initials: S
authors.lastname: Camaño
authors.forename: Marta
authors.initials: M
authors.lastname: Fuentes
authors.forename: Miguel
authors.initials: M
authors.lastname: Cuervo
authors.forename: Beatriz Oláiz
authors.initials: BO
authors.lastname: Navarro
authors.forename: Alvar
authors.initials: A
authors.lastname: Agustí
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000378:metabolism*; D015444:Exercise / Q000502:physiology*; D006801:Humans; D019344:Lactic Acid / Q000096:biosynthesis; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics; D010101:Oxygen Consumption / Q000502:physiology; D016133:Polymerase Chain Reaction / Q000379:methods; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013147:Spirometry / Q000379:methods
chemical_list: D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D019344:Lactic Acid