Article Text

Download PDFPDF

Original article
Effects of exercise on mitochondrial DNA content in skeletal muscle of patients with COPD
  1. Luis Puente-Maestu1,2,
  2. Alberto Lázaro3,
  3. Alberto Tejedor3,
  4. Sonia Camaño3,
  5. Marta Fuentes1,2,
  6. Miguel Cuervo4,
  7. Beatriz Oláiz Navarro5,
  8. Alvar Agustí6,7
  1. 1Servicio de Neumología, Hospital General Universitario Gregorio Marañón, Madrid, Spain
  2. 2Universidad Complutense de Madrid, Madrid, Spain
  3. 3Laboratorio de Nefrología Experimental, Hospital General Universitario Gregorio Marañón, Universidad Complutense de Madrid, Madrid, Spain
  4. 4Servicio de Traumatología, Hospital General Universitario Gregorio Marañón; Universidad Complutense de Madrid, Madrid, Spain
  5. 5Servicio de Cirugía de Tórax, Hospital General Universitario de Getafe, Madrid, Spain
  6. 6Institut del Torax, Hospital Clínic, IDIBAPS, Barcelona, Spain
  7. 7CIBER Enfermedades Respiratorias (CIBERES) y Fundación Caubet-Cimera, Mallorca, Spain
  1. Correspondence to Luis Puente-Maestu, Servicio de Neumología, Hospital General Universitario Gregorio Marañón, c/Doctor Ezquerdo 46, 28007 Madrid, Spain; lpuente.hgugm{at}salud.madrid.org

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.

  • DNA damage, mitochondria biogenesis, oxidative stress, peroxisome proliferator-activated receptor-γ
  • coactivator-1α, quadriceps muscle injury, superoxide dismutase
  • COPD mechanisms
  • exercise
  • oxidative stress
  • pulmonary rehabilitation
View Full Text

Statistics from Altmetric.com

Footnotes

  • Funding Supported by Fondo de Investigaciones Sanitarias (PS09/02391).

  • Competing interests None.

  • Patient consent All participants gave written informed consent after being made fully aware of the goals and potential risks of the study.

  • Ethics approval This study was conducted with the approval of the Committee for Ethics in Human Research of Madrid Sanitary Area 1 and all aspects of the study comply with the Declaration of Helsinki.

  • Provenance and peer review Not commissioned; externally peer reviewed.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.