Oxidative and nitrosative stress in the diaphragm of patients with COPD

Hanneke JH Wijnhoven¹, Leo MA Heunks¹, Maartje CP Geraedts¹, Theo Hafmans², José R Viña³, PN Richard Dekhuijzen¹

¹Department of Pulmonary Diseases and Institute for Fundamental and Clinical Human Movement Sciences, and ²Department of Matrix Biochemistry, Radboud University Nijmegen Medical Centre, The Netherlands; ³Department of Physiology, Faculty of Medicine, University of Valencia, Spain

Abstract: COPD is associated with an increased load on the diaphragm. Since chronic muscle loading results in changes in antioxidant capacity and formation of reactive oxygen and reactive nitrogen species, we hypothesized that COPD has a similar effect on the diaphragm, which is related to the severity of COPD. Catalase activity was determined spectrophotometrically. Levels of 4-hydroxy-2-nonenal (HNE)-protein adducts and 3-nitrotyrosine (NT) formation were measured using western blotting. Levels of malondialdehyde (MDA) were assessed by high-performance liquid chromatography. We found that catalase activity was ~89% higher in the diaphragm of severe COPD patients (FEV₁ 37 ± 5% predicted) compared with non-COPD patients. MDA levels, a marker for lipid peroxidation, were significantly lower in the diaphragm of COPD patients compared with non-COPD patients, whereas the level of HNE-protein adducts was equal in both groups. NT formation was not different between groups. However, increasing hyperinflation and NT formation were inversely correlated. These results indicate that in COPD the diaphragm adapts to a higher work load by increasing catalase activity, resulting in a reduction in oxidative damage to lipids and tyrosine nitration of proteins.

 

Keywords: COPD, respiratory muscles, oxidants, NO, antioxidants