Journal
EUROPEAN RESPIRATORY JOURNAL
Volume 33, Issue 6, Pages 1309-1319Publisher
EUROPEAN RESPIRATORY SOC JOURNALS LTD
DOI: 10.1183/09031936.00072008
Keywords
Chronic obstructive pulmonary disease; muscle compartments; oxidised proteins; respiratory muscles; superoxide anion
Categories
Funding
- FIS, the Spanish Health Ministry [04/00161, 06/1043]
- SEPAR 2004, the Catalan Government [2005-SGRO1060]
- CIBERES (all Spain)
- ERS COPD
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In the diaphragms of chronic obstructive pulmonary disease (COPD) patients, the nature of oxidatively modified proteins and superoxide anion production were explored. Diaphragm specimens were obtained through thoracotomy because of localised lung lesions in COPD patients (16 severe and eight moderate) and 10 control subjects. Lung and respiratory muscle functions were evaluated. Oxidised proteins were identified using immunoblotting and mass spectrometry. Protein and activity levels of the identified proteins were determined using immunoblotting and activity assays. Lucigenin-derived chemiluminescence signals in a luminometer were used to determine superoxide anion levels in muscle compartments (mitochondria, membrane and cytosol) using selective inhibitors. In severe COPD patients compared with controls, respiratory muscle function was impaired, creatine kinase, carbonic anhydrase III, actin and myosin were oxidised; myosin carbonylation levels were increased five-fold; creatine kinase content and activity and myosin protein were reduced; superoxide anion levels were increased in both mitochondria and membrane compartments; and the percentage of superoxide anion inhibition achieved by rotenone was significantly greater. In severe COPD patients, oxidation of diaphragm proteins involved in energy production and contractile performance is likely to partially contribute to the documented respiratory muscle dysfunction. Furthermore, generation of the superoxide anion was increased in the diaphragms of these patients.
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