Oxidized proteins and superoxide anion production in the diaphragm of severe COPD patients

¹ Muscle Research and Respiratory System Unit, Respiratory Medicine and Thoracic Surgery Depts, IMIM-Hospital del Mar, Centro de Investigación en Red de Enfermedades Respiratorias (CibeRes), Health and Experimental Sciences Dept (CEXS), Universitat Pompeu Fabra, and Universitat Autònoma de Barcelona, PRBB, Dr. Aiguader, 88, Barcelona, Catalonia, E-08003 Spain
² Critical Care and Respiratory Divisions, Royal Victoria Hospital and Meakins-Christie Laboratories, McGill University, 687, Pine Avenue west, Montreal, Quebec, H3A 1A1 Canada

^* To whom correspondence should be addressed. E-mail: ebarreiro{at}imim.es.

	Abstract

In the diaphragms of COPD patients, the nature of the oxidatively modified proteins and superoxide anion production were explored.

Diaphragm specimens were obtained through thoracotomy because of localized lung lesions in COPD patients (sixteen severe and eight moderate) and ten control subjects. Lung and respiratory muscle functions were evaluated. Oxidized 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 to controls: respiratory muscle function was impaired; creatine kinase, carbonic anhydrase III, actin and myosin were oxidized; 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 superoxide anion was increased in the diaphragms of these patients.

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