Published ahead of print on September 15, 2005, doi:10.1165/rcmb.2005-0114OC
© 2005 American Thoracic Society DOI: 10.1165/rcmb.2005-0114OC Expression and Carbonylation of Creatine Kinase in the Quadriceps Femoris Muscles of Patients with Chronic Obstructive Pulmonary DiseaseCritical Care and Respiratory Divisions, Royal Victoria Hospital and Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada; Muscle and Respiratory System Research Unit and Experimental Health Sciences Department, Institut Municipal d'Investigació Mèdica–Universitat Pompeu Fabra, Respiratory Medicine Department, Hospital del Mar, Barcelona, Catalonia, Spain Correspondence and requests for reprints should be addressed to Dr. S. Hussain, Room L3.05, 687 Pine Ave. West, Montreal, PQ, H3A 1A1 Canada. E-mail: sabah.hussain{at}muhc.mcgill.ca Oxidative protein modification involving carbonylation has recently been identified as an important factor in skeletal muscle dysfunction in patients with chronic obstructive pulmonary disease (COPD). However, the exact identity of modified proteins inside limb muscles of patients with COPD remains unknown. We used 2D electrophoresis, immunoblotting, and mass spectrometry to identify carbonylated proteins in the vastus lateralis muscle of 12 patients with COPD and 6 control subjects. Both creatine kinase (CK) and carbonic anhydrase III (CAIII) were identified as being strongly carbonylated in this muscle in both groups of subjects. Total CK activity, CK protein expression, and the intensity of CK carbonylation were significantly greater in the muscles of patients with COPD as compared with control subjects, whereas CAIII protein expression and intensity of carbonylation were similar in the two groups. In patients with COPD, CK activity and protein expression correlated positively with FEV1 and V·O2max, whereas the intensity of CK carbonylation correlated negatively with the same parameters. These results indicate that oxygen radicals selectively target CK and CAIII inside limb muscles of humans. The observation that the intensity of CK carbonylation correlates negatively with CK activity in limb muscles of patients with COPD suggests that carbonylation may have a deleterious effect on CK activity, and may contribute to impaired CK function in the limb muscles of these patients.
Key Words: carbonic anhydrase • COPD • creatine kinase • protein oxidation • skeletal muscle. This article has been cited by other articles:
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