Background: Although exercise training has beneficial effects on skeletal muscle bioenergetics and exercise performance in patients with severe COPD, it may also be associated with increased quadriceps oxidative and nitrosative stress. Our aim was to explore quadriceps oxidative and nitrosative stress in severe COPD patients, both before and after a three-week endurance exercise program, and to identify the nature of the oxidatively modified proteins.
Methods: Reactive carbonyls, hydroxynonenal-protein adducts, antioxidant enzymes, nitric oxide synthases (NOS), and 3-nitrotyrosine levels were determined in the quadriceps (pre- and post-exercise) of 15 severe COPD patients and 7 healthy controls using immunoblotting (1-D and 2-D electrophoresis), activity assays, and mass spectrometry.
Results: At baseline, muscle levels of reactive carbonyls, which were negatively associated with muscle strength and exercise tolerance, were significantly higher in patients than in controls. Moreover, baseline hydroxynonenal-protein adducts, SOD activity, inducible NOS, and 3-nitrotyrosine immunoreactivity levels were also significantly increased in the quadriceps of the patients compared to controls. In the patients, chronic exercise induced a significant rise in iNOS levels and a four-fold increase in protein nitration. Chronic endurance exercise induced tyrosine nitration of muscle enolase 3,β, aldolase A, triosephosphate isomerase, creatine kinase, carbonic anhydrase III, myoglobin, and uracil DNA glycosylase in the quadriceps of the patients, while the contractile protein alpha-1 actin was nitrated only in patients exhibiting muscle loss (post-hoc analysis). Superoxide dismutase activity increased after the exercise program only in the controls.
Conclusions: In severe COPD, chronic endurance exercise induces increased tyrosine nitration of quadriceps proteins involved in glycolysis, energy distribution, carbon dioxide hydration, muscle oxygen transfer, DNA repair, and contractile function in patients exhibiting systemic effects of the disease.
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