Oxidative stress may differentially regulate
protein loss within peripheral muscles of severe
chronic obstructive pulmonary disease (
COPD) patients exhibiting different body composition. Oxidation levels of
proteins,
myosin heavy chain (MyHC) and myonuclei,
superoxide anion,
antioxidants, actin,
creatine kinase, carbonic anhydrase-3,
ubiquitin-
proteasome system, redox-signalling pathways,
inflammation and muscle structure, and damage were quantified in limb muscles of severe
COPD patients with and without muscle wasting, and in sedentary controls. Compared with controls, in the quadriceps of muscle-wasted
COPD patients, levels of protein carbonylation, oxidation of MyHC and myonuclei,
superoxide anion production,
superoxide dismutase, total
protein ubiquinitation, E2(14k), atrogin-1, FoxO1 and p65 were higher, while content of MyHC,
creatine kinase, carbonic anhydrase-3,
myogenin, and fast-twitch fibre size were decreased. Importantly, in nonwasted
COPD patients, where MyHC was more oxidised than in controls, its content was preserved. Muscle
inflammation and
glutathione levels did not differ between patients and controls. In all patients, muscle structure abnormalities were increased, while muscle force and exercise capacity were reduced. In severe
COPD, while muscle oxidative stress increases regardless of their body composition,
protein ubiquitination and loss of MyHC were enhanced only in patients exhibiting
muscle atrophy. Oxidative stress does not seem to directly modulate
muscle protein loss in these patients.