Does oxidative stress modulate limb muscle atrophy in severe COPD patients?

Abstract

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, redoxsignalling 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.

Cachexia in chronic obstructive pulmonary disease: new insights and therapeutic perspective

“…Additionally, limb muscle NEDD4 protein expression is increased in patients with COPD 57. Total poly‐ubiquitinated protein is increased in limb muscles of COPD patients compared with healthy controls39, 56 and in cachectic COPD patients compared with non‐cachectic COPD patients 38…”

“…MURF1 limb and respiratory muscle mRNA and protein expression appear unaltered in COPD patients compared with controls,38, 40, 55, 56, 57 although one study reported increased MURF1 protein expression in the limb muscles of cachectic COPD patients 39. In COPD patients, MURF1 protein expression is relatively increased in limb muscle than in the respiratory muscle, while this difference was not found in controls 46.…”

“…NF‐κB activity is increased in COPD patients compared with controls38, 39 and in cachectic COPD patients compared with non‐cachectic COPD patients 38, 40. Furthermore, limb muscle NF‐κB activity is increased in patients with lung cancer cachexia 41.…”

“…Furthermore, cachectic COPD patients show increased limb muscle mRNA expression of MURF1 compared with a control population 44. ATROGIN1 mRNA and protein expression are increased in limb muscles,38, 39, 40, 44, 56, 57 but unaltered in respiratory muscles of patients with COPD 55. Similarly, ATROGIN1 mRNA expression is increased in the limb muscles of smokers 58.…”

“…Furthermore, Myogenin (MYOG) mRNA expression is unaltered in COPD patients 57. However, in cachectic COPD patients, MYOD140 and MYOG38, 39 protein expression are reduced compared with controls, while no alteration in MYOG protein expression was found in the limb muscles of cachectic compared with non‐cachectic COPD patients 38. It should be considered that in different populations and disease stages, the course of the satellite cell response might be altered, which may have implications for the timing of the measurements.…”