Atrophy and hypertrophy signalling of the quadriceps and diaphragm in COPD.
BACKGROUND
Factors involved in the regulation of muscle mass in chronic obstructive pulmonary disease (COPD) are still poorly understood. Comparing the signalisation involved in muscle mass regulation between two muscles with different levels of activation within the same subjects is an interesting strategy to tease out the impact of local (muscle activity) versus systemic factors in the regulation of muscle mass. A study was undertaken to measure and compare the protein levels of p-AKT, AKT, Atrogin-1, p-p70S6K, p-4E-BP1, p-GSK3β as well as the mRNA expression of Atrogin-1, MuRF1 and FoxO-1 in the quadriceps and the diaphragm of 12 patients with COPD and 7 controls with normal lung function.


METHODS
Diaphragm biopsies were obtained during thoracic surgery and quadriceps samples were obtained from needle biopsies. Protein content and mRNA expression were measured by western blot and quantitative PCR, respectively.


RESULTS
Increased mRNA expressions of Atrogin-1, MuRF1 and FoxO-1 were found in the quadriceps compared with the diaphragm only in patients with COPD. The quadriceps/diaphragm ratio for MuRF1 was higher in COPD. The protein level of p-p70S6K was decreased in the quadriceps compared with the diaphragm in patients with COPD. The quadriceps/diaphragm ratios of p-p70S6K and p-GSK3β were lower in patients with COPD than in controls.


CONCLUSIONS
These results indicate a greater susceptibility to a catabolic/anabolic imbalance favouring muscle atrophy in the quadriceps compared with the diaphragm in patients with COPD. The balance between the atrophy and hypertrophy signalling is inhomogeneous between respiratory and lower limb muscles, suggesting that local factors are likely to be involved in the regulation of muscle mass in COPD.
Doucet
Mariève
M
Centre de recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Canada.
Dubé
Annie
A
Joanisse
Denis R
DR
Debigaré
Richard
R
Michaud
Annie
A
Paré
Marie-Ève
MÈ
Vaillancourt
Rosaire
R
Fréchette
Eric
E
Maltais
François
F
D000368:Aged; D001706:Biopsy; D003964:Diaphragm / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D006984:Hypertrophy / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics; D009133:Muscular Atrophy / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D052097:Quadriceps Muscle / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D014797:Vital Capacity / Q000502:physiology
D009124:Muscle Proteins; D012333:RNA, Messenger