title: MuRF-1 and atrogin-1 protein expression and quadriceps fiber size and muscle mass in stable patients with COPD.
abstract: BACKGROUND
  Animal studies demonstrate the importance of the E3 ubiquitin ligases, Muscle RING-Finger Protein 1 (MuRF-1) and atrogin-1, in muscle protein degradation during acute muscle atrophy. Small clinical studies suggest MuRF-1 and atrogin-1 expression in the quadriceps muscle is also increased in stable patients with Chronic Obstructive Pulmonary Disease compared to controls. However, it remains unclear whether these ligases have a role in maintaining a muscle-wasted state in COPD patients.
  
  
  METHODS
  32 stable COPD patients (16 with a low fat-free mass index (FFMI), 16 with a normal FFMI) and 15 controls underwent lung function and quadriceps strength tests and a percutaneous quadriceps biopsy. Quadriceps MuRF-1 and atrogin-1 protein were quantified with western blotting. Quadriceps fiber cross-sectional area (CSA) and fiber proportions were determined by immunohistochemistry on muscle sections. MuRF-1 and atrogin-1 levels were compared between COPD patients with and without a low FFMI, and between patients and controls, and correlations between MuRF-1 and atrogin-1 levels and quadriceps fiber CSA in the patients were investigated.
  
  
  RESULTS
  Atrogin-1 protein levels were lower in patients than controls, but similar in patients with a low and normal FFMI. MuRF-1 levels did not differ between any groups. MuRF-1 and atrogin-1 levels were not associated with quadriceps fiber CSA or quadriceps strength in patients.
  
  
  CONCLUSIONS
  Chronic upregulation of ubiquitin ligases was not evident in the quadriceps muscle of stable COPD patients with a low muscle mass. This does not exclude the possibility of transient increases in ubiquitin ligases during acute catabolic episodes.
authors.affiliation: 1Department of Respiratory Medicine, NIHR Respiratory Biomedical Research Unit of the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London , London , United Kingdom.
authors.forename: Samantha A
authors.initials: SA
authors.lastname: Natanek
authors.forename: Joanna
authors.initials: J
authors.lastname: Riddoch-Contreras
authors.forename: Gemma S
authors.initials: GS
authors.lastname: Marsh
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Hopkinson
authors.forename: John
authors.initials: J
authors.lastname: Moxham
authors.forename: William D-C
authors.initials: WD
authors.lastname: Man
authors.forename: Paul R
authors.initials: PR
authors.lastname: Kemp
authors.forename: Michael I
authors.initials: MI
authors.lastname: Polkey
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000473:pathology*; D009124:Muscle Proteins / Q000378:metabolism*; D009133:Muscular Atrophy / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D009929:Organ Size; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D052097:Quadriceps Muscle / Q000201:enzymology* / Q000473:pathology; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism*; D012720:Severity of Illness Index; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; C440907:FBXO32 protein, human; D044843:SKP Cullin F-Box Protein Ligases; C440908:TRIM63 protein, human; D044767:Ubiquitin-Protein Ligases