MuRF-1 and Atrogin-1 Protein Expression and Quadriceps Fiber Size and Muscle Mass in Stable Patients with COPD

Abstract

INTRODUCTION 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.

DOI: 10.3109/15412555.2013.781577
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@inproceedings{Natanek2013MuRF1AA, title={MuRF-1 and Atrogin-1 Protein Expression and Quadriceps Fiber Size and Muscle Mass in Stable Patients with COPD}, author={Samantha Amanda Natanek and Joanna Riddoch-Contreras and Gemma Sarah Marsh and Nicholas Stephen Hopkinson and John Moxham and William D.-C. Man and Paul R Kemp and Michael Iain Polkey}, booktitle={COPD}, year={2013} }