Published ahead of print on May 3, 2007, doi:10.1164/rccm.200605-704OC
Am. J. Respir. Crit. Care Med., Volume 176, Number 3, August 2007, 261-269
A more recent version of this article appeared on August 1, 2007
Submitted on May 26, 2006
Accepted on May 3, 2007
Muscle Atrophy and Hypertrophy Signalling in Patients with Chronic Obstructive Pulmonary Disease
Marieve Doucet1, Aaron P Russell2, Bertrand Leger3, Richard Debigare1, Denis R Joanisse4, Marc-Andre Caron1, Pierre LeBlanc1, and Francois Maltais1*
1 Centre de recherche de l'Hopital Laval, Institut universitaire de cardiologie et de pneumologie de l'Universite Laval, Quebec, Canada,
2 Clinique Romande de Readaptation SUVA Care, Sion, Switzerland; Centre for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Melbourne, Australia,
3 Clinique Romande de Readaptation SUVA Care, Sion, Switzerland,
4 Division de Kinesiologie, Universite Laval, Quebec, Canada
* To whom correspondence should be addressed. E-mail: francois.maltais{at}med.ulaval.ca.
The molecular mechanisms of muscle atrophy in chronic obstructive pulmonary disease are poorly understood. In wasted animals, muscle mass is regulated by several AKT -
related signalling pathways.
Purposes: To measure the protein expression of AKT,
FoxO-1, -3, atrogin-1 and the phosphophrylated form of AKT, p70S6K GSK-3 and 4EBP1 and the mRNA expression of atrogin-1, MuRF1, FoxO-1,-3 in the quadriceps of 12 patients with chronic obstructive pulmonary disease with muscle atrophy and 10 healthy
controls. Five patients with chronic obstructive pulmonary disease with preserved muscle mass were subsequently recruited and were compared with 6 patients with low
muscle mass.
Methods: were measured the quadriceps by Western blot and quantitative PCR, respectively. Results: The levels of atrogin-1 and MuRF1 mRNA and of phosphorylated AKT and 4E-BP1 and FoxO-1 proteins were increased in chronic
obstructive pulmonary disease patients with muscle atrophy compared to healthy controls while atrogin-1, p70S6K, GSK-3 and FoxO-3 protein levels were similar. Chronic obstructive pulmonary disease patients with muscle atrophy showed an increased expression of p70S6K, GSK-3 and 4E-BP1 compared to chronic obstructive pulmonary disease patients with preserved muscle mass.
Conclusion: An increase in atrogin-1 and MuRF1 mRNA and FoxO-1 protein content was observed in the quadriceps chronic obstructive pulmonary disease patients. The transcriptional regulation of atrogin-1 and MuRF1 may occur via FoxO-1 but independently of AKT. The overexpression of the muscle hypertrophic signalling pathways found in chronic obstructive pulmonary disease patients with muscle atrophy could represent an attempt to restore muscle mass.
Key words: Chronic obstructive pulmonary disease, muscle wasting, AKT, FoxO-1, E3-ligases
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