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Am J Respir Crit Care Med. 2007 Aug 1;176(3):261-9. Epub 2007 May 3.

Muscle atrophy and hypertrophy signaling in patients with chronic obstructive pulmonary disease.

Author information

1
Centre de Recherche de l'Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie de l'Université Laval, Laval, Québec, Canada.

Abstract

RATIONALE:

The molecular mechanisms of muscle atrophy in chronic obstructive pulmonary disease (COPD) are poorly understood. In wasted animals, muscle mass is regulated by several AKT-related signaling pathways.

OBJECTIVES:

To measure the protein expression of AKT, forkhead box class O (FoxO)-1 and -3, atrogin-1, the phosphophrylated form of AKT, p70(S6K) glycogen synthase kinase-3beta (GSK-3beta), eukaryotic translation initiation factor 4E binding protein-1 (4E-BP1), and the mRNA expression of atrogin-1, muscle ring finger (MuRF) protein 1, and FoxO-1 and -3 in the quadriceps of 12 patients with COPD with muscle atrophy and 10 healthy control subjects. Five patients with COPD with preserved muscle mass were subsequently recruited and were compared with six patients with low muscle mass.

METHODS:

Protein contents and mRNA expression were measured by Western blot and quantitative polymerase chain reaction, respectively.

MEASUREMENTS AND MAIN RESULTS:

The levels of atrogin-1 and MuRF1 mRNA, and of phosphorylated AKT and 4E-BP1 and FoxO-1 proteins, were increased in patients with COPD with muscle atrophy compared with healthy control subjects, whereas atrogin-1, p70(S6K), GSK-3beta, and FoxO-3 protein levels were similar. Patients with COPD with muscle atrophy showed an increased expression of p70(S6K), GSK-3beta, and 4E-BP1 compared with patients with COPD with preserved muscle mass.

CONCLUSIONS:

An increase in atrogin-1 and MuRF1 mRNA and FoxO-1 protein content was observed in the quadriceps of patients with COPD. The transcriptional regulation of atrogin-1 and MuRF1 may occur via FoxO-1, but independently of AKT. The overexpression of the muscle hypertrophic signaling pathways found in patients with COPD with muscle atrophy could represent an attempt to restore muscle mass.

PMID:
17478621
DOI:
10.1164/rccm.200605-704OC
[Indexed for MEDLINE]

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