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

被引:171
|
作者
Doucet, Marieve
Russell, Aaron P.
Leger, Bertrand
Debigare, Richard
Joanisse, Denis R.
Caron, Marc-Andre
LeBlanc, Pierre
Maltais, Francois
机构
[1] Univ Laval, Hop Laval, Ctr Rech, Inst Cardiol & Pneumol, Quebec City, PQ G1K 7P4, Canada
[2] Clin Romande Readaptat SUV Care, Sion, Switzerland
[3] Deakin Univ, Sch Execise & Nutr Sci, Ctr Phys Act & Nutr, Melbourne, Vic, Australia
[4] Univ Laval, Div Kinesiol, Laval, PQ, Canada
关键词
chronic obstructive pulmonary disease; muscle wasting; AKT; forkhead box class O-1; E3-ligases;
D O I
10.1164/rccm.200605-704OC
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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 0 (FoxO)-1 and -3, atrogin-1, the phosphophrylated form of AKT, p70(S6K) glycogen synthase kinase-3 beta (GSK-3 beta), 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, p70s(S6K), GSK-3 beta, and FoxO-3 protein levels were similar. Patients with COPD with muscle atrophy showed an increased expression of p70(S6K), GSK-3 beta, 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 ma 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.
引用
收藏
页码:261 / 269
页数:9
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