title: MAPK signaling in the quadriceps of patients with chronic obstructive pulmonary disease.
abstract: Muscle atrophy in chronic obstructive pulmonary disease (COPD) is associated with reduced exercise tolerance, muscle strength, and survival. The molecular mechanisms leading to muscle atrophy in COPD remain elusive. The mitogen-activated protein kinases (MAPKs) such as p38 MAPK and ERK 1/2 can increase levels of MAFbx/Atrogin and MuRF1, which are specifically involved in muscle protein degradation and atrophy. Our aim was to investigate the level of activation of p38 MAPK, ERK 1/2, and JNK in the quadriceps of patients with COPD. A biopsy of the quadriceps was obtained in 18 patients with COPD as well as in 9 healthy controls. We evaluated the phosphorylated as well as total protein levels of p38 MAPK, ERK 1/2, and JNK as well as MAFbx/Atrogin and MuRF1 in these muscle samples. The corresponding mRNA expression was also assessed by RT-PCR. Ratios of phosphorylated to total level of p38 MAPK (P = 0.02) and ERK 1/2 (P = 0.01) were significantly elevated in patients with COPD compared with controls. Moreover, protein levels of MAFbx/Atrogin showed a tendency to be greater in patients with COPD (P = 0.08). mRNA expression of p38 MAPK (P = 0.03), ERK 1/2 (P = 0.02), and MAFbx/Atrogin (P = 0.04) were significantly elevated in patients with COPD. In addition, phosphorylated-to-total p38 MAPK ratio (Pearson's r = -0.45; P < 0.05) and phosphorylated-to-total ERK 1/2 ratio (Pearson's r = -0.47; P < 0.05) were negatively associated with the mid-thigh muscle cross-sectional area. These data support the hypothesis that the MAPKs might play a role in the development of muscle atrophy in COPD.
authors.affiliation: Centre de recherche, Institut Universitaire de cardiologie et de pneumologie de Québec, Université Laval, Quebec, Canada.
authors.forename: Bruno B
authors.initials: BB
authors.lastname: Lemire
authors.forename: Richard
authors.initials: R
authors.lastname: Debigaré
authors.forename: Annie
authors.initials: A
authors.lastname: Dubé
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Thériault
authors.forename: Claude H
authors.initials: CH
authors.lastname: Côté
authors.forename: François
authors.initials: F
authors.lastname: Maltais
mesh_terms: D000368:Aged; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009124:Muscle Proteins / Q000032:analysis / Q000378:metabolism; D009133:Muscular Atrophy / Q000378:metabolism; D010766:Phosphorylation; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology*; D052097:Quadriceps Muscle / Q000201:enzymology* / Q000473:pathology; D044843:SKP Cullin F-Box Protein Ligases / Q000032:analysis; D013848:Thigh / Q000503:physiopathology; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000032:analysis
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; D020928:Mitogen-Activated Protein Kinases