title: p38 mitogen-activated protein kinase is not activated in the quadriceps of patients with stable chronic obstructive pulmonary disease.
abstract: Quadriceps weakness is associated with a poor prognosis in COPD. Several data suggest that immobility and muscle wasting may be related through up-regulation of the p38 Mitogen associated protein kinase (MAPK) signalling pathway. We therefore hypothesised that this might occur in the quadriceps of COPD patients. We studied 105 stable COPD outpatients (mean FEV(1) 43.9% predicted) and 27 age and gender matched controls. We measured fat-free mass, quadriceps strength and daily physical activity using triaxial accelerometry. A quadriceps biopsy was obtained in which components of the p38-MAPK signalling pathway were examined. Patients had reduced fat-free mass index (16.1 (2.2) kg/m(2) vs 17.2 (2.2) kg/m(2), p = 0.02) and exhibited quadriceps weakness (mean (SD) maximal voluntary contraction force 72.1% (18.7) predicted and 82.3% (7.1) predicted for patients and controls respectively, p = 0.01). Physical activity was significantly reduced in the patient group; in particular mean (SD) locomotion time was 101 (48) minutes/12 hours in controls and 48 (31) minutes in patients (p < 0.0001). However, in biopsies obtained from these patients, no differences were observed for total or phosphorylated HSP27 or p38 MAPK protein or p38 MAPK mRNA (MAPK14); of the downstream products both GADD45β and c-jun mRNA were reduced in COPD patients while c-myc was not different from controls. No parameter correlated with physiological data within the patient group. We conclude that, despite the presence of reduced fat-free mass, quadriceps weakness and inactivity, p38 MAPK signalling was not up-regulated in skeletal muscle of stable out-patients with COPD.
authors.affiliation: Molecular Medicine, National Heart & Lung Institute, Imperial College, South Kensington Campus, London SW7 2AZ, United Kingdom.
authors.forename: Joanna
authors.initials: J
authors.lastname: Riddoch-Contreras
authors.forename: Tomasz
authors.initials: T
authors.lastname: George
authors.forename: Samantha A
authors.initials: SA
authors.lastname: Natanek
authors.forename: Gemma S
authors.initials: GS
authors.lastname: Marsh
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Hopkinson
authors.forename: Ruth
authors.initials: R
authors.lastname: Tal-Singer
authors.forename: Paul
authors.initials: P
authors.lastname: Kemp
authors.forename: Michael I
authors.initials: MI
authors.lastname: Polkey
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology*; D018908:Muscle Weakness / Q000378:metabolism* / Q000503:physiopathology; D009133:Muscular Atrophy / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D052097:Quadriceps Muscle / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D048051:p38 Mitogen-Activated Protein Kinases