Decreased exercise-induced expression of nuclear factor-κB-regulated genes in muscle of patients with COPD.
BACKGROUND
Nuclear factor (NF)-κB activation and oxidative stress are physiologic responses of skeletal muscle to exercise but may be impaired in patients with COPD. Therefore, we investigated NF-κB activity and expression of NF-κB-regulated genes in muscle of patients with COPD and control subjects before and after exercise.


METHODS
Quadriceps specimens were obtained before, immediately after, and 2 h after a submaximal cycle ergometry test from seven patients with COPD (50.6 ± 5.7 SEM FEV(1) of patients with COPD) and seven age-matched control subjects. NF-κB DNA-binding activity in muscle and peripheral blood mononuclear cells (PBMCs) was determined using electrophoretic mobility shift assay and enzyme-linked immunosorbent assay, respectively. mRNA expression and protein carbonylation were measured by real-time polymerase chain reaction and Western blot, respectively.


RESULTS
In control subjects, IL-6, IκBα, tumor necrosis factor-α, IL-1β, superoxide dismutase, thioredoxin, heme oxygenase 1, and heat shock protein-70 were upregulated in muscle after exercise, whereas in patients with COPD only IL-6 mRNA was increased. Exercise-induced antiapoptotic Bcl2 mRNA levels were attenuated in patients with COPD compared with control subjects. Basal muscle protein oxidation was higher in patients with COPD than in control subjects, but attenuated in response to exercise. No exercise-induced changes in NF-κB DNA-binding activity in muscle and PBMCs of either group were detected.


CONCLUSIONS
Skeletal muscle of patients with COPD is characterized by an impaired response to exercise of NF-κB-regulated genes encoding inflammatory cytokines, antioxidants, stress proteins, and survival factors.
Mercken
Evi M
EM
NUTRIM School for Nutrition, Toxicology and Metabolism, Department of Respiratory Medicine, Maastricht University Medical Centre+ (MUMC+), Maastricht, The Netherlands. Electronic address: e.mercken@pul.unimaas.nl.
Hageman
Geja J
GJ
Health Risk Analysis and Toxicology, Maastricht University Medical Centre+ (MUMC+), Maastricht, The Netherlands.
Langen
Ramon C
RC
NUTRIM School for Nutrition, Toxicology and Metabolism, Department of Respiratory Medicine, Maastricht University Medical Centre+ (MUMC+), Maastricht, The Netherlands.
Wouters
Emiel F
EF
NUTRIM School for Nutrition, Toxicology and Metabolism, Department of Respiratory Medicine, Maastricht University Medical Centre+ (MUMC+), Maastricht, The Netherlands; Centre for Integrated Rehabilitation Organ Failure, Horn, The Netherlands.
Schols
Annemie M
AM
NUTRIM School for Nutrition, Toxicology and Metabolism, Department of Respiratory Medicine, Maastricht University Medical Centre+ (MUMC+), Maastricht, The Netherlands.
D001706:Biopsy; D015153:Blotting, Western; D016022:Case-Control Studies; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005080:Exercise Test; D015870:Gene Expression; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012129:Respiratory Function Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D013482:Superoxide Dismutase / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D018840:HSP70 Heat-Shock Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013879:Thioredoxins; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D051550:I-kappa B Kinase