NF-kappaB activation and iNOS upregulation in skeletal muscle of patients with COPD and low body weight.
BACKGROUND
Weight loss, mostly due to skeletal muscle atrophy, is a frequent and clinically relevant problem in patients with chronic obstructive pulmonary disease (COPD). The molecular mechanisms underlying this phenomenon are unclear. This study sought to investigate whether activation of the nuclear transcription factor NF-kappaB and upregulation of the inducible form of nitric oxide synthase (iNOS) occur in the skeletal muscle of patients with COPD and low body weight as potential molecular mechanisms leading to cachexia


METHODS
NF-kappaB DNA binding activity was determined by electromobility shift assay and the immunoreactivity of its inhibitory subunit IkappaB-kappa and that of iNOS by Western blot analysis in biopsy specimens of the quadriceps femoris muscle of seven COPD patients with normal body mass index (BMI, 27.5 (1) kg/m(2)) and seven patients with low BMI (18.5 (1) kg/m(2)).


RESULTS
Compared with patients with normal body weight, those with low BMI showed a 30% increase in NF-kappaB DNA binding activity, a lower expression of IkappaB-alpha (3.37 (0.47) IOD v 5.96 (0.75) IOD, p<0.05; mean difference 2.59; 95% CI -4.53 to -0.65) and higher iNOS expression (1.51 (0.29) IOD v 0.78 (0.11) IOD, p<0.05; mean difference 0.74; 95% CI 0.04 to 1.42).


CONCLUSIONS
NF-kappaB activation and iNOS induction occur in skeletal muscle of COPD patients with low body weight. These changes might contribute to the molecular pathogenesis of cachexia in COPD.
Agustí
A
A
Servei de Pneumologia, Hospital Universitari Son Dureta & Institut Universitari d'Investigacions en Ciencies de la Salut (IUNICS), Palma de Mallorca, Spain. aagusti@hsd.es
Morlá
M
M
Sauleda
J
J
Saus
C
C
Busquets
X
X
D015992:Body Mass Index; D001835:Body Weight; D006801:Humans; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D015854:Up-Regulation
D016328:NF-kappa B; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II