American Journal of Respiratory and Critical Care Medicine Vol 166. pp. 490-495, (2002)
© 2002 American Thoracic Society
4-Hydroxy-2-Nonenal, a Specific Lipid Peroxidation Product, Is Elevated in Lungs of Patients with Chronic Obstructive Pulmonary Disease
Irfan Rahman,
Annemarie A. M. van Schadewijk,
Ann J. L. Crowther,
Pieter S. Hiemstra,
Jan Stolk,
William MacNee and
Willem I. De Boer
Respiratory Medicine Unit, ELEGI Laboratory, University of Edinburgh Medical School, Edinburgh, United Kingdom; Department of Pulmonology, Leiden University Medical Centre, Leiden; and Department of Pulmonology, Erasmus University, Rotterdam, The Netherlands
Correspondence and requests for reprints should be addressed to Dr. I. Rahman, ELEGI Laboratory, Respiratory Medicine Unit, University of Edinburgh Medical School, Wilkie Building, Teviot Place, Edinburgh EH8 9AG, UK. E-mail: irfan.rahman{at}ed.ac.uk
Cigarette smoking results in oxidative stress and inflammation in the lungs, which are involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). 4-Hydroxy-2-nonenal (4-HNE), a highly reactive diffusible product of lipid peroxidation, is a key mediator of oxidant-induced cell signaling and apoptosis. 4-HNE has a high affinity toward cysteine, histidine, and lysine groups and forms direct protein adducts. We investigated the presence of 4-HNE–modified proteins in lung tissue obtained from subjects with and without COPD. We studied 23 current or ex-smokers with similar smoking histories with COPD (n = 11; FEV1 < 70% predicted) or without COPD (n = 12; FEV1 > 84% predicted) who had undergone lung resection. As 4-HNE and transforming growth factor-ß1 (TGF-ß1) can modulate  -glutamylcysteine synthetase (-GCS) mRNA levels in lung cells, we assessed the relations between 4-HNE–modified protein levels, FEV1, -GCS, and TGF-ß1. 4-HNE–modified protein levels were elevated in airway and alveolar epithelial cells, endothelial cells, and neutrophils in subjects with COPD, compared with the levels in subjects without COPD (p < 0.01). We also observed a significant inverse correlation between the levels of 4-HNE adducts in alveolar epithelium, airway endothelium, and neutrophils and FEV1 (p < 0.05) and a positive correlation between 4-HNE adducts and TGF-ß1 protein and mRNA as well as -GCS mRNA levels in airway and alveolar epithelium (p < 0.01). The elevated levels of 4-HNE may play a role in the signaling events in lung inflammation leading to the imbalance of the expression of both proinflammatory mediators and protective antioxidant genes in COPD.
Key Words: 4-hydroxy-2-nonenal • glutathione • transforming growth factor-ß1 • lungs • chronic obstructive pulmonary disease
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