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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2002-8-20
pubmed:abstractText
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; FEV(1) < 70% predicted) or without COPD (n = 12; FEV(1) > 84% predicted) who had undergone lung resection. As 4-HNE and transforming growth factor-beta(1) (TGF-beta(1)) can modulate gamma-glutamylcysteine synthetase (gamma-GCS) mRNA levels in lung cells, we assessed the relations between 4-HNE-modified protein levels, FEV(1), gamma-GCS, and TGF-beta(1). 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 FEV(1) (p < 0.05) and a positive correlation between 4-HNE adducts and TGF-beta(1) protein and mRNA as well as gamma-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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1073-449X
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
166
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
490-5
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12186826-Aldehydes, pubmed-meshheading:12186826-Apoptosis, pubmed-meshheading:12186826-Case-Control Studies, pubmed-meshheading:12186826-Disease Progression, pubmed-meshheading:12186826-Forced Expiratory Volume, pubmed-meshheading:12186826-Humans, pubmed-meshheading:12186826-Immunohistochemistry, pubmed-meshheading:12186826-Inflammation, pubmed-meshheading:12186826-Lipid Peroxidation, pubmed-meshheading:12186826-Lung, pubmed-meshheading:12186826-Macrophages, Alveolar, pubmed-meshheading:12186826-Middle Aged, pubmed-meshheading:12186826-Neutrophils, pubmed-meshheading:12186826-Oxidative Stress, pubmed-meshheading:12186826-Pulmonary Disease, Chronic Obstructive, pubmed-meshheading:12186826-Severity of Illness Index, pubmed-meshheading:12186826-Signal Transduction, pubmed-meshheading:12186826-Smoking
pubmed:year
2002
pubmed:articleTitle
4-Hydroxy-2-nonenal, a specific lipid peroxidation product, is elevated in lungs of patients with chronic obstructive pulmonary disease.
pubmed:affiliation
Respiratory Medicine Unit, ELEGI Laboratory, University of Edinburgh Medical School, Wilkie Building, Teviot Place, Edinburgh EH8 9AG, Scotland, UK. irfan.rahman@ed.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't