{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:26:08Z","timestamp":1791257168718,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2002,8,1]],"date-time":"2002-08-01T00:00:00Z","timestamp":1028160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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\u2013modified 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 &amp;lt; 70% predicted) or without COPD (n = 12; FEV1 &amp;gt; 84% predicted) who had undergone lung resection. As 4-HNE and transforming growth factor-\u03b21 (TGF-\u03b21) can modulate \u03b3-glutamylcysteine synthetase (\u03b3-GCS) mRNA levels in lung cells, we assessed the relations between 4-HNE\u2013modified protein levels, FEV1, \u03b3-GCS, and TGF-\u03b21. 4-HNE\u2013modified 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 &amp;lt; 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 &amp;lt; 0.05) and a positive correlation between 4-HNE adducts and TGF-\u03b21 protein and mRNA as well as \u03b3-GCS mRNA levels in airway and alveolar epithelium (p &amp;lt; 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.<\/jats:p>","DOI":"10.1164\/rccm.2110101","type":"journal-article","created":{"date-parts":[[2002,10,1]],"date-time":"2002-10-01T17:37:17Z","timestamp":1033493837000},"page":"490-495","source":"Crossref","is-referenced-by-count":384,"title":["4-Hydroxy-2-Nonenal, a Specific Lipid Peroxidation Product, Is Elevated in Lungs of Patients with Chronic Obstructive Pulmonary Disease"],"prefix":"10.1093","volume":"166","author":[{"given":"Irfan","family":"Rahman","sequence":"first","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemarie A. M.","family":"van Schadewijk","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann J. L.","family":"Crowther","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter S.","family":"Hiemstra","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Stolk","sequence":"additional","affiliation":[{"name":"Respiratory Medicine Unit, ELEGI Laboratory, University of Edinburgh Medical School, Edinburgh, United Kingdom; Department of 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