4-Hydroxy-2-nonenal, a specific lipid peroxidation product, is elevated in lungs of patients with chronic obstructive pulmonary disease

Am J Respir Crit Care Med. 2002 Aug 15;166(4):490-5. doi: 10.1164/rccm.2110101.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / analysis*
  • Aldehydes / metabolism*
  • Apoptosis
  • Case-Control Studies
  • Disease Progression
  • Forced Expiratory Volume
  • Humans
  • Immunohistochemistry
  • Inflammation
  • Lipid Peroxidation / physiology*
  • Lung / chemistry*
  • Macrophages, Alveolar / physiology
  • Middle Aged
  • Neutrophils / physiology
  • Oxidative Stress / physiology
  • Pulmonary Disease, Chronic Obstructive / etiology*
  • Pulmonary Disease, Chronic Obstructive / metabolism*
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Severity of Illness Index
  • Signal Transduction
  • Smoking / adverse effects*
  • Smoking / metabolism*
  • Smoking / pathology


  • Aldehydes
  • 4-hydroxy-2-nonenal