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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|
|
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104(33):
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|
|
|
|
|
|
|
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87(3):
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|
|
|
|
|
|
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[PDF]
|
|
|
|
|
|
|
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35(1):
111 - 115.
[Abstract]
[PDF]
|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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Redox Regulation of 4-Hydroxy-2-nonenal-mediated Endothelial Barrier Dysfunction by Focal Adhesion, Adherens, and Tight Junction Proteins
J. Biol. Chem.,
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281(46):
35554 - 35566.
[Abstract]
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|
|
|
|
|
|
|
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174(5):
490 - 491.
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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174(5):
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|
|
|
|
|
|
|
R. M. Tuder, T. Yoshida, W. Arap, R. Pasqualini, and I. Petrache
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3(6):
503 - 510.
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[PDF]
|
|
|
|
|
|
|
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Oxidative stress and redox regulation of lung inflammation in COPD.
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July 1, 2006;
28(1):
219 - 242.
[Abstract]
[Full Text]
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|
|
|
|
|
|
|
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July 1, 2006;
291(1):
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|
|
|
|
|
|
|
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291(1):
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|
|
|
|
|
|
|
K Nagai, T Betsuyaku, T Kondo, Y Nasuhara, and M Nishimura
Long term smoking with age builds up excessive oxidative stress in bronchoalveolar lavage fluid
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61(6):
496 - 502.
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|
|
|
|
|
|
|
I. Dalle-Donne, R. Rossi, R. Colombo, D. Giustarini, and A. Milzani
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April 1, 2006;
52(4):
601 - 623.
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|
|
|
|
|
|
|
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623 - 631.
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|
|
|
|
|
|
|
H. M. Ochs-Balcom, B. J. B. Grant, P. Muti, C. T. Sempos, J. L. Freudenheim, R. W. Browne, M. Trevisan, L. Iacoviello, P. A. Cassano, and H. J. Schunemann
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[Full Text]
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|
|
|
|
|
|
|
W. MacNee
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|
|
|
|
|
|
|
I. M. Adcock and K. Ito
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2(4):
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|
|
|
|
|
|
|
R. D. Wang, J. L. Wright, and A. Churg
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October 1, 2005;
33(4):
387 - 393.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. MacNee
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September 1, 2005;
14(94):
12 - 22.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Barnes and R. A. Stockley
COPD: current therapeutic interventions and future approaches
Eur. Respir. J.,
June 1, 2005;
25(6):
1084 - 1106.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Yasuda, M. Yamaya, K. Nakayama, S. Ebihara, T. Sasaki, S. Okinaga, D. Inoue, M. Asada, M. Nemoto, and H. Sasaki
Increased Arterial Carboxyhemoglobin Concentrations in Chronic Obstructive Pulmonary Disease
Am. J. Respir. Crit. Care Med.,
June 1, 2005;
171(11):
1246 - 1251.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Voelkel and L. Taraseviciene-Stewart
Emphysema: An Autoimmune Vascular Disease?
Proceedings of the ATS,
April 1, 2005;
2(1):
23 - 25.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. MacNee
Pulmonary and Systemic Oxidant/Antioxidant Imbalance in Chronic Obstructive Pulmonary Disease
Proceedings of the ATS,
April 1, 2005;
2(1):
50 - 60.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Barnes, I. M. Adcock, and K. Ito
Histone acetylation and deacetylation: importance in inflammatory lung diseases
Eur. Respir. J.,
March 1, 2005;
25(3):
552 - 563.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Barnes
Mediators of Chronic Obstructive Pulmonary Disease
Pharmacol. Rev.,
December 1, 2004;
56(4):
515 - 548.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Marwick, P. A. Kirkham, C. S. Stevenson, H. Danahay, J. Giddings, K. Butler, K. Donaldson, W. MacNee, and I. Rahman
Cigarette Smoke Alters Chromatin Remodeling and Induces Proinflammatory Genes in Rat Lungs
Am. J. Respir. Cell Mol. Biol.,
December 1, 2004;
31(6):
633 - 642.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Harju, R. Kaarteenaho-Wiik, R. Sirvio, P. Paakko, J.D. Crapo, T.D. Oury, Y. Soini, and V.L. Kinnula
Manganese superoxide dismutase is increased in the airways of smokers' lungs
Eur. Respir. J.,
November 1, 2004;
24(5):
765 - 771.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Li, R. Shu, G. Filippatos, and B. D. Uhal
Apoptosis in lung injury and remodeling
J Appl Physiol,
October 1, 2004;
97(4):
1535 - 1542.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. V. Usatyuk and V. Natarajan
Role of Mitogen-activated Protein Kinases in 4-Hydroxy-2-nonenal-induced Actin Remodeling and Barrier Function in Endothelial Cells
J. Biol. Chem.,
March 19, 2004;
279(12):
11789 - 11797.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. D. Wang, H. Tai, C. Xie, X. Wang, J. L. Wright, and A. Churg
Cigarette Smoke Produces Airway Wall Remodeling in Rat Tracheal Explants
Am. J. Respir. Crit. Care Med.,
November 15, 2003;
168(10):
1232 - 1236.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A.W. Boots, G.R.M.M. Haenen, and A. Bast
Oxidant metabolism in chronic obstructive pulmonary disease
Eur. Respir. J.,
November 2, 2003;
22(46_suppl):
14S - 27s.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P.J. Barnes, S.D. Shapiro, and R.A. Pauwels
Chronic obstructive pulmonary disease: molecular and cellularmechanisms
Eur. Respir. J.,
October 1, 2003;
22(4):
672 - 688.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. M. Tuder, L. Zhen, C. Y. Cho, L. Taraseviciene-Stewart, Y. Kasahara, D. Salvemini, N. F. Voelkel, and S. C. Flores
Oxidative Stress and Apoptosis Interact and Cause Emphysema Due to Vascular Endothelial Growth Factor Receptor Blockade
Am. J. Respir. Cell Mol. Biol.,
July 1, 2003;
29(1):
88 - 97.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. H. Risby
Further Discussion on Breath Condensate Analysis
Am. J. Respir. Crit. Care Med.,
May 15, 2003;
167(10):
1301 - 1302.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Corradi, I. Rubinstein, R. Andreoli, P. Manini, A. Caglieri, D. Poli, R. Alinovi, and A. Mutti
Aldehydes in Exhaled Breath Condensate of Patients with Chronic Obstructive Pulmonary Disease
Am. J. Respir. Crit. Care Med.,
May 15, 2003;
167(10):
1380 - 1386.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Tobin
Chronic Obstructive Pulmonary Disease, Pollution, Pulmonary Vascular Disease, Transplantation, Pleural Disease, and Lung Cancer in AJRCCM 2002
Am. J. Respir. Crit. Care Med.,
February 1, 2003;
167(3):
356 - 370.
[Full Text]
[PDF]
|
|
|
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