Oxidative damage to nucleic acids in severe emphysema

Gaetan Deslee, Jason C. Woods, Carla Moore, Susan H. Conradi, David S. Gierada, Jeffrey J. Atkinson, John T. Battaile, Lucy Liu, G. Alexander Patterson, Tracy L. Adair-Kirk, Michael J. Holtzman, Richard A. Pierce

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Background: Oxidative stress is a key element in the pathogenesis of emphysema, but oxidation of nucleic acids has been largely overlooked. The aim of this study was to investigate oxidative damage to nucleic acids in severe emphysematous lungs. Methods: Thirteen human severe emphysematous lungs, including five with α 1-antitrypsin deficiency (AATD), were obtained from patients receiving lung transplantation. Control lung tissue was obtained from non-COPD lungs (n = 8) and donor lungs (n = 8). DNA and RNA oxidation were investigated by immunochemistry. Morphometry (mean linear intercept [Lm] and CT scan) and immunostaining for CD68 and neutrophil elastase also were performed. Results: Nucleic acid oxidation was increased in alveolar wall cells in emphysematous lungs compared to non-COPD and donor lungs (p < 0.01). In emphysematous lungs, oxidative damage to nucleic acids in alveolar wall cells was increased in the more severe emphysematous areas assessed by histology (Lm, > 0.5 mm; p < 0.05) and CT scan (< -950 Hounsfield units; p < 0.05). Compared to classic emphysema, AATD lungs exhibited higher levels of nucleic acid oxidation in macrophages (p < 0.05) and airway epithelial cells (p < 0.01). Pretreatments with DNase and RNase demonstrated that RNA oxidation was more prevalent than DNA oxidation in alveolar wall cells. Conclusions: We demonstrated for the first time that nucleic acids, especially RNA, are oxidized in human emphysematous lungs. The correlation between the levels of oxidative damage to nucleic acids in alveolar wall cells and the severity of emphysema suggest a potential role in the pathogenesis of emphysema.

Original languageEnglish (US)
Pages (from-to)965-974
Number of pages10
JournalChest
Volume135
Issue number4
DOIs
StatePublished - Apr 1 2009

Fingerprint

Emphysema
Nucleic Acids
Lung
Alveolar Epithelial Cells
RNA
Tissue Donors
Immunochemistry
Leukocyte Elastase
Deoxyribonucleases
Lung Transplantation
DNA
Ribonucleases
Oxidative Stress
Epithelial Cells
Macrophages

Keywords

  • α -antitrypsin deficiency
  • Emphysema
  • Nucleic acids
  • Oxidative stress
  • RNA

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Deslee, G., Woods, J. C., Moore, C., Conradi, S. H., Gierada, D. S., Atkinson, J. J., ... Pierce, R. A. (2009). Oxidative damage to nucleic acids in severe emphysema. Chest, 135(4), 965-974. https://doi.org/10.1378/chest.08-2257

Oxidative damage to nucleic acids in severe emphysema. / Deslee, Gaetan; Woods, Jason C.; Moore, Carla; Conradi, Susan H.; Gierada, David S.; Atkinson, Jeffrey J.; Battaile, John T.; Liu, Lucy; Alexander Patterson, G.; Adair-Kirk, Tracy L.; Holtzman, Michael J.; Pierce, Richard A.

In: Chest, Vol. 135, No. 4, 01.04.2009, p. 965-974.

Research output: Contribution to journalArticle

Deslee, G, Woods, JC, Moore, C, Conradi, SH, Gierada, DS, Atkinson, JJ, Battaile, JT, Liu, L, Alexander Patterson, G, Adair-Kirk, TL, Holtzman, MJ & Pierce, RA 2009, 'Oxidative damage to nucleic acids in severe emphysema', Chest, vol. 135, no. 4, pp. 965-974. https://doi.org/10.1378/chest.08-2257
Deslee G, Woods JC, Moore C, Conradi SH, Gierada DS, Atkinson JJ et al. Oxidative damage to nucleic acids in severe emphysema. Chest. 2009 Apr 1;135(4):965-974. https://doi.org/10.1378/chest.08-2257
Deslee, Gaetan ; Woods, Jason C. ; Moore, Carla ; Conradi, Susan H. ; Gierada, David S. ; Atkinson, Jeffrey J. ; Battaile, John T. ; Liu, Lucy ; Alexander Patterson, G. ; Adair-Kirk, Tracy L. ; Holtzman, Michael J. ; Pierce, Richard A. / Oxidative damage to nucleic acids in severe emphysema. In: Chest. 2009 ; Vol. 135, No. 4. pp. 965-974.
@article{efaa2de9abcb4b79b4ccfea50c09ac26,
title = "Oxidative damage to nucleic acids in severe emphysema",
abstract = "Background: Oxidative stress is a key element in the pathogenesis of emphysema, but oxidation of nucleic acids has been largely overlooked. The aim of this study was to investigate oxidative damage to nucleic acids in severe emphysematous lungs. Methods: Thirteen human severe emphysematous lungs, including five with α 1-antitrypsin deficiency (AATD), were obtained from patients receiving lung transplantation. Control lung tissue was obtained from non-COPD lungs (n = 8) and donor lungs (n = 8). DNA and RNA oxidation were investigated by immunochemistry. Morphometry (mean linear intercept [Lm] and CT scan) and immunostaining for CD68 and neutrophil elastase also were performed. Results: Nucleic acid oxidation was increased in alveolar wall cells in emphysematous lungs compared to non-COPD and donor lungs (p < 0.01). In emphysematous lungs, oxidative damage to nucleic acids in alveolar wall cells was increased in the more severe emphysematous areas assessed by histology (Lm, > 0.5 mm; p < 0.05) and CT scan (< -950 Hounsfield units; p < 0.05). Compared to classic emphysema, AATD lungs exhibited higher levels of nucleic acid oxidation in macrophages (p < 0.05) and airway epithelial cells (p < 0.01). Pretreatments with DNase and RNase demonstrated that RNA oxidation was more prevalent than DNA oxidation in alveolar wall cells. Conclusions: We demonstrated for the first time that nucleic acids, especially RNA, are oxidized in human emphysematous lungs. The correlation between the levels of oxidative damage to nucleic acids in alveolar wall cells and the severity of emphysema suggest a potential role in the pathogenesis of emphysema.",
keywords = "α -antitrypsin deficiency, Emphysema, Nucleic acids, Oxidative stress, RNA",
author = "Gaetan Deslee and Woods, {Jason C.} and Carla Moore and Conradi, {Susan H.} and Gierada, {David S.} and Atkinson, {Jeffrey J.} and Battaile, {John T.} and Lucy Liu and {Alexander Patterson}, G. and Adair-Kirk, {Tracy L.} and Holtzman, {Michael J.} and Pierce, {Richard A.}",
year = "2009",
month = "4",
day = "1",
doi = "10.1378/chest.08-2257",
language = "English (US)",
volume = "135",
pages = "965--974",
journal = "Chest",
issn = "0012-3692",
publisher = "American College of Chest Physicians",
number = "4",

}

TY - JOUR

T1 - Oxidative damage to nucleic acids in severe emphysema

AU - Deslee, Gaetan

AU - Woods, Jason C.

AU - Moore, Carla

AU - Conradi, Susan H.

AU - Gierada, David S.

AU - Atkinson, Jeffrey J.

AU - Battaile, John T.

AU - Liu, Lucy

AU - Alexander Patterson, G.

AU - Adair-Kirk, Tracy L.

AU - Holtzman, Michael J.

AU - Pierce, Richard A.

PY - 2009/4/1

Y1 - 2009/4/1

N2 - Background: Oxidative stress is a key element in the pathogenesis of emphysema, but oxidation of nucleic acids has been largely overlooked. The aim of this study was to investigate oxidative damage to nucleic acids in severe emphysematous lungs. Methods: Thirteen human severe emphysematous lungs, including five with α 1-antitrypsin deficiency (AATD), were obtained from patients receiving lung transplantation. Control lung tissue was obtained from non-COPD lungs (n = 8) and donor lungs (n = 8). DNA and RNA oxidation were investigated by immunochemistry. Morphometry (mean linear intercept [Lm] and CT scan) and immunostaining for CD68 and neutrophil elastase also were performed. Results: Nucleic acid oxidation was increased in alveolar wall cells in emphysematous lungs compared to non-COPD and donor lungs (p < 0.01). In emphysematous lungs, oxidative damage to nucleic acids in alveolar wall cells was increased in the more severe emphysematous areas assessed by histology (Lm, > 0.5 mm; p < 0.05) and CT scan (< -950 Hounsfield units; p < 0.05). Compared to classic emphysema, AATD lungs exhibited higher levels of nucleic acid oxidation in macrophages (p < 0.05) and airway epithelial cells (p < 0.01). Pretreatments with DNase and RNase demonstrated that RNA oxidation was more prevalent than DNA oxidation in alveolar wall cells. Conclusions: We demonstrated for the first time that nucleic acids, especially RNA, are oxidized in human emphysematous lungs. The correlation between the levels of oxidative damage to nucleic acids in alveolar wall cells and the severity of emphysema suggest a potential role in the pathogenesis of emphysema.

AB - Background: Oxidative stress is a key element in the pathogenesis of emphysema, but oxidation of nucleic acids has been largely overlooked. The aim of this study was to investigate oxidative damage to nucleic acids in severe emphysematous lungs. Methods: Thirteen human severe emphysematous lungs, including five with α 1-antitrypsin deficiency (AATD), were obtained from patients receiving lung transplantation. Control lung tissue was obtained from non-COPD lungs (n = 8) and donor lungs (n = 8). DNA and RNA oxidation were investigated by immunochemistry. Morphometry (mean linear intercept [Lm] and CT scan) and immunostaining for CD68 and neutrophil elastase also were performed. Results: Nucleic acid oxidation was increased in alveolar wall cells in emphysematous lungs compared to non-COPD and donor lungs (p < 0.01). In emphysematous lungs, oxidative damage to nucleic acids in alveolar wall cells was increased in the more severe emphysematous areas assessed by histology (Lm, > 0.5 mm; p < 0.05) and CT scan (< -950 Hounsfield units; p < 0.05). Compared to classic emphysema, AATD lungs exhibited higher levels of nucleic acid oxidation in macrophages (p < 0.05) and airway epithelial cells (p < 0.01). Pretreatments with DNase and RNase demonstrated that RNA oxidation was more prevalent than DNA oxidation in alveolar wall cells. Conclusions: We demonstrated for the first time that nucleic acids, especially RNA, are oxidized in human emphysematous lungs. The correlation between the levels of oxidative damage to nucleic acids in alveolar wall cells and the severity of emphysema suggest a potential role in the pathogenesis of emphysema.

KW - α -antitrypsin deficiency

KW - Emphysema

KW - Nucleic acids

KW - Oxidative stress

KW - RNA

UR - http://www.scopus.com/inward/record.url?scp=64749097430&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=64749097430&partnerID=8YFLogxK

U2 - 10.1378/chest.08-2257

DO - 10.1378/chest.08-2257

M3 - Article

VL - 135

SP - 965

EP - 974

JO - Chest

JF - Chest

SN - 0012-3692

IS - 4

ER -