| Oxidative damage to nucleic acids in severe emphysema. | |
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MedLine Citation:
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PMID: 19118262 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 alpha(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. |
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Authors:
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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 |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-12-31 |
Journal Detail:
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Title: Chest Volume: 135 ISSN: 1931-3543 ISO Abbreviation: Chest Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-04-07 Completed Date: 2009-04-20 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0231335 Medline TA: Chest Country: United States |
Other Details:
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Languages: eng Pagination: 965-74 Citation Subset: AIM; IM |
Affiliation:
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Washington University School of Medicine, Division of Pulmonary and Critical Care Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Antigens, CD / analysis Antigens, Differentiation, Myelomonocytic / analysis DNA / metabolism Female Humans Immunochemistry Leukocyte Elastase / analysis Lung / metabolism Male Middle Aged Nucleic Acids / metabolism* Oxidation-Reduction Oxidative Stress / physiology* Pulmonary Alveoli / cytology Pulmonary Emphysema / metabolism* RNA / metabolism alpha 1-Antitrypsin Deficiency / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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P50 HL 084922/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/Antigens, Differentiation, Myelomonocytic; 0/CD68 antigen, human; 0/Nucleic Acids; 63231-63-0/RNA; 9007-49-2/DNA; EC 3.4.21.37/Leukocyte Elastase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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