| Cigarette smoke induces nucleic-acid oxidation in lung fibroblasts. | |
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MedLine Citation:
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PMID: 20008282 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Oxidative stress is widely proposed as a pathogenic mechanism for chronic obstructive pulmonary disease (COPD), but the molecular pathway connecting oxidative damage to tissue destruction remains to be fully defined. We suggest that reactive oxygen species (ROS) oxidatively damage nucleic acids, and this effect requires multiple repair mechanisms, particularly base excision pathway components 8-oxoguanine-DNA glycosylase (OGG1), endonuclease III homologue 1 (NTH1), and single-strand-selective monofunctional uracil-DNA glycosylase 1 (SMUG1), as well as the nucleic acid-binding protein, Y-box binding protein 1 (YB1). This study was therefore designed to define the levels of nucleic-acid oxidation and expression of genes involved in the repair of COPD and in corresponding models of this disease. We found significant oxidation of nucleic acids localized to alveolar lung fibroblasts, increased levels of OGG1 mRNA expression, and decreased concentrations of NTH1, SMUG1, and YB1 mRNA in lung samples from subjects with very severe COPD compared with little or no COPD. Mice exposed to cigarette smoke exhibited a time-dependent accumulation of nucleic-acid oxidation in alveolar fibroblasts, which was associated with an increase in OGG1 and YB1 mRNA concentrations. Similarly, human lung fibroblasts exposed to cigarette smoke extract exhibited ROS-dependent nucleic-acid oxidation. The short interfering RNA (siRNA)-dependent knockdown of OGG1 and YB1 expression increased nucleic-acid oxidation at the basal state and after exposure to cigarette smoke. Together, our results demonstrate ROS-dependent, cigarette smoke-induced nucleic-acid oxidation in alveolar fibroblasts, which may play a role in the pathogenesis of emphysema. |
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Authors:
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Gaetan Deslee; Tracy L Adair-Kirk; Tomoko Betsuyaku; Jason C Woods; Carla H Moore; David S Gierada; Susan H Conradi; Jeffrey J Atkinson; Holly M Toennies; John T Battaile; Dale K Kobayashi; G Alexander Patterson; 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: 2009-12-11 |
Journal Detail:
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Title: American journal of respiratory cell and molecular biology Volume: 43 ISSN: 1535-4989 ISO Abbreviation: Am. J. Respir. Cell Mol. Biol. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-25 Completed Date: 2010-11-10 Revised Date: 2011-11-01 |
Medline Journal Info:
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Nlm Unique ID: 8917225 Medline TA: Am J Respir Cell Mol Biol Country: United States |
Other Details:
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Languages: eng Pagination: 576-84 Citation Subset: IM |
Affiliation:
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Division of Pulmonary and Critical Care Medicine, School of Medicine, Washington University, St. Louis, Missouri 63110, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Animals Apoptosis DNA Glycosylases / antagonists & inhibitors, genetics, metabolism DNA-Binding Proteins / antagonists & inhibitors, genetics, metabolism Deoxyribonuclease (Pyrimidine Dimer) / metabolism Down-Regulation Emphysema / enzymology, genetics, pathology Female Fibroblasts / enzymology, metabolism*, pathology* Humans Lung Male Mice Mice, Inbred C57BL Middle Aged Nuclear Proteins / antagonists & inhibitors, genetics, metabolism Nucleic Acids / metabolism* Oxidation-Reduction Pulmonary Alveoli / enzymology, pathology RNA, Messenger / genetics, metabolism Reactive Oxygen Species / metabolism Smoking / adverse effects* Uracil-DNA Glycosidase / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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P50HL084922/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA-Binding Proteins; 0/Nuclear Proteins; 0/Nucleic Acids; 0/RNA, Messenger; 0/Reactive Oxygen Species; 0/YBX1 protein, human; EC 3.1.25.1/Deoxyribonuclease (Pyrimidine Dimer); EC 3.1.25.1/NTHL1 protein, human; EC 3.2.2.-/DNA Glycosylases; EC 3.2.2.-/SMUG1 protein, human; EC 3.2.2.-/Uracil-DNA Glycosidase; EC 3.2.2.-/oxoguanine glycosylase 1, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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