Cigarette smoke induces nucleic-acid oxidation in lung fibroblasts

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

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)576-584
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume43
Issue number5
DOIs
Publication statusPublished - 2010 Nov 1
Externally publishedYes

Fingerprint

Fibroblasts
Smoke
Tobacco Products
Nucleic Acids
Y-Box-Binding Protein 1
Oxidation
Lung
Pulmonary diseases
Chronic Obstructive Pulmonary Disease
Uracil-DNA Glycosidase
Reactive Oxygen Species
Messenger RNA
Repair
DNA Glycosylases
Oxidative stress
Endonucleases
Emphysema
Small Interfering RNA
Carrier Proteins
Oxidative Stress

Keywords

  • COPD
  • DNA/RNA repair
  • Emphysema
  • Nucleic-acid oxidation

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Deslee, G., Adair-Kirk, T. L., Betsuyaku, T., Woods, J. C., Moore, C. H., Gierada, D. S., ... Pierce, R. A. (2010). Cigarette smoke induces nucleic-acid oxidation in lung fibroblasts. American Journal of Respiratory Cell and Molecular Biology, 43(5), 576-584. https://doi.org/10.1165/rcmb.2009-0221OC

Cigarette smoke induces nucleic-acid oxidation in lung fibroblasts. / Deslee, Gaetan; Adair-Kirk, Tracy L.; Betsuyaku, Tomoko; Woods, Jason C.; Moore, Carla H.; Gierada, David S.; Conradi, Susan H.; Atkinson, Jeffrey J.; Toennies, Holly M.; Battaile, John T.; Kobayashi, Dale K.; Patterson, G. Alexander; Holtzman, Michael J.; Pierce, Richard A.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 43, No. 5, 01.11.2010, p. 576-584.

Research output: Contribution to journalArticle

Deslee, G, Adair-Kirk, TL, Betsuyaku, T, Woods, JC, Moore, CH, Gierada, DS, Conradi, SH, Atkinson, JJ, Toennies, HM, Battaile, JT, Kobayashi, DK, Patterson, GA, Holtzman, MJ & Pierce, RA 2010, 'Cigarette smoke induces nucleic-acid oxidation in lung fibroblasts', American Journal of Respiratory Cell and Molecular Biology, vol. 43, no. 5, pp. 576-584. https://doi.org/10.1165/rcmb.2009-0221OC
Deslee, Gaetan ; Adair-Kirk, Tracy L. ; Betsuyaku, Tomoko ; Woods, Jason C. ; Moore, Carla H. ; Gierada, David S. ; Conradi, Susan H. ; Atkinson, Jeffrey J. ; Toennies, Holly M. ; Battaile, John T. ; Kobayashi, Dale K. ; Patterson, G. Alexander ; Holtzman, Michael J. ; Pierce, Richard A. / Cigarette smoke induces nucleic-acid oxidation in lung fibroblasts. In: American Journal of Respiratory Cell and Molecular Biology. 2010 ; Vol. 43, No. 5. pp. 576-584.
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