Cigarette smoke induces nucleic-acid oxidation in lung fibroblasts.

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.

[1]  R. Pierce,et al.  Oxidative damage to nucleic acids in severe emphysema. , 2009, Chest.

[2]  Shyam Biswal,et al.  Cigarette smoke-induced emphysema in A/J mice is associated with pulmonary oxidative stress, apoptosis of lung cells, and global alterations in gene expression. , 2009, American journal of physiology. Lung cellular and molecular physiology.

[3]  G. Wilson,et al.  Hypoxia-induced oxidative base modifications in the VEGF hypoxia-response element are associated with transcriptionally active nucleosomes. , 2009, Free radical biology & medicine.

[4]  M. O’Reilly,et al.  p21(Cip1) protects against oxidative stress by suppressing ER-dependent activation of mitochondrial death pathways. , 2009, Free radical biology & medicine.

[5]  J. Leader,et al.  Association of radiographic emphysema and airflow obstruction with lung cancer. , 2008, American journal of respiratory and critical care medicine.

[6]  T. Betsuyaku,et al.  Distal airways in mice exposed to cigarette smoke: Nrf2-regulated genes are increased in Clara cells. , 2008, American journal of respiratory cell and molecular biology.

[7]  Mei Wu,et al.  Enhanced sensitivity to DNA damage induced by cooking oil fumes in human OGG1 deficient cells , 2008, Environmental and molecular mutagenesis.

[8]  D. Zharkov.  Base excision DNA repair , 2008, Cellular and Molecular Life Sciences.

[9]  A. van Hoof,et al.  Messenger RNA regulation: to translate or to degrade , 2008, The EMBO journal.

[10]  Laimute Taraseviciene-Stewart,et al.  Molecular pathogenesis of emphysema. , 2008, The Journal of clinical investigation.

[11]  T. Betsuyaku,et al.  Bronchiolar chemokine expression is different after single versus repeated cigarette smoke exposure , 2008, Respiratory research.

[12]  G. Wilson,et al.  Sequence-specific oxidative base modifications in hypoxia-inducible genes. , 2007, Free radical biology & medicine.

[13]  M. Smith,et al.  Oxidative RNA damage and neurodegeneration. , 2007, Current medicinal chemistry.

[14]  I. Boldogh,et al.  Increased ROS generation in subsets of OGG1 knockout fibroblast cells , 2007, Mechanisms of Ageing and Development.

[15]  Samuel H. Wilson,et al.  Stimulation of NEIL2-mediated Oxidized Base Excision Repair via YB-1 Interaction during Oxidative Stress* , 2007, Journal of Biological Chemistry.

[16]  X. Shan,et al.  The FASEB Journal • Research Communication Messenger RNA oxidation is an early event preceding cell death and causes reduced protein expression , 2022 .

[17]  E. Stadtman,et al.  Oxidized messenger RNA induces translation errors , 2007, Proceedings of the National Academy of Sciences.

[18]  A. Churg,et al.  Current Concepts in Mechanisms of Emphysema , 2007, Toxicologic pathology.

[19]  G. Wilson,et al.  Bending and breaking the code: dynamic changes in promoter integrity may underlie a new mechanism regulating gene expression. , 2007, American journal of physiology. Lung cellular and molecular physiology.

[20]  Dmitriy A Yablonskiy,et al.  Hyperpolarized 3He diffusion MRI and histology in pulmonary emphysema , 2006, Magnetic resonance in medicine.

[21]  S. Biswal,et al.  Role of lung maintenance program in the heterogeneity of lung destruction in emphysema. , 2006, Proceedings of the American Thoracic Society.

[22]  Zhongwei Li,et al.  RNA damage and surveillance under oxidative stress , 2006, IUBMB life.

[23]  W. Arap,et al.  State of the art. Cellular and molecular mechanisms of alveolar destruction in emphysema: an evolutionary perspective. , 2006, Proceedings of the American Thoracic Society.

[24]  L. Fabbri,et al.  Clusterin decreases oxidative stress in lung fibroblasts exposed to cigarette smoke. , 2006, American journal of respiratory and critical care medicine.

[25]  I. Adcock,et al.  Oxidative stress and redox regulation of lung inflammation in COPD , 2006, European Respiratory Journal.

[26]  M. Sekiguchi,et al.  Human polynucleotide phosphorylase protein in response to oxidative stress. , 2006, Biochemistry.

[27]  I. Rahman,et al.  Oxidant and antioxidant balance in the airways and airway diseases. , 2006, European journal of pharmacology.

[28]  A. M. Houghton,et al.  Elastin fragments drive disease progression in a murine model of emphysema. , 2006, The Journal of clinical investigation.

[29]  B. Van Houten,et al.  Role of mitochondrial DNA in toxic responses to oxidative stress. , 2006, DNA repair.

[30]  W. MacNee,et al.  Oxidants and COPD. , 2005, Current drug targets. Inflammation and allergy.

[31]  T. Ley,et al.  YB-1 Is Important for Late-Stage Embryonic Development, Optimal Cellular Stress Responses, and the Prevention of Premature Senescence , 2005, Molecular and Cellular Biology.

[32]  J. Ravanat,et al.  Hydrogen peroxide causes greater oxidation in cellular RNA than in DNA , 2005, Biological chemistry.

[33]  S. Rennard,et al.  Reversible cigarette smoke extract-induced DNA damage in human lung fibroblasts. , 2004, American journal of respiratory cell and molecular biology.

[34]  Irina Petrache,et al.  Genetic ablation of Nrf2 enhances susceptibility to cigarette smoke-induced emphysema in mice. , 2004, The Journal of clinical investigation.

[35]  M. Evans,et al.  Oxidative DNA damage and disease: induction, repair and significance. , 2004, Mutation research.

[36]  M. Cooke,et al.  Factors contributing to the outcome of oxidative damage to nucleic acids , 2004, BioEssays : news and reviews in molecular, cellular and developmental biology.

[37]  C. Witt,et al.  Nuclear YB‐1 expression as a negative prognostic marker in nonsmall cell lung cancer , 2004, European Respiratory Journal.

[38]  H. Izumi,et al.  The pleiotropic functions of the Y-box-binding protein, YB-1. , 2003, BioEssays : news and reviews in molecular, cellular and developmental biology.

[39]  M. Evans,et al.  Oxidative DNA damage: mechanisms, mutation, and disease , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[40]  B. Longoni,et al.  Cigarette smoke extract induces oxidative stress and apoptosis in human lung fibroblasts. , 2003, American journal of physiology. Lung cellular and molecular physiology.

[41]  T. Tsuzuki,et al.  Ogg1 knockout-associated lung tumorigenesis and its suppression by Mth1 gene disruption. , 2003, Cancer research.

[42]  Magnar Bjørås,et al.  Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA , 2003, Nature.

[43]  K. Aoshiba,et al.  Immunohistochemical Evaluation of Oxidative Stress in Murine Lungs After Cigarette Smoke Exposure , 2003, Inhalation toxicology.

[44]  A. Nunomura,et al.  Neuronal RNA oxidation is a prominent feature of dementia with Lewy bodies , 2002, Neuroreport.

[45]  M. Sekiguchi,et al.  Binding capacity of human YB-1 protein for RNA containing 8-oxoguanine. , 2002, Biochemistry.

[46]  B. Fischer,et al.  Neutrophil elastase induces MUC5AC gene expression in airway epithelium via a pathway involving reactive oxygen species. , 2002, American journal of respiratory cell and molecular biology.

[47]  T. Mio,et al.  Cytotoxic effects of cigarette smoke extract on an alveolar type II cell-derived cell line. , 2001, American journal of physiology. Lung cellular and molecular physiology.

[48]  R. Pauwels,et al.  Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. , 2001, American journal of respiratory and critical care medicine.

[49]  J. Radicella,et al.  The human OGG1 gene: structure, functions, and its implication in the process of carcinogenesis. , 2000, Archives of biochemistry and biophysics.

[50]  S. Shapiro,et al.  Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. , 1997, Science.

[51]  C. Betsholtz,et al.  PDGF-A Signaling Is a Critical Event in Lung Alveolar Myofibroblast Development and Alveogenesis , 1996, Cell.