title: Oxidative stress and chromatin remodeling in chronic obstructive pulmonary disease and smoking-related diseases.
abstract: CONCLUSIONS
  Chronic obstructive pulmonary disease (COPD) is predominantly a tobacco smoke-triggered disease with features of chronic low-grade systemic inflammation and aging (inflammaging) of the lung associated with steroid resistance induced by cigarette smoke (CS)-mediated oxidative stress. Oxidative stress induces various kinase signaling pathways leading to chromatin modifications (histone acetylation/deacetylation and histone methylation/demethylation) in inflammation, senescence, and steroid resistance.
  
  
  BACKGROUND
  Histone mono-, di-, or tri-methylation at lysine residues result in either gene activation (H3K4, H3K36, and H3K79) or repression (H3K9, H3K27, and H3K20). Cross-talk occurs between various epigenetic marks on histones and DNA methylation. Both CS and oxidants alter histone acetylation/deacetylation and methylation/demethylation leading to enhanced proinflammatory gene expression. Chromatin modifications occur in lungs of patients with COPD. Histone deacetylase 2 (HDAC2) reduction (levels and activity) is associated with steroid resistance in response to oxidative stress.
  
  
  RESULTS
  Histone modifications are associated with DNA damage/repair and epigenomic instability as well as premature lung aging, which have implications in the pathogenesis of COPD. HDAC2/SIRTUIN1 (SIRT1)-dependent chromatin modifications are associated with DNA damage-induced inflammation and senescence in response to CS-mediated oxidative stress.
  
  
  CONCLUSIONS
  Understanding CS/oxidative stress-mediated chromatin modifications and the cross-talk between histone acetylation and methylation will demonstrate the involvement of epigenetic regulation of chromatin remodeling in inflammaging. This will lead to identification of novel epigenetic-based therapies against COPD and other smoking-related lung diseases. Pharmacological activation of HDAC2/SIRT1 or reversal of their oxidative post-translational modifications may offer therapies for treatment of COPD and CS-related diseases based on epigenetic histone modifications.
authors.affiliation: Department of Environmental Medicine, Lung Biology and Disease Program, University of Rochester Medical Center, Rochester, New York 14642, USA.
authors.forename: Isaac K
authors.initials: IK
authors.lastname: Sundar
authors.forename: Hongwei
authors.initials: H
authors.lastname: Yao
authors.forename: Irfan
authors.initials: I
authors.lastname: Rahman
mesh_terms: D000107:Acetylation; D042002:Chromatin Assembly and Disassembly; D019175:DNA Methylation; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010770:Phosphotransferases / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology*; D015398:Signal Transduction; D012907:Smoking
chemical_list: D006657:Histones; D010770:Phosphotransferases