Pathophysiology of bronchoconstriction: Role of oxidatively damaged DNA repair

Attila Bacsi, Lang Pan, Xueqing Ba, Istvan Boldogh

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Purpose of review To provide an overview on the present understanding of roles of oxidative DNA damage repair in cell signaling underlying bronchoconstriction common to, but not restricted to various forms of asthma and chronic obstructive pulmonary disease. Recent findings Bronchoconstriction is a tightening of smooth muscle surrounding the bronchi and bronchioles with consequent wheezing and shortness of breath. Key stimuli include air pollutants, viral infections, allergens, thermal and osmotic changes, and shear stress of mucosal epithelium, triggering a wide range of cellular, vascular, and neural events. Although activation of nerve fibers, the role of G-proteins, protein kinases and Ca, and molecular interaction within contracting filaments of muscle are well defined, the overarching mechanisms by which a wide range of stimuli initiate these events are not fully understood. Many, if not all, stimuli increase levels of reactive oxygen species, which are signaling and oxidatively modifying macromolecules, including DNA. The primary reactive oxygen species target in DNA is guanine, and 8- oxoguanine is one of the most abundant base lesions. It is repaired by 8-oxoguanine DNA glycosylase1 during base excision repair processes. The product, free 8-oxo-7,8-dihydro-20-deoxyguanosine base, is bound by 8-oxoguanine DNA glycosylase1 with high affinity, and the complex then functions as an activator of small guanosine triphosphatases, triggering pathways for inducing gene expression and contraction of intracellular filaments in mast and smooth muscle cells. Summary Oxidative DNA damage repair-mediated cell activation signaling result in gene expression that 'primes' the mucosal epithelium and submucosal tissues to generate mediators of airway smooth muscle contractions.

Original languageEnglish (US)
Pages (from-to)59-67
Number of pages9
JournalCurrent Opinion in Allergy and Clinical Immunology
Volume16
Issue number1
DOIs
StatePublished - 2016

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Keywords

  • 8-oxoguanine DNA glycosylase1
  • Muscle constriction
  • Oxidative DNA damage
  • Small gtpases

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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