title: The Potential Role of 8-Oxoguanine DNA Glycosylase-Driven DNA Base Excision Repair in Exercise-Induced Asthma.
abstract: Asthma is characterized by reversible airway narrowing, shortness of breath, wheezing, coughing, and other symptoms driven by chronic inflammatory processes, commonly triggered by allergens. In 90% of asthmatics, most of these symptoms can also be triggered by intense physical activities and severely exacerbated by environmental factors. This condition is known as exercise-induced asthma (EIA). Current theories explaining EIA pathogenesis involve osmotic and/or thermal alterations in the airways caused by changes in respiratory airflow during exercise. These changes, along with existing airway inflammatory conditions, are associated with increased cellular levels of reactive oxygen species (ROS) affecting important biomolecules including DNA, although the underlying molecular mechanisms have not been completely elucidated. One of the most abundant oxidative DNA lesions is 8-oxoguanine (8-oxoG), which is repaired by 8-oxoguanine DNA glycosylase 1 (OGG1) during the base excision repair (BER) pathway. Whole-genome expression analyses suggest a cellular response to OGG1-BER, involving genes that may have a role in the pathophysiology of EIA leading to mast cell degranulation, airway hyperresponsiveness, and bronchoconstriction. Accordingly, this review discusses a potential new hypothesis in which OGG1-BER-induced gene expression is associated with EIA symptoms.
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: KarryAnne K
authors.initials: KK
authors.lastname: Belanger
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA; Sealy Center for Molecular Medicine, School of Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA; Sealy Center for Environmental Health and Medicine, School of Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Bill T
authors.initials: BT
authors.lastname: Ameredes
authors.affiliation: Sealy Center for Molecular Medicine, School of Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA; Sealy Center for Environmental Health and Medicine, School of Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Istvan
authors.initials: I
authors.lastname: Boldogh
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Leopoldo
authors.identifier: 0000-0001-7964-7402
authors.initials: L
authors.lastname: Aguilera-Aguirre
mesh_terms: D000818:Animals; D001249:Asthma / Q000378:metabolism*; D016084:Bronchoconstriction; D004247:DNA / Q000032:analysis; D045647:DNA Glycosylases / Q000378:metabolism*; D004260:DNA Repair; D015444:Exercise; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D007249:Inflammation; D015227:Lipid Peroxidation; D008407:Mast Cells / Q000166:cytology; D051379:Mice; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D017382:Reactive Oxygen Species; C024829:8-hydroxyguanine; D006147:Guanine; D004247:DNA; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse