title: Duox2 exhibits potent heme peroxidase activity in human respiratory tract epithelium.
abstract: The dual oxidase isozymes Duox1 and Duox2 exhibit functional NADPH:O(2) oxidoreductase activity in thyroid and respiratory tract cells and are thought to be essential for H(2)O(2) generation in these tissues. However, it is not universally accepted that the heme peroxidase domains of the Duox isozymes are functional. To address this question, we modulated Duox2 expression in human tracheobronchial epithelial (TBE) cell culture systems and quantified peroxidase activity. We discovered that interferon-gamma (IFN-gamma) induced robust peroxidase activity in TBE cells that paralleled Duox2 expression. IFN-gamma-induced peroxidase activity was abolished in the presence of sodium azide, which implicated the activation of a heme peroxidase. IFN-gamma-induced peroxidase activity was abolished in TBE cell lines expressing anti-Duox2 short hairpin RNA transcripts. Together, these data unequivocally demonstrated that Duox2 contains a functional heme peroxidase in intact respiratory tract epithelium.
authors.affiliation: Department of Internal Medicine, Division of Pulmonary/Critical Care Medicine, School of Medicine, University of California, 451 East Health Sciences Road, Room 6521, Davis, 95616, USA. rwharper@ucdavis.edu
authors.forename: Richart W
authors.initials: RW
authors.lastname: Harper
authors.forename: Changhong
authors.initials: C
authors.lastname: Xu
authors.forename: Michael
authors.initials: M
authors.lastname: McManus
authors.forename: Amy
authors.initials: A
authors.lastname: Heidersbach
authors.forename: Jason P
authors.initials: JP
authors.lastname: Eiserich
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002461:Cell Line, Transformed; D000074623:Dual Oxidases; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D005420:Flavoproteins / Q000096:biosynthesis* / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D019255:NADPH Oxidases / Q000096:biosynthesis* / Q000235:genetics; D009928:Organ Specificity; D010544:Peroxidases / Q000096:biosynthesis* / Q000235:genetics; D016372:RNA, Antisense / Q000096:biosynthesis / Q000235:genetics; D020545:Respiratory Mucosa / Q000201:enzymology*; D013961:Thyroid Gland / Q000201:enzymology
chemical_list: D000970:Antineoplastic Agents; D005420:Flavoproteins; D016372:RNA, Antisense; D007371:Interferon-gamma; D000074623:Dual Oxidases; D010544:Peroxidases; D019255:NADPH Oxidases; C431515:DUOX2 protein, human