title: Urothelial cells produce hydrogen peroxide through the activation of Duox1.
abstract: Hydrogen peroxide (H(2)O(2)) has important messenger and effector functions in the plant and animal kingdom. Phagocytes produce H(2)O(2) to kill pathogens, and epithelial cells of large airways have also been reported to produce H(2)O(2) for signaling and host defense purposes. In this report, we show for the first time that urothelial cells produce H(2)O(2) in response to a calcium signal. Using a gene-deficient mouse model we also demonstrate that H(2)O(2) is produced by the NADPH oxidase Duox1, which is expressed in the mouse urothelium. In contrast, we found no evidence for the expression of lactoperoxidase, an enzyme that has been shown to cooperate with Duox enzymes. We also found that specific activation of TRPV4 calcium channels elicits a calcium signal and stimulates H(2)O(2) production in urothelial cells. Furthermore, we detected altered pressure responses in the urinary bladders of Duox1 knockout animals. Our results raise the possibility that mechanosensing in epithelial cells involves calcium-dependent H(2)O(2) production similar to that observed in plants.
authors.affiliation: Department of Physiology, Semmelweis University, Budapest, Hungary.
authors.forename: Agnes
authors.initials: A
authors.lastname: Donkó
authors.forename: Eva
authors.initials: E
authors.lastname: Ruisanchez
authors.forename: Anna
authors.initials: A
authors.lastname: Orient
authors.forename: Balázs
authors.initials: B
authors.lastname: Enyedi
authors.forename: Réka
authors.initials: R
authors.lastname: Kapui
authors.forename: Zalán
authors.initials: Z
authors.lastname: Péterfi
authors.forename: Xavier
authors.initials: X
authors.lastname: de Deken
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Benyó
authors.forename: Miklós
authors.initials: M
authors.lastname: Geiszt
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D000074623:Dual Oxidases; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000201:enzymology* / Q000378:metabolism; D004926:Escherichia coli / Q000254:growth & development; D006861:Hydrogen Peroxide / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050296:Microbial Viability; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D001743:Urinary Bladder / Q000166:cytology* / Q000382:microbiology / Q000502:physiology; D019459:Urothelium / Q000166:cytology / Q000502:physiology
chemical_list: D050916:TRPV Cation Channels; C486576:Trpv4 protein, mouse; D019284:Thapsigargin; D006861:Hydrogen Peroxide; D000074623:Dual Oxidases; D019255:NADPH Oxidases; C519130:Duox1 protein, mouse