Urothelial cells produce hydrogen peroxide through the activation of Duox1

• Published in: Free radical biology & medicine Vol. 49; no. 12; pp. 2040 - 2048
• Main Authors: Donkó, Ágnes, Ruisanchez, Éva, Orient, Anna, Enyedi, Balázs, Kapui, Réka, Péterfi, Zalán, de Deken, Xavier, Benyó, Zoltán, Geiszt, Miklós
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15-12-2010
• Subjects: Animals; Calcium Signaling - drug effects; Dual Oxidases; Duox; Enzyme Activation; Epithelial Cells - enzymology; Epithelial Cells - metabolism; Escherichia coli - growth & development; Hydrogen Peroxide - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Microbial Viability; NADPH oxidase; NADPH Oxidases - genetics; NADPH Oxidases - metabolism; OmniBank; Reactive oxygen species; Thapsigargin - pharmacology; TRPV Cation Channels - metabolism; TRPV4; Urinary Bladder - cytology; Urinary Bladder - microbiology; Urinary Bladder - physiology; Urothelium; Urothelium - cytology; Urothelium - physiology; Duox1; RHD2; Reactive oxygen species; OmniBank; Nox; TRPV4; NADPH oxidase; ROS; HRP; LPO; Duox; Urothelium
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2010.09.027

Hydrogen peroxide (H
2O
2) has important messenger and effector functions in the plant and animal kingdom. Phagocytes produce H
2O
2 to kill pathogens, and epithelial cells of large airways have also been reported to produce H
2O
2 for signaling and host defense purposes. In this report, we show for the first time that urothelial cells produce H
2O
2 in response to a calcium signal. Using a gene-deficient mouse model we also demonstrate that H
2O
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
2O
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
2O
2 production similar to that observed in plants.