NADPH oxidase 4 deficiency reduces aquaporin-2 mRNA expression in cultured renal collecting duct principal cells via increased PDE3 and PDE4 activity

Article Article scientifique Article NADPH oxidase 4 deficiency reduces aquaporin-2 mRNA expression in cultured renal collecting duct principal cells via increased PDE3 and PDE4 activity eng 2014 author Feraille Eric 27356 author Bernabeu Dizin Eva 650786 author Monnay Isabelle 510200 author Derouette Jean-Paul 88087 author Szanto Eniko 583857 author Martin Pierre-Yves 65591 author De Seigneux Matthey Sophie 105798 author Hasler Udo 134082 e87239 10.1371/journal.pone.0087239 24466344 1932-6203 The final control of renal water reabsorption occurs in the collecting duct (CD) and relies on regulated expression of aquaporin-2 (AQP2) in principal CD cells. AQP2 transcription is primarily induced by type 2 vasopressin receptor (V2R)-cAMP-protein kinase A (PKA) signaling but also by other factors, including TonEBP and NF-κB. NAPDH oxidase 4 (NOX4) represents a major source of reactive oxygen species (ROS) in the kidney. Because NOX-derived ROS may alter PKA, TonEBP and NF-κB activity, we examined the effects of NOX4 depletion on AQP2 expression. Depleted NOX4 expression by siRNA (siNOX4) in mpkCCDcl4 cells attenuated increased AQP2 mRNA expression by arginine vasopressin (AVP) but not by hypertonicity, which induces both TonEBP and NF-κB activity. AVP-induced AQP2 expression was similarly decreased by the flavoprotein inhibitor diphenyleneiodonium. siNOX4 altered neither TonEBP nor NF-κB activity but attenuated AVP-inducible cellular cAMP concentration, PKA activity and CREB phosphorylation as well as AQP2 mRNA expression induced by forskolin, a potent activator of adenylate cyclase. The repressive effect of siNOX4 on AVP-induced AQP2 mRNA expression was abolished by the non-selective phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine (IBMX) and was significantly decreased by selective PDE antagonists cilostamide and rolipram, but not vinpocetine, which respectively target PDE3, PDE4 and PDE1. Thus, by inhibiting PDE3 and PDE4 activity NOX4-derived ROS may contribute to V2R-cAMP-PKA signaling and enhance AQP2 transcription. 1-Methyl-3-isobutylxanthine Animals Aquaporin 2/genetics/metabolism Arginine Vasopressin/metabolism Blotting, Western Cyclic AMP/metabolism Cyclic Nucleotide Phosphodiesterases, Type 3/metabolism Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism Kidney Tubules, Collecting/cytology Mice NADPH Oxidase/deficiency Quinolones RNA, Messenger/genetics/metabolism RNA, Small Interfering/genetics Reactive Oxygen Species/metabolism Real-Time Polymerase Chain Reaction Rolipram Signal Transduction/physiology Dewey 612 Dewey 616 134 Département de physiologie cellulaire et métabolisme 21C 56 Département de médecine 221 false 21 Groupe Pierre-Yves Martin (néphrologie) 30 897 Insuffisance rénale chronique 941 20 Laboratoire de physiologie et pathophysiologie des cellules rénales 29 465 Stress oxydatif et insuline 795 PloS one 9 1 0fc30fd0-a381-44ea-a092-11a010d8f2b9 Article (Published version) Public journal.pone.0087239 copie.pdf 767307 application/pdf CC BY openAccess Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme Faculté de médecine / Section de médecine clinique / Département de médecine

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NADPH oxidase 4 deficiency reduces aquaporin-2 mRNA expression in cultured renal collecting duct principal cells via increased PDE3 and PDE4 activity	PloS one			2014	579	324

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