title: Dual oxidase2 is expressed all along the digestive tract.
abstract: The dual oxidase (Duox)2 flavoprotein is strongly expressed in the thyroid gland, where it plays a critical role in the synthesis of thyroid hormones by providing thyroperoxidase with H2O2. DUOX2 mRNA was recently detected by RT-PCR and in-situ hybridization experiments in other tissues, such as rat colon and rat and human epithelial cells from the salivary excretory ducts and rectal glands. We examined Duox2 expression at the protein level throughout the porcine digestive tract and in human colon. Western blot analysis identified Duox2 as the same two molecular species (M(r) 165 and 175 kDa) as detected in the thyroid. It was expressed in all the tissues tested, but the highest levels were found in the cecum and sigmoidal colon. Immunohistochemical studies showed that Duox2 protein is mainly present in these parts of the gut and located at the apical membrane of the enterocytes in the brush border, indicating that it is expressed only in highly differentiated cells. A Ca2+/NADPH-dependent H2O2-generating system was associated with Duox2 protein expression, which had the same biochemical characteristics as the NADPH oxidase in the thyroid. Indeed, treatment of the thyroid and cecum particulate fractions with phenylarsine oxide resulted in complete calcium desensitization of both enzymes. A marked increase in DUOX2 expression was also found during spontaneous differentiation of postconfluent Caco-2 cells. The discovery of Duox2 as a novel source of H2O2 in the digestive tract, particularly in the cecum and colon, makes it a new candidate mediator of physiopathological processes.
authors.affiliation: Unité 486 INSERM, Université Paris 11, Faculté de Pharmacie, 92296 Châtenay-Malabry Cedex, France.
authors.forename: Rabii Ameziane
authors.initials: RA
authors.lastname: El Hassani
authors.forename: Nesrine
authors.initials: N
authors.lastname: Benfares
authors.forename: Bernard
authors.initials: B
authors.lastname: Caillou
authors.forename: Monique
authors.initials: M
authors.lastname: Talbot
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Sabourin
authors.forename: Virginie
authors.initials: V
authors.lastname: Belotte
authors.forename: Stanislas
authors.initials: S
authors.lastname: Morand
authors.forename: Sédami
authors.initials: S
authors.lastname: Gnidehou
authors.forename: Diane
authors.initials: D
authors.lastname: Agnandji
authors.forename: Renée
authors.initials: R
authors.lastname: Ohayon
authors.forename: Jacques
authors.initials: J
authors.lastname: Kaniewski
authors.forename: Marie-Sophie
authors.initials: MS
authors.lastname: Noël-Hudson
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Bidart
authors.forename: Martin
authors.initials: M
authors.lastname: Schlumberger
authors.forename: Alain
authors.initials: A
authors.lastname: Virion
authors.forename: Corinne
authors.initials: C
authors.lastname: Dupuy
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D003106:Colon / Q000201:enzymology; D000074623:Dual Oxidases; D004386:Duodenum / Q000201:enzymology; D005420:Flavoproteins / Q000096:biosynthesis*; D041981:Gastrointestinal Tract / Q000201:enzymology*; D015870:Gene Expression; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007421:Intestine, Small / Q000201:enzymology; D019255:NADPH Oxidases; D013552:Swine; D013961:Thyroid Gland / Q000201:enzymology
chemical_list: D005420:Flavoproteins; D006861:Hydrogen Peroxide; D000074623:Dual Oxidases; D019255:NADPH Oxidases; C431515:DUOX2 protein, human