Dual oxidase2 is expressed all along the digestive tract.
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.
El Hassani
Rabii Ameziane
RA
Unité 486 INSERM, Université Paris 11, Faculté de Pharmacie, 92296 Châtenay-Malabry Cedex, France.
Benfares
Nesrine
N
Caillou
Bernard
B
Talbot
Monique
M
Sabourin
Jean-Christophe
JC
Belotte
Virginie
V
Morand
Stanislas
S
Gnidehou
Sédami
S
Agnandji
Diane
D
Ohayon
Renée
R
Kaniewski
Jacques
J
Noël-Hudson
Marie-Sophie
MS
Bidart
Jean-Michel
JM
Schlumberger
Martin
M
Virion
Alain
A
Dupuy
Corinne
C
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
D005420:Flavoproteins; D006861:Hydrogen Peroxide; D000074623:Dual Oxidases; D019255:NADPH Oxidases; C431515:DUOX2 protein, human