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Am J Physiol Gastrointest Liver Physiol (December 9, 2004). doi:10.1152/ajpgi.00198.2004
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Submitted on April 29, 2004
Accepted on November 23, 2004

Dual oxidase2 is expressed all along the digestive tract

Rabii Ameziane El Hassani1, Nesrine Benfares1, Bernard Caillou2, Monique Talbot2, Jean-Christophe Sabourin2, Virginie Belotte2, Stanislas Morand1, Sedami Gnidehou1, Diane Agnandji1, Renee Ohayon1, Jacques Kaniewski1, Marie-Sophie Noel-Hudson1, Jean-Michel Bidart2, Martin Schlumberger2, Alain Virion1, and Corinne Dupuy1*

1 Faculte de Pharmacie, Unite 486 Inserm, Universite Paris 11, Chatenay-Malabry, France
2 UMR 8125 CNRS/CEA LRC 29V, Institut Gustave-Roussy, Villejuif, France

* To whom correspondence should be addressed. E-mail: corinne.dupuy{at}cep.u-psud.fr.

The Duox2 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 (Mr 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 caecum 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 caecum particulate fractions with phenylarsine oxide (PAO) resulted in complete calcium-desensitization of both enzymes. A marked increase in DUOX2 expression was also found during spontaneous differentiation of post-confluent Caco-2 cells. The discovery of Duox2 as a novel source of H2O2 in the digestive tract, particularly in the caecum and colon, makes it a new candidate mediator of physiopathological processes.




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