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.

NADPH oxidases in lung biology and pathology: Host defense enzymes, and more

“…The importance of DUOX2 in thyroid hormone synthesis is supported by clinical observations of hypothyroidism in association with missense mutations in the DUOX2 gene (28,29). DUOX1 and 2 are also expressed in airway and intestinal epithelia, where they may contribute to host defense by a similar cooperative mechanism with lactoperoxidase (LPO), which is secreted by submucosal glands (1,30,31). A structurally related dual oxidase, Udx1, is expressed in sea urchin eggs and is activated upon fertilization to produce H 2 O 2 which stimulates ovoperoxidase-mediated protein cross-linking within the fertilization envelope (32).…”

Caenorhabditis elegans and Human Dual Oxidase 1 (DUOX1) “Peroxidase” Domains

“…When mutated in such enzymes as horseradish peroxidase, cytochrome c peroxidase, and dehaloperoxidase, a significant loss of activity is observed (42)(43)(44)(45)(46). This fact has led researchers to postulate that the N-terminal region of DUOX1 may not act as a classical peroxidase but rather as a SOD (8,12). In an effort to clarify the function of these domains, now available as purified and structurally sound proteins, we examined each homolog with regard to its peroxidase and SOD activity.…”

“…DUOX1 and 2 (formerly also known as ThOX1 and 2 for thyroid oxidase) were first identified in the mammalian thyroid gland (9,10). This localization is not exclusive because both can also be found in nonthyroid tissues; DUOX1 is prominent in airway epithelial cells (11) and DUOX2 in the salivary glands and gastrointestinal tract (4,12,13). Homologs of each DUOX have also been identified in lower organisms, including Caenorhabditis elegans and Drosophila melanogaster (14).…”

The dual oxidase gene BdDuox regulates the intestinal bacterial community homeostasis of Bactrocera dorsalis

“…Interestingly, the diverse NOX and DUOX family enzymes are not only expressed in phagocytic cells, but also in various nonphagocytic cells, including mucosal epithelial cells (Ha et al, 2005;Allaoui et al, 2009;Fischer, 2009), indicating their potential biological roles in these cells. In addition, several recent studies have shown that ROS are microbicidal effector molecules in the gut epithelia (El Hassani et al, 2005;Ha et al, 2005Ha et al, , 2009a. In Drosophila, there is only one Duox gene and one Nox gene in the genome, and genetic analysis has shown that Duox-knockout flies, but not Nox-knockout flies, cannot produce infection-induced ROS (Ha et al, 2005).…”