Disease relevance of DUOX1

• We investigated both DUOX1 and DUOX2 gene expressions using quantitative reverse transcription-polymerase chain reaction (RT-PCR) in 47 thyroid carcinomas, including 10 paired normal/tumoral tissues [1].
• The identification of DUOXA genes has important implications for studies of the molecular mechanisms controlling DUOX expression and the molecular genetics of congenital hypothyroidism [2].
• The H(2)O(2)-generating system, ThOXs, was found in all carcinomas and was even increased in papillary carcinomas [3].
• In hypofunctioning adenomas, LNOX immunostaining was highly variable among follicles, whereas sodium/iodide (Na+/I-) symporter immunostaining was decreased [4].
• Subjects with mild/moderate COPD, who were all former smokers, exhibited downregulation of bronchiolar Duox1 and Duox2 when compared to individuals who have never smoked, whereas a difference between former smokers, with and without COPD, was observed only for Duox1 [5].

Psychiatry related information on DUOX1

• Our observations suggest that Duox1 and Duox2 are novel H2O2 sources that can support LPO-mediated antimicrobial defense mechanisms on mucosal surfaces [6].

High impact information on DUOX1

• Thus, Ce-Duox catalyzes the cross-linking of tyrosine residues involved in the stabilization of cuticular extracellular matrix [7].
• Dual oxidase 1-dependent MUC5AC mucin expression in cultured human airway epithelial cells [8].
• Furthermore, the PKCdelta/PKC inhibitor rottlerin prevented the effects induced by phorbol 12-myristate 13-acetate and human neutrophil elastase, suggesting that PKCdelta and PKC are involved in Duox1 activation [8].
• Dual oxidase 1 (Duox1), a homologue of glycoprotein p91(phox), is expressed in airway epithelium and generates ROS [8].
• Here, we report a critical role for dual oxidase 1 (Duox1), a newly identified NADPH oxidase homolog within the tracheobronchial epithelium, in airway epithelial cell migration and repair following injury [9].

Chemical compound and disease context of DUOX1

• Expression of nicotinamide adenine dinucleotide phosphate oxidase flavoprotein DUOX genes and proteins in human papillary and follicular thyroid carcinomas [1].
• We hypothesized that molecular defects in the thyroid oxidase system, which is composed of at least two proteins, might be involved in the pathogenesis of permanent or transient congenital hypothyroidism in babies with defects in iodide organification, for which the oxidase system is required [10].

Biological context of DUOX1

• Identification of the maturation factor for dual oxidase. Evolution of an eukaryotic operon equivalent [2].
• Northern blot analysis of 23 different human tissues demonstrated that LNOX2 messenger RNA (mRNA) is strongly expressed only in the thyroid gland, although blast analysis of expressed sequence tags databases indicated that LNOX genes are also expressed in some nonthyroid cells [4].
• ATP and thapsigargin increased intracellular Ca(2+) with kinetics similar to increasing H(2)O(2) production, and thus consistent with the expected Ca(2+) sensitivity of Duox [11].
• RNA interference of dual oxidase in the plant nematode Meloidogyne incognita [12].

Anatomical context of DUOX1

• So far, because of the impairment of maturation and of the targeting process, transfecting DUOX into nonthyroid cell lines has not led to the expression of a functional H2O2-generating system at the plasma membrane [13].
• Since it was found in the intestine, duodenum, and colon, in addition to thyroid, we suggest that it be called LNOX, the new family of long homologs of NOX flavoproteins rather than THOX and/or DUOX [14].
• It has been proposed that DUOX retention in the endoplasmatic reticulum (ER) of heterologous systems is due to the lack of an unidentified component required for functional maturation of the enzyme [2].
• Furthermore, we detected Duox1-dependent H2O2 release by cultured human bronchial epithelial cells [6].
• We examined Duox1 and Duox2 expression in secretory glands and on mucosal surfaces and give evidence for their presence and activity in salivary glands, rectum, trachea, and bronchium [6].

Associations of DUOX1 with chemical compounds

• Duox2 (and probably Duox1) is a glycoflavoprotein involved in thyroid hormone biosynthesis, as the thyroid H2O2 generator functionally associated with Tpo (thyroperoxidase) [13].
• The particulate fractions of these cells stably or transiently transfected with human or porcine DUOX cDNA demonstrate a functional NADPH/Ca2+-dependent H2O2-generating activity [13].
• The level of THOX2 mRNA was increased by cAMP in these cells and it was decreased in the thyroids of rats treated with the antithyroid drug methimazole, unlike the TPO and NIS mRNAs [14].
• ThOX proteins (thyroid oxidase) also called Duox are believed to be responsible for H(2)O(2) generation [15].
• Expression of reduced nicotinamide adenine dinucleotide phosphate oxidase (ThoX, LNOX, Duox) genes and proteins in human thyroid tissues [4].
• Although the activation domain of Noxa1 was not required for Duox function, mutation of a proline-rich domain in the Duox C terminus, a potential interaction motif for the Noxa1 Src homology domain 3, caused up-regulation of basal and stimulated H2O2 production [16].

Other interactions of DUOX1

• In the 10 paired samples, variations of DUOX and TPO gene expressions were not correlated [1].
• EFP1 and Duox mRNA share similar distribution in nine different tissues [15].
• However, no functional DUOX-based NADPH oxidase has ever been reconstituted at the plasma membrane of transfected cells [2].
• By data mining of a massively parallel signature sequencing tissue expression data base, we identified an uncharacterized gene named DUOX maturation factor (DUOXA2) arranged head-to-head to and co-expressed with DUOX2 [2].
• Homologues of gp91phox, called Nox and Duox, are present in a large variety of non-phagocytic cells [17].

Analytical, diagnostic and therapeutic context of DUOX1

• To investigate the source of H(2)O(2) produced by airway epithelia, PCR was used to screen nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression in human airway epithelia redifferentiated at the air-liquid interface (ALI) and demonstrated the presence of Duox1 and 2 [11].
• Western blots of culture extracts indicated strong expression of Duox, and immunohistochemistry of human tracheal sections localized the protein to the apical portion of epithelial cells [11].

References