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Originally published In Press as doi:10.1074/jbc.M000916200 on May 9, 2000

J. Biol. Chem., Vol. 275, Issue 30, 23227-23233, July 28, 2000
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Cloning of Two Human Thyroid cDNAs Encoding New Members of the NADPH Oxidase Family*

Xavier De DekenDagger §, Dantong WangDagger , Marie-Christine Many, Sabine CostagliolaDagger , Frédérick LibertDagger ||, Gilbert VassartDagger **, Jacques E. DumontDagger , and Françoise MiotDagger Dagger Dagger

From the Dagger  Institut de Recherche Interdisciplinaire and ** Service de Génétique Médicale, Hôpital Erasme, Université Libre De Bruxelles, Campus Erasme, 808, route de Lennik, 1070 Bruxelles and  Laboratoire d'Histologie, Université Catholique de Louvain, 1200 Bruxelles, Belgium

Two cDNAs encoding NADPH oxidases and constituting the thyroid H2O2 generating system have been cloned. The strategy of cloning was based on the functional similarities between H2O2 generation in leukocytes and the thyroid, according to the hypothesis that one of the components of the thyroid system would belong to the gp91Phox/Mox1 gene family and display sequence similarities with gp91Phox. Screening at low stringency with a gp91Phox probe of cDNA libraries from thyroid cells in primary culture yielded two distinct human cDNA clones harboring open reading frames of 1551 (ThOX1) and 1548 amino acids (ThOX2), respectively. The encoded polypeptides display 83% sequence similarity and are clearly related to gp91Phox (53 and 47% similarity). The theoretical molecular mass of 177 kDa is close to the apparent molecular mass of 180 kDa of the native corresponding porcine flavoprotein and the protein(s) detected by Western blot in dog and human thyroid. ThOX1 and ThOX2 display sequence similarities of 53% and 61%, respectively, with a predicted protein of Caenorhabditis elegans over their entire length. They show along their first 500 amino acids a similarity of 43% with thyroperoxidase. The corresponding genes of ThOX1 and ThOX2 are closely linked on chromosome 15q15.3. The dog mRNA expression is thyroid-specific and up-regulated by agents activating the cAMP pathway as is the synthesis of the polypeptides they are coding for. In human thyroid the positive regulation by cAMP is less pronounced. The proteins ThOX1 and ThOX2 accumulate at the apical membrane of thyrocytes and are co-localized with thyroperoxidase.

* This work was supported by the Ministère de la Politique Scientifique (Pôle d'Attraction Interuniversitaire), Fonds National de la Recherche Scientifique, Fonds National de la Recherche Scientifique Médicale, Association contre le Cancer, and Association Sportive contre le Cancer.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Fellow of the Fonds pour la Formation à la Recherche dans l'Industrie et l'Agriculture (FRIA).

|| Qualified Researcher of the Belgian Fonds National de la Recherche Scientifique (FNRS).

Dagger Dagger To whom correspondence should be addressed: IRIBHN, Université Libre de Bruxelles, Campus Erasme, Bat. C.; 808, route de Lennik, B-1070 Bruxelles Belgium. Fax: 32-2-5554655; E-mail: fmiot@ulb.ac.be.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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S. Morand, M. Chaaraoui, J. Kaniewski, D. Deme, R. Ohayon, M. S. Noel-Hudson, A. Virion, and C. Dupuy
Effect of Iodide on Nicotinamide Adenine Dinucleotide Phosphate Oxidase Activity and Duox2 Protein Expression in Isolated Porcine Thyroid Follicles
Endocrinology, April 1, 2003; 144(4): 1241 - 1248.
[Abstract] [Full Text] [PDF]

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 J. Clin. Pathol.Home page
P A J Krijnen, C Meischl, C E Hack, C J L M Meijer, C A Visser, D Roos, and H W M Niessen
Increased Nox2 expression in human cardiomyocytes after acute myocardial infarction
J. Clin. Pathol., March 1, 2003; 56(3): 194 - 199.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
S. Morand, O. F. Dos Santos, R. Ohayon, J. Kaniewski, M.-S. Noel-Hudson, A. Virion, and C. Dupuy
Identification of a Truncated Dual Oxidase 2 (DUOX2) Messenger Ribonucleic Acid (mRNA) in Two Rat Thyroid Cell Lines. Insulin and Forskolin Regulation of DUOX2 mRNA Levels in FRTL-5 Cells and Porcine Thyrocytes
Endocrinology, February 1, 2003; 144(2): 567 - 574.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
B. Banfi, R. A. Clark, K. Steger, and K.-H. Krause
Two Novel Proteins Activate Superoxide Generation by the NADPH Oxidase NOX1
J. Biol. Chem., January 31, 2003; 278(6): 3510 - 3513.
[Abstract] [Full Text] [PDF]

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 Arterioscler. Thromb. Vasc. Bio.Home page
N. Kalinina, A. Agrotis, E. Tararak, Y. Antropova, P. Kanellakis, O. Ilyinskaya, M. T. Quinn, V. Smirnov, and A. Bobik
Cytochrome b558-Dependent NAD(P)H Oxidase-Phox Units in Smooth Muscle and Macrophages of Atherosclerotic Lesions
Arterioscler. Thromb. Vasc. Biol., December 1, 2002; 22(12): 2037 - 2043.
[Abstract] [Full Text] [PDF]

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 J. Clin. Pathol.Home page
L Van Heerebeek, C Meischl, W Stooker, C J L M Meijer, H W M Niessen, and D Roos
NADPH oxidase(s): new source(s) of reactive oxygen species in the vascular system?
J. Clin. Pathol., August 1, 2002; 55(8): 561 - 568.
[Abstract] [Full Text] [PDF]

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 NEJMHome page
J. C. Moreno, H. Bikker, M. J.E. Kempers, A.S. P. van Trotsenburg, F. Baas, J. J.M. de Vijlder, T. Vulsma, and C. Ris-Stalpers
Inactivating Mutations in the Gene for Thyroid Oxidase 2 (THOX2) and Congenital Hypothyroidism
N. Engl. J. Med., July 11, 2002; 347(2): 95 - 102.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
P. Kopp
Perspective: Genetic Defects in the Etiology of Congenital Hypothyroidism
Endocrinology, June 1, 2002; 143(6): 2019 - 2024.
[Abstract] [Full Text] [PDF]

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 Toxicol SciHome page
A. Deshpande, P. K. Narayanan, and B. E. Lehnert
Silica-Induced Generation of Extracellular Factor(s) Increases Reactive Oxygen Species in Human Bronchial Epithelial Cells
Toxicol. Sci., June 1, 2002; 67(2): 275 - 283.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
J. W. A. Smit, J. P. Schroder-van der Elst, M. Karperien, I. Que, M. Stokkel, D. van der Heide, and J. A. Romijn
Iodide Kinetics and Experimental 131I Therapy in a Xenotransplanted Human Sodium-Iodide Symporter-Transfected Human Follicular Thyroid Carcinoma Cell Line
J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1247 - 1253.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
A.-C. Gerard, M.-C. Many, C. Daumerie, S. Costagliola, F. Miot, J. J. M. DeVijlder, I. M. Colin, and J.-F. Denef
Structural Changes in the Angiofollicular Units between Active and Hypofunctioning Follicles Align with Differences in the Epithelial Expression of Newly Discovered Proteins Involved in Iodine Transport and Organification
J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1291 - 1299.
[Abstract] [Full Text] [PDF]

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 Exp. Biol. Med.Home page
M. Sugawara, Y. Sugawara, K. Wen, and C. Giulivi
Generation of Oxygen Free Radicals in Thyroid Cells and Inhibition of Thyroid Peroxidase
Experimental Biology and Medicine, February 1, 2002; 227(2): 141 - 146.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
M. D. L. Figueiredo, L. C. Cardoso, A. C. F. Ferreira, D. V. B. Campos, M. da Cruz Domingos, R. Corbo, L. E. Nasciutti, M. Vaisman, and D. P. Carvalho
Goiter and Hypothyroidism in Two Siblings due to Impaired Ca+2/NAD(P)H-Dependent H2O2-Generating Activity
J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4843 - 4848.
[Abstract] [Full Text] [PDF]

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 Biol. Reprod.Home page
P. Vernet, N. Fulton, C. Wallace, and R. J. Aitken
Analysis of Reactive Oxygen Species Generating Systems in Rat Epididymal Spermatozoa
Biol Reprod, October 1, 2001; 65(4): 1102 - 1113.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
L. C. Cardoso, D. C. L. Martins, M. D. L. Figueiredo, D. Rosenthal, M. Vaisman, A. H. D. Violante, and D. P. Carvalho
Ca2+/Nicotinamide Adenine Dinucleotide Phosphate-Dependent H2O2 Generation Is Inhibited by Iodide in Human Thyroids
J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4339 - 4343.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
T. Kawahara, S. Teshima, A. Oka, T. Sugiyama, K. Kishi, and K. Rokutan
Type I Helicobacter pylori Lipopolysaccharide Stimulates Toll-Like Receptor 4 and Activates Mitogen Oxidase 1 in Gastric Pit Cells
Infect. Immun., July 1, 2001; 69(7): 4382 - 4389.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
B. Caillou, C. Dupuy, L. Lacroix, M. Nocera, M. Talbot, R. Ohayon, D. Deme, J.-M. Bidart, M. Schlumberger, and A. Virion.
Expression of Reduced Nicotinamide Adenine Dinucleotide Phosphate Oxidase (ThoX, LNOX, Duox) Genes and Proteins in Human Thyroid Tissues
J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3351 - 3358.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
R. S. Arnold, J. Shi, E. Murad, A. M. Whalen, C. Q. Sun, R. Polavarapu, S. Parthasarathy, J. A. Petros, and J. D. Lambeth
Hydrogen peroxide mediates the cell growth and transformation caused by the mitogenic oxidase Nox1
PNAS, April 25, 2001; (2001) 101505898.
[Abstract] [Full Text]

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 Am. J. Physiol. Heart Circ. Physiol.Home page
H. P. Souza, F. R. M. Laurindo, R. C. Ziegelstein, C. O. Berlowitz, and J. L. Zweier
Vascular NAD(P)H oxidase is distinct from the phagocytic enzyme and modulates vascular reactivity control
Am J Physiol Heart Circ Physiol, February 1, 2001; 280(2): H658 - H667.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
B. Bakker, H. Bikker, T. Vulsma, J. S. E. de Randamie, B. M. Wiedijk, and J. J. M. de Vijlder
Two Decades of Screening for Congenital Hypothyroidism in the Netherlands: TPO Gene Mutations in Total Iodide Organification Defects (an Update)
J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3708 - 3712.
[Abstract] [Full Text]

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 J. Biol. Chem.Home page
J. M. Larios, R. Budhiraja, B. L. Fanburg, and V. J. Thannickal
Oxidative Protein Cross-linking Reactions Involving L-Tyrosine in Transforming Growth Factor-beta 1-stimulated Fibroblasts
J. Biol. Chem., May 11, 2001; 276(20): 17437 - 17441.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
S. Sanlioglu, C. M. Williams, L. Samavati, N. S. Butler, G. Wang, P. B. McCray Jr., T. C. Ritchie, G. W. Hunninghake, E. Zandi, and J. F. Engelhardt
Lipopolysaccharide Induces Rac1-dependent Reactive Oxygen Species Formation and Coordinates Tumor Necrosis Factor-alpha Secretion through IKK Regulation of NF-kappa B
J. Biol. Chem., August 3, 2001; 276(32): 30188 - 30198.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
W.-G. Li, F. J. Miller Jr., H. J. Zhang, D. R. Spitz, L. W. Oberley, and N. L. Weintraub
H2O2-induced O-.2 Production by a Non-phagocytic NAD(P)H Oxidase Causes Oxidant Injury
J. Biol. Chem., July 27, 2001; 276(31): 29251 - 29256.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
B. Banfi, G. Molnar, A. Maturana, K. Steger, B. Hegedus, N. Demaurex, and K.-H. Krause
A Ca2+-activated NADPH Oxidase in Testis, Spleen, and Lymph Nodes
J. Biol. Chem., September 28, 2001; 276(40): 37594 - 37601.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
R. S. Arnold, J. Shi, E. Murad, A. M. Whalen, C. Q. Sun, R. Polavarapu, S. Parthasarathy, J. A. Petros, and J. D. Lambeth
Hydrogen peroxide mediates the cell growth and transformation caused by the mitogenic oxidase Nox1
PNAS, May 8, 2001; 98(10): 5550 - 5555.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. S. Brar, T. P. Kennedy, A. B. Sturrock, T. P. Huecksteadt, M. T. Quinn, T. M. Murphy, P. Chitano, and J. R. Hoidal
NADPH oxidase promotes NF-kappa B activation and proliferation in human airway smooth muscle
Am J Physiol Lung Cell Mol Physiol, April 1, 2002; 282(4): L782 - L795.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
B. Lassegue, D. Sorescu, K. Szocs, Q. Yin, M. Akers, Y. Zhang, S. L. Grant, J. D. Lambeth, and K. K. Griendling
Novel gp91phox Homologues in Vascular Smooth Muscle Cells : nox1 Mediates Angiotensin II-Induced Superoxide Formation and Redox-Sensitive Signaling Pathways
Circ. Res., May 11, 2001; 88(9): 888 - 894.
[Abstract] [Full Text] [PDF]


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