“Dual oxidase 2”的意思、由来-开放百科全书

Function

Investigations into reactive oxygen species (ROS) in biological systems have, until recently, focused on characterization of phagocytic cell processes. It is now well accepted that production of such species is not restricted to phagocytic cells and can occur in eukaryotic non-phagocytic cell types via NADPH oxidase (NOX) or dual oxidase (DUOX). This new family of proteins, termed the NOX/DUOX family or NOX family of NADPH oxidases, consists of homologs to the catalytic moiety of phagocytic NADPH-oxidase, gp91^phox. Members of the NOX/DUOX family have been found throughout eukaryotic species, including invertebrates, insects, nematodes, fungi, amoeba, alga, and plants (not found in prokaryotes). These enzymes clearly demonstrate regulated production of ROS as their sole function. Genetic analyses have implicated NOX/DUOX derived ROS in biological roles and pathological conditions including hypertension (NOX1), innate immunity (NOX2/DUOX), otoconia formation in the inner ear (NOX3) and thyroid hormone biosynthesis (DUOX1/2). It has been suggested that DUOX2 is the isoform to generate H₂O₂ utilized by thyroid peroxidase (TPO) for the biosynthesis of thyroid hormones, supported by the discovery of congenital hypothyroidism resultant from an inactivating mutation in the DUOX2 gene.^[1]^[7]

The family currently has seven members including NOX1, NOX2 (formerly known as gp91^phox), NOX3, NOX4, NOX5, DUOX1 and DUOX2.

This protein is known as a dual oxidase because it has both a peroxidase homology domain and a gp91^phox domain.^[8]

Duox are also implicated in lung defence system^[9] and especially in cystic fibrosis.^[10]^[11]^[12]

Schema of duox implication in human lung defence system

References

1. ^¹{{cite journal | vauthors = Dupuy C, Ohayon R, Valent A, Noël-Hudson MS, Dème D, Virion A | title = Purification of a novel flavoprotein involved in the thyroid NADPH oxidase. Cloning of the porcine and human cdnas | journal = J. Biol. Chem. | volume = 274 | issue = 52 | pages = 37265–9 | date = December 1999 | pmid = 10601291 | doi = 10.1074/jbc.274.52.37265 }}
2. ^{{cite journal | vauthors = De Deken X, Wang D, Many MC, Costagliola S, Libert F, Vassart G, Dumont JE, Miot F | title = Cloning of two human thyroid cDNAs encoding new members of the NADPH oxidase family | journal = J. Biol. Chem. | volume = 275 | issue = 30 | pages = 23227–33 | date = July 2000 | pmid = 10806195 | doi = 10.1074/jbc.M000916200}}
3. ^{{cite journal | vauthors = Harper RW, Xu C, Eiserich JP, Chen Y, Kao CY, Thai P, Setiadi H, Wu R | title = Differential regulation of dual NADPH oxidases/peroxidases, Duox1 and Duox2, by Th1 and Th2 cytokines in respiratory tract epithelium | journal = FEBS Lett. | volume = 579 | issue = 21 | pages = 4911–7 | date = August 2005 | pmid = 16111680 | doi = 10.1016/j.febslet.2005.08.002}}
4. ^{{cite journal | vauthors = Geiszt M, Witta J, Baffi J, Lekstrom K, Leto TL | title = Dual oxidases represent novel hydrogen peroxide sources supporting mucosal surface host defense | journal = FASEB J. | volume = 17 | issue = 11 | pages = 1502–4 | date = August 2003 | pmid = 12824283 | doi = 10.1096/fj.02-1104fje}}
5. ^{{cite journal | vauthors = El Hassani RA, Benfares N, Caillou B, Talbot M, Sabourin JC, Belotte V, Morand S, Gnidehou S, Agnandji D, Ohayon R, Kaniewski J, Noël-Hudson MS, Bidart JM, Schlumberger M, Virion A, Dupuy C | title = Dual oxidase2 is expressed all along the digestive tract | journal = Am. J. Physiol. Gastrointest. Liver Physiol. | volume = 288 | issue = 5 | pages = G933–42 | date = May 2005 | pmid = 15591162 | doi = 10.1152/ajpgi.00198.2004| citeseerx = 10.1.1.334.1785 }}
6. ^{{cite journal | vauthors = Rokutan K, Kawahara T, Kuwano Y, Tominaga K, Nishida K, Teshima-Kondo S | title = Nox enzymes and oxidative stress in the immunopathology of the gastrointestinal tract | journal = Semin Immunopathol | volume = 30 | issue = 3 | pages = 315–27 | date = July 2008 | pmid = 18521607 | doi = 10.1007/s00281-008-0124-5 }}
7. ^{{cite journal | vauthors = Moreno JC, Bikker H, Kempers MJ, van Trotsenburg AS, Baas F, de Vijlder JJ, Vulsma T, Ris-Stalpers C | title = Inactivating mutations in the gene for thyroid oxidase 2 (THOX2) and congenital hypothyroidism | journal = N. Engl. J. Med. | volume = 347 | issue = 2 | pages = 95–102 | date = July 2002 | pmid = 12110737 | doi = 10.1056/NEJMoa012752}}
8. ^{{cite web | title = Entrez Gene: DUOX2 dual oxidase 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=50506| accessdate = }}
9. ^{{cite journal | vauthors = Fischer H | title = Mechanisms and function of DUOX in epithelia of the lung | journal = Antioxid. Redox Signal. | volume = 11 | issue = 10 | pages = 2453–65 | date = October 2009 | pmid = 19358684 | pmc = 2823369 | doi = 10.1089/ARS.2009.2558}}
10. ^{{cite journal | vauthors = Rada B, Lekstrom K, Damian S, Dupuy C, Leto TL | title = The Pseudomonas toxin pyocyanin inhibits the dual oxidase-based antimicrobial system as it imposes oxidative stress on airway epithelial cells | journal = J. Immunol. | volume = 181 | issue = 7 | pages = 4883–93 | date = October 2008 | pmid = 18802092 | pmc = 2776642 | doi = 10.4049/jimmunol.181.7.4883}}
11. ^{{cite journal | vauthors = Conner GE, Salathe M, Forteza R | title = Lactoperoxidase and hydrogen peroxide metabolism in the airway | journal = Am. J. Respir. Crit. Care Med. | volume = 166 | issue = 12 Pt 2 | pages = S57–61 | date = December 2002 | pmid = 12471090 | doi = 10.1164/rccm.2206018}}
12. ^{{cite book | vauthors = Rada B, Leto TL | title = Oxidative innate immune defenses by Nox/Duox family NADPH oxidases | journal = Contrib Microbiol | volume = 15 | pages = 164–87 | year = 2008 | pmid = 18511861 | pmc = 2776633 | doi = 10.1159/000136357| series = Contributions to Microbiology | isbn = 978-3-8055-8548-4 }}

Further reading

{{cite journal | vauthors = Lambeth JD | title = Nox/Duox family of nicotinamide adenine dinucleotide (phosphate) oxidases. | journal = Curr. Opin. Hematol. | volume = 9 | issue = 1 | pages = 11–7 | year = 2002 | pmid = 11753072 | doi = 10.1097/00062752-200201000-00003 }}

{{cite book | vauthors = Moreno JC, Visser TJ | title = New phenotypes in thyroid dyshormonogenesis: hypothyroidism due to DUOX2 mutations. | journal = Endocrine Development | volume = 10 | pages = 99–117 | year = 2007 | pmid = 17684392 | doi = 10.1159/000106822 | isbn = 978-3-8055-8075-5 }}

{{cite journal | vauthors = Dupuy C, Ohayon R, Valent A, Noël-Hudson MS, Dème D, Virion A | title = Purification of a novel flavoprotein involved in the thyroid NADPH oxidase. Cloning of the porcine and human cdnas. | journal = J. Biol. Chem. | volume = 274 | issue = 52 | pages = 37265–9 | year = 2000 | pmid = 10601291 | doi = 10.1074/jbc.274.52.37265 }}

{{cite journal | vauthors = Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, Zago MA, Bordin S, Costa FF, Goldman GH, Carvalho AF, Matsukuma A, Baia GS, Simpson DH, Brunstein A, de Oliveira PS, Bucher P, Jongeneel CV, O'Hare MJ, Soares F, Brentani RR, Reis LF, de Souza SJ, Simpson AJ | title = Shotgun sequencing of the human transcriptome with ORF expressed sequence tags. | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 97 | issue = 7 | pages = 3491–6 | year = 2000 | pmid = 10737800 | pmc = 16267 | doi = 10.1073/pnas.97.7.3491 }}

{{cite journal | vauthors = De Deken X, Wang D, Many MC, Costagliola S, Libert F, Vassart G, Dumont JE, Miot F | title = Cloning of two human thyroid cDNAs encoding new members of the NADPH oxidase family. | journal = J. Biol. Chem. | volume = 275 | issue = 30 | pages = 23227–33 | year = 2000 | pmid = 10806195 | doi = 10.1074/jbc.M000916200 }}

{{cite journal | vauthors = Dupuy C, Pomerance M, Ohayon R, Noël-Hudson MS, Dème D, Chaaraoui M, Francon J, Virion A | title = Thyroid oxidase (THOX2) gene expression in the rat thyroid cell line FRTL-5. | journal = Biochem. Biophys. Res. Commun. | volume = 277 | issue = 2 | pages = 287–92 | year = 2000 | pmid = 11032719 | doi = 10.1006/bbrc.2000.3671 }}

{{cite journal | vauthors = Caillou B, Dupuy C, Lacroix L, Nocera M, Talbot M, Ohayon R, Dème D, Bidart JM, Schlumberger M, Virion A | title = Expression of reduced nicotinamide adenine dinucleotide phosphate oxidase (ThoX, LNOX, Duox) genes and proteins in human thyroid tissues. | journal = J. Clin. Endocrinol. Metab. | volume = 86 | issue = 7 | pages = 3351–8 | year = 2001 | pmid = 11443211 | doi = 10.1210/jc.86.7.3351 }}

{{cite journal | vauthors = Edens WA, Sharling L, Cheng G, Shapira R, Kinkade JM, Lee T, Edens HA, Tang X, Sullards C, Flaherty DB, Benian GM, Lambeth JD | title = Tyrosine cross-linking of extracellular matrix is catalyzed by Duox, a multidomain oxidase/peroxidase with homology to the phagocyte oxidase subunit gp91phox. | journal = J. Cell Biol. | volume = 154 | issue = 4 | pages = 879–91 | year = 2001 | pmid = 11514595 | pmc = 2196470 | doi = 10.1083/jcb.200103132 }}

{{cite journal | vauthors = Lacroix L, Nocera M, Mian C, Caillou B, Virion A, Dupuy C, Filetti S, Bidart JM, Schlumberger M | title = Expression of nicotinamide adenine dinucleotide phosphate oxidase flavoprotein DUOX genes and proteins in human papillary and follicular thyroid carcinomas. | journal = Thyroid | volume = 11 | issue = 11 | pages = 1017–23 | year = 2002 | pmid = 11762710 | doi = 10.1089/105072501753271699 }}

{{cite journal | vauthors = De Deken X, Wang D, Dumont JE, Miot F | title = Characterization of ThOX proteins as components of the thyroid H(2)O(2)-generating system. | journal = Exp. Cell Res. | volume = 273 | issue = 2 | pages = 187–96 | year = 2002 | pmid = 11822874 | doi = 10.1006/excr.2001.5444 }}

{{cite journal | vauthors = Moreno JC, Bikker H, Kempers MJ, van Trotsenburg AS, Baas F, de Vijlder JJ, Vulsma T, Ris-Stalpers C | title = Inactivating mutations in the gene for thyroid oxidase 2 (THOX2) and congenital hypothyroidism. | journal = N. Engl. J. Med. | volume = 347 | issue = 2 | pages = 95–102 | year = 2002 | pmid = 12110737 | doi = 10.1056/NEJMoa012752 }}

{{cite journal | vauthors = Geiszt M, Witta J, Baffi J, Lekstrom K, Leto TL | title = Dual oxidases represent novel hydrogen peroxide sources supporting mucosal surface host defense. | journal = FASEB J. | volume = 17 | issue = 11 | pages = 1502–4 | year = 2003 | pmid = 12824283 | doi = 10.1096/fj.02-1104fje }}

{{cite journal | vauthors = Pachucki J, Wang D, Christophe D, Miot F | title = Structural and functional characterization of the two human ThOX/Duox genes and their 5'-flanking regions. | journal = Mol. Cell. Endocrinol. | volume = 214 | issue = 1–2 | pages = 53–62 | year = 2004 | pmid = 15062544 | doi = 10.1016/j.mce.2003.11.026 }}

{{cite journal | vauthors = Morand S, Agnandji D, Noel-Hudson MS, Nicolas V, Buisson S, Macon-Lemaitre L, Gnidehou S, Kaniewski J, Ohayon R, Virion A, Dupuy C | title = Targeting of the dual oxidase 2 N-terminal region to the plasma membrane. | journal = J. Biol. Chem. | volume = 279 | issue = 29 | pages = 30244–51 | year = 2004 | pmid = 15150274 | doi = 10.1074/jbc.M405406200 }}

{{cite journal | vauthors = Schwarzer C, Machen TE, Illek B, Fischer H | title = NADPH oxidase-dependent acid production in airway epithelial cells. | journal = J. Biol. Chem. | volume = 279 | issue = 35 | pages = 36454–61 | year = 2004 | pmid = 15210697 | doi = 10.1074/jbc.M404983200 }}

{{cite journal | vauthors = Wang D, De Deken X, Milenkovic M, Song Y, Pirson I, Dumont JE, Miot F | title = Identification of a novel partner of duox: EFP1, a thioredoxin-related protein. | journal = J. Biol. Chem. | volume = 280 | issue = 4 | pages = 3096–103 | year = 2005 | pmid = 15561711 | doi = 10.1074/jbc.M407709200 }}

{{cite journal | vauthors = El Hassani RA, Benfares N, Caillou B, Talbot M, Sabourin JC, Belotte V, Morand S, Gnidehou S, Agnandji D, Ohayon R, Kaniewski J, Noël-Hudson MS, Bidart JM, Schlumberger M, Virion A, Dupuy C | title = Dual oxidase2 is expressed all along the digestive tract. | journal = Am. J. Physiol. Gastrointest. Liver Physiol. | volume = 288 | issue = 5 | pages = G933–42 | year = 2005 | pmid = 15591162 | doi = 10.1152/ajpgi.00198.2004 | citeseerx = 10.1.1.334.1785 }}

{{cite journal | vauthors = Forteza R, Salathe M, Miot F, Forteza R, Conner GE | title = Regulated hydrogen peroxide production by Duox in human airway epithelial cells. | journal = Am. J. Respir. Cell Mol. Biol. | volume = 32 | issue = 5 | pages = 462–9 | year = 2005 | pmid = 15677770 | doi = 10.1165/rcmb.2004-0302OC }}

{{cite journal | vauthors = Ameziane-El-Hassani R, Morand S, Boucher JL, Frapart YM, Apostolou D, Agnandji D, Gnidehou S, Ohayon R, Noël-Hudson MS, Francon J, Lalaoui K, Virion A, Dupuy C | title = Dual oxidase-2 has an intrinsic Ca2+-dependent H2O2-generating activity. | journal = J. Biol. Chem. | volume = 280 | issue = 34 | pages = 30046–54 | year = 2005 | pmid = 15972824 | doi = 10.1074/jbc.M500516200 }}

1 : EF-hand-containing proteins