Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1999 Jul 1;341(Pt 1):71–80.

Molecular cloning of the cDNA coding for mouse aldehyde oxidase: tissue distribution and regulation in vivo by testosterone.

M Kurosaki 1, S Demontis 1, M M Barzago 1, E Garattini 1, M Terao 1
PMCID: PMC1220331  PMID: 10377246

Abstract

The cDNA coding for mouse aldehyde oxidase (AO), a molybdoflavoprotein, has been isolated and characterized. The cDNA is 4347 nt long and consists of an open reading frame predicting a polypeptide of 1333 amino acid residues, with 5' and 3' untranslated regions of 13 and 335 nt respectively. The apparent molecular mass of the translation product in vitro derived from the corresponding cRNA is consistent with that of the monomeric subunit of the AO holoenzyme. The cDNA codes for a catalytically active form of AO, as demonstrated by transient transfection experiments conducted in the HC11 mouse mammary epithelial cell line. The deduced primary structure of the AO protein contains consensus sequences for two distinct 2Fe-2S redox centres and a molybdopterin-binding site. The amino acid sequence of the mouse AO has a high degree of similarity with the human and bovine counterparts, and a significant degree of relatedness to AO proteins of plant origin. Northern blot and in situ hybridization analyses demonstrate that hepatocytes, cardiocytes, lung endothelial or epithelial cells and oesophagus epithelial cells express high levels of AO mRNA. In the various tissues and organs considered, the level of AO mRNA expression is not strictly correlated with the amount of the corresponding protein, suggesting that the synthesis of the AO enzyme is under translational or post-translational control. In addition, we observed sex-related regulation of AO protein synthesis. In the liver of male animals, despite similar amounts of AO mRNA, the levels of the AO enzyme and corresponding polypeptide are significantly higher than those in female animals. Treatment of female mice with testosterone increases the amounts of AO mRNA and of the relative translation product to levels similar to those in male animals.

Full Text

The Full Text of this article is available as a PDF (416.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amaya Y., Yamazaki K., Sato M., Noda K., Nishino T., Nishino T. Proteolytic conversion of xanthine dehydrogenase from the NAD-dependent type to the O2-dependent type. Amino acid sequence of rat liver xanthine dehydrogenase and identification of the cleavage sites of the enzyme protein during irreversible conversion by trypsin. J Biol Chem. 1990 Aug 25;265(24):14170–14175. [PubMed] [Google Scholar]
  2. Bendotti C., Prosperini E., Kurosaki M., Garattini E., Terao M. Selective localization of mouse aldehyde oxidase mRNA in the choroid plexus and motor neurons. Neuroreport. 1997 Jul 7;8(9-10):2343–2349. doi: 10.1097/00001756-199707070-00048. [DOI] [PubMed] [Google Scholar]
  3. Berger R., Mezey E., Clancy K. P., Harta G., Wright R. M., Repine J. E., Brown R. H., Brownstein M., Patterson D. Analysis of aldehyde oxidase and xanthine dehydrogenase/oxidase as possible candidate genes for autosomal recessive familial amyotrophic lateral sclerosis. Somat Cell Mol Genet. 1995 Mar;21(2):121–131. doi: 10.1007/BF02255787. [DOI] [PubMed] [Google Scholar]
  4. Berglund L., Rasmussen J. T., Andersen M. D., Rasmussen M. S., Petersen T. E. Purification of the bovine xanthine oxidoreductase from milk fat globule membranes and cloning of complementary deoxyribonucleic acid. J Dairy Sci. 1996 Feb;79(2):198–204. doi: 10.3168/jds.S0022-0302(96)76351-8. [DOI] [PubMed] [Google Scholar]
  5. Calzi M. L., Raviolo C., Ghibaudi E., de Gioia L., Salmona M., Cazzaniga G., Kurosaki M., Terao M., Garattini E. Purification, cDNA cloning, and tissue distribution of bovine liver aldehyde oxidase. J Biol Chem. 1995 Dec 29;270(52):31037–31045. doi: 10.1074/jbc.270.52.31037. [DOI] [PubMed] [Google Scholar]
  6. Cazzaniga G., Terao M., Lo Schiavo P., Galbiati F., Segalla F., Seldin M. F., Garattini E. Chromosomal mapping, isolation, and characterization of the mouse xanthine dehydrogenase gene. Genomics. 1994 Sep 15;23(2):390–402. doi: 10.1006/geno.1994.1515. [DOI] [PubMed] [Google Scholar]
  7. Comeron J. M., Aguadé M. Synonymous substitutions in the Xdh gene of Drosophila: heterogeneous distribution along the coding region. Genetics. 1996 Nov;144(3):1053–1062. doi: 10.1093/genetics/144.3.1053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Correll C. C., Batie C. J., Ballou D. P., Ludwig M. L. Phthalate dioxygenase reductase: a modular structure for electron transfer from pyridine nucleotides to [2Fe-2S]. Science. 1992 Dec 4;258(5088):1604–1610. doi: 10.1126/science.1280857. [DOI] [PubMed] [Google Scholar]
  9. Critchley D. J., Rance D. J., Beedham C. Subcellular localisation of guinea pig hepatic molybdenum hydroxylases. Biochem Biophys Res Commun. 1992 May 29;185(1):54–59. doi: 10.1016/s0006-291x(05)80954-4. [DOI] [PubMed] [Google Scholar]
  10. Donelli M. G., D'Incalci M., Garattini S. Pharmacokinetic studies of anticancer drugs in tumor-bearing animals. Cancer Treat Rep. 1984 Feb;68(2):381–400. [PubMed] [Google Scholar]
  11. Glatigny A., Scazzocchio C. Cloning and molecular characterization of hxA, the gene coding for the xanthine dehydrogenase (purine hydroxylase I) of Aspergillus nidulans. J Biol Chem. 1995 Feb 24;270(8):3534–3550. doi: 10.1074/jbc.270.8.3534. [DOI] [PubMed] [Google Scholar]
  12. Guyton K. Z., Xu Q., Holbrook N. J. Induction of the mammalian stress response gene GADD153 by oxidative stress: role of AP-1 element. Biochem J. 1996 Mar 1;314(Pt 2):547–554. doi: 10.1042/bj3140547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hille R., Nishino T. Flavoprotein structure and mechanism. 4. Xanthine oxidase and xanthine dehydrogenase. FASEB J. 1995 Aug;9(11):995–1003. [PubMed] [Google Scholar]
  14. Hoff T., Frandsen G. I., Rocher A., Mundy J. Biochemical and genetic characterization of three molybdenum cofactor hydroxylases in Arabidopsis thaliana. Biochim Biophys Acta. 1998 Jul 9;1398(3):397–402. doi: 10.1016/s0167-4781(98)00085-2. [DOI] [PubMed] [Google Scholar]
  15. Holton T. A., Graham M. W. A simple and efficient method for direct cloning of PCR products using ddT-tailed vectors. Nucleic Acids Res. 1991 Mar 11;19(5):1156–1156. doi: 10.1093/nar/19.5.1156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Houde M., Tiveron M. C., Brégégère F. Divergence of the nucleotide sequences encoding xanthine dehydrogenase in Calliphora vicina and Drosophila melanogaster. Gene. 1989 Dec 28;85(2):391–402. doi: 10.1016/0378-1119(89)90432-0. [DOI] [PubMed] [Google Scholar]
  17. Huang D. Y., Ichikawa Y. Two different enzymes are primarily responsible for retinoic acid synthesis in rabbit liver cytosol. Biochem Biophys Res Commun. 1994 Dec 15;205(2):1278–1283. doi: 10.1006/bbrc.1994.2803. [DOI] [PubMed] [Google Scholar]
  18. Jacobs S. A., Stoller R. G., Chabner B. A., Johns D. G. 7-Hydroxymethotrexate as a urinary metabolite in human subjects and rhesus monkeys receiving high dose methotrexate. J Clin Invest. 1976 Feb;57(2):534–538. doi: 10.1172/JCI108308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kozak M. Interpreting cDNA sequences: some insights from studies on translation. Mamm Genome. 1996 Aug;7(8):563–574. doi: 10.1007/s003359900171. [DOI] [PubMed] [Google Scholar]
  20. Krenitsky T. A., Neil S. M., Elion G. B., Hitchings G. H. A comparison of the specificities of xanthine oxidase and aldehyde oxidase. Arch Biochem Biophys. 1972 Jun;150(2):585–599. doi: 10.1016/0003-9861(72)90078-1. [DOI] [PubMed] [Google Scholar]
  21. Kurosaki M., Li Calzi M., Scanziani E., Garattini E., Terao M. Tissue- and cell-specific expression of mouse xanthine oxidoreductase gene in vivo: regulation by bacterial lipopolysaccharide. Biochem J. 1995 Feb 15;306(Pt 1):225–234. doi: 10.1042/bj3060225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kurosaki M., Zanotta S., Li Calzi M., Garattini E., Terao M. Expression of xanthine oxidoreductase in mouse mammary epithelium during pregnancy and lactation: regulation of gene expression by glucocorticoids and prolactin. Biochem J. 1996 Nov 1;319(Pt 3):801–810. doi: 10.1042/bj3190801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lee C. S., Curtis D., McCarron M., Love C., Gray M., Bender W., Chovnick A. Mutations affecting expression of the rosy locus in Drosophila melanogaster. Genetics. 1987 May;116(1):55–66. doi: 10.1093/genetics/116.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nishino T., Nishino T. The nicotinamide adenine dinucleotide-binding site of chicken liver xanthine dehydrogenase. Evidence for alteration of the redox potential of the flavin by NAD binding or modification of the NAD-binding site and isolation of a modified peptide. J Biol Chem. 1989 Apr 5;264(10):5468–5473. [PubMed] [Google Scholar]
  25. Ori N., Eshed Y., Pinto P., Paran I., Zamir D., Fluhr R. TAO1, a representative of the molybdenum cofactor containing hydroxylases from tomato. J Biol Chem. 1997 Jan 10;272(2):1019–1025. doi: 10.1074/jbc.272.2.1019. [DOI] [PubMed] [Google Scholar]
  26. Pastorino J. G., Chen S. T., Tafani M., Snyder J. W., Farber J. L. The overexpression of Bax produces cell death upon induction of the mitochondrial permeability transition. J Biol Chem. 1998 Mar 27;273(13):7770–7775. doi: 10.1074/jbc.273.13.7770. [DOI] [PubMed] [Google Scholar]
  27. Romão M. J., Archer M., Moura I., Moura J. J., LeGall J., Engh R., Schneider M., Hof P., Huber R. Crystal structure of the xanthine oxidase-related aldehyde oxido-reductase from D. gigas. Science. 1995 Nov 17;270(5239):1170–1176. doi: 10.1126/science.270.5239.1170. [DOI] [PubMed] [Google Scholar]
  28. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sato A., Nishino T., Noda K., Amaya Y., Nishino T. The structure of chicken liver xanthine dehydrogenase. cDNA cloning and the domain structure. J Biol Chem. 1995 Feb 10;270(6):2818–2826. doi: 10.1074/jbc.270.6.2818. [DOI] [PubMed] [Google Scholar]
  30. Sekimoto H., Seo M., Dohmae N., Takio K., Kamiya Y., Koshiba T. Cloning and molecular characterization of plant aldehyde oxidase. J Biol Chem. 1997 Jun 13;272(24):15280–15285. doi: 10.1074/jbc.272.24.15280. [DOI] [PubMed] [Google Scholar]
  31. Shaw S., Jayatilleke E. The role of aldehyde oxidase in ethanol-induced hepatic lipid peroxidation in the rat. Biochem J. 1990 Jun 15;268(3):579–583. doi: 10.1042/bj2680579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Taylor S. M., Stubley-Beedham C., Stell J. G. Simultaneous formation of 2- and 4-quinolones from quinolinium cations catalysed by aldehyde oxidase. Biochem J. 1984 May 15;220(1):67–74. doi: 10.1042/bj2200067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Terao M., Cazzaniga G., Ghezzi P., Bianchi M., Falciani F., Perani P., Garattini E. Molecular cloning of a cDNA coding for mouse liver xanthine dehydrogenase. Regulation of its transcript by interferons in vivo. Biochem J. 1992 May 1;283(Pt 3):863–870. doi: 10.1042/bj2830863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Terao M., Kurosaki M., Demontis S., Zanotta S., Garattini E. Isolation and characterization of the human aldehyde oxidase gene: conservation of intron/exon boundaries with the xanthine oxidoreductase gene indicates a common origin. Biochem J. 1998 Jun 1;332(Pt 2):383–393. doi: 10.1042/bj3320383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Terao M., Kurosaki M., Zanotta S., Garattini E. The xanthine oxidoreductase gene: structure and regulation. Biochem Soc Trans. 1997 Aug;25(3):791–796. doi: 10.1042/bst0250791. [DOI] [PubMed] [Google Scholar]
  36. Tso J. Y., Sun X. H., Kao T. H., Reece K. S., Wu R. Isolation and characterization of rat and human glyceraldehyde-3-phosphate dehydrogenase cDNAs: genomic complexity and molecular evolution of the gene. Nucleic Acids Res. 1985 Apr 11;13(7):2485–2502. doi: 10.1093/nar/13.7.2485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Tsukihira T., Fukuyama K., Nakamura M., Katsube Y., Tanaka N., Kakudo M., Wada K., Hase T., Matsubara H. X-ray analysis of a [2Fe-2S] ferrodoxin from Spirulina platensis. Main chain fold and location of side chains at 2.5 A resolution. J Biochem. 1981 Dec;90(6):1763–1773. doi: 10.1093/oxfordjournals.jbchem.a133654. [DOI] [PubMed] [Google Scholar]
  38. Wright R. M., Vaitaitis G. M., Wilson C. M., Repine T. B., Terada L. S., Repine J. E. cDNA cloning, characterization, and tissue-specific expression of human xanthine dehydrogenase/xanthine oxidase. Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10690–10694. doi: 10.1073/pnas.90.22.10690. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Yasukochi Y., Kanda T., Tamura T. Cloning of two Bombyx homologues of the Drosophila rosy gene and their relationship to larval translucent skin colour mutants. Genet Res. 1998 Feb;71(1):11–19. doi: 10.1017/s0016672397003078. [DOI] [PubMed] [Google Scholar]
  40. Yoshihara S., Tatsumi K. Guinea pig liver aldehyde oxidase as a sulfoxide reductase: its purification and characterization. Arch Biochem Biophys. 1985 Oct;242(1):213–224. doi: 10.1016/0003-9861(85)90495-3. [DOI] [PubMed] [Google Scholar]
  41. Yoshihara S., Tatsumi K. Involvement of growth hormone as a regulating factor in sex differences of mouse hepatic aldehyde oxidase. Biochem Pharmacol. 1997 Apr 25;53(8):1099–1105. doi: 10.1016/s0006-2952(97)00088-9. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES