Abstract
In the mammary gland of virgin mice, xanthine oxidoreductase (XOR) enzymic activity is barely measurable. a high increase in the levels of the enzyme is observed during the last days of pregnancy and during lactation, and this is parallelled by an elevation in the amounts of the respective protein and transcript. In situ hybridization experiments demonstrate that the XOR mRNA is specifically expressed in the alveolar epithelial cells of the mammary gland. In HC11 cells, a model culture system for normal breast epithelium, the levels of XOR enzymic activity are dose- and time-dependently induced by dexamethasone, and a further synergistic augmentation is observed in the presence of dexamethasone plus prolactin. Increased XOR gene expression is consequent on glucocorticoid receptor activation, as indicated by sensitivity to the specific receptor antagonist RU486. In addition, the phenomenon is likely to involve protein phosphorylation and dephosphorylation events, as suggested by modulation of XOR mRNA by tyrosine kinase and phosphatase inhibitors.
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- Abadeh S., Killacky J., Benboubetra M., Harrison R. Purification and partial characterization of xanthine oxidase from human milk. Biochim Biophys Acta. 1992 Jul 21;1117(1):25–32. doi: 10.1016/0304-4165(92)90157-p. [DOI] [PubMed] [Google Scholar]
- Akaike T., Ando M., Oda T., Doi T., Ijiri S., Araki S., Maeda H. Dependence on O2- generation by xanthine oxidase of pathogenesis of influenza virus infection in mice. J Clin Invest. 1990 Mar;85(3):739–745. doi: 10.1172/JCI114499. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Ball R. K., Friis R. R., Schoenenberger C. A., Doppler W., Groner B. Prolactin regulation of beta-casein gene expression and of a cytosolic 120-kd protein in a cloned mouse mammary epithelial cell line. EMBO J. 1988 Jul;7(7):2089–2095. doi: 10.1002/j.1460-2075.1988.tb03048.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Beedham C. Molybdenum hydroxylases as drug-metabolizing enzymes. Drug Metab Rev. 1985;16(1-2):119–156. doi: 10.3109/03602538508991432. [DOI] [PubMed] [Google Scholar]
- Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
- Carpani G., Racchi M., Ghezzi P., Terao M., Garattini E. Purification and characterization of mouse liver xanthine oxidase. Arch Biochem Biophys. 1990 Jun;279(2):237–241. doi: 10.1016/0003-9861(90)90487-j. [DOI] [PubMed] [Google Scholar]
- 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]
- Corte E. D., Stirpe F. The regulation of rat liver xanthine oxidase. Involvement of thiol groups in the conversion of the enzyme activity from dehydrogenase (type D) into oxidase (type O) and purification of the enzyme. Biochem J. 1972 Feb;126(3):739–745. doi: 10.1042/bj1260739. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DaSilva L., Howard O. M., Rui H., Kirken R. A., Farrar W. L. Growth signaling and JAK2 association mediated by membrane-proximal cytoplasmic regions of prolactin receptors. J Biol Chem. 1994 Jul 15;269(28):18267–18270. [PubMed] [Google Scholar]
- Darnell J. E., Jr, Kerr I. M., Stark G. R. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science. 1994 Jun 3;264(5164):1415–1421. doi: 10.1126/science.8197455. [DOI] [PubMed] [Google Scholar]
- David M., Petricoin E. F., 3rd, Igarashi K., Feldman G. M., Finbloom D. S., Larner A. C. Prolactin activates the interferon-regulated p91 transcription factor and the Jak2 kinase by tyrosine phosphorylation. Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7174–7178. doi: 10.1073/pnas.91.15.7174. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Doppler W., Groner B., Ball R. K. Prolactin and glucocorticoid hormones synergistically induce expression of transfected rat beta-casein gene promoter constructs in a mammary epithelial cell line. Proc Natl Acad Sci U S A. 1989 Jan;86(1):104–108. doi: 10.1073/pnas.86.1.104. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dupont G. P., Huecksteadt T. P., Marshall B. C., Ryan U. S., Michael J. R., Hoidal J. R. Regulation of xanthine dehydrogenase and xanthine oxidase activity and gene expression in cultured rat pulmonary endothelial cells. J Clin Invest. 1992 Jan;89(1):197–202. doi: 10.1172/JCI115563. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dusanter-Fourt I., Muller O., Ziemiecki A., Mayeux P., Drucker B., Djiane J., Wilks A., Harpur A. G., Fischer S., Gisselbrecht S. Identification of JAK protein tyrosine kinases as signaling molecules for prolactin. Functional analysis of prolactin receptor and prolactin-erythropoietin receptor chimera expressed in lymphoid cells. EMBO J. 1994 Jun 1;13(11):2583–2591. doi: 10.1002/j.1460-2075.1994.tb06548.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Falciani F., Ghezzi P., Terao M., Cazzaniga G., Garattini E. Interferons induce xanthine dehydrogenase gene expression in L929 cells. Biochem J. 1992 Aug 1;285(Pt 3):1001–1008. doi: 10.1042/bj2851001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Falciani F., Terao M., Goldwurm S., Ronchi A., Gatti A., Minoia C., Li Calzi M., Salmona M., Cazzaniga G., Garattini E. Molybdenum(VI) salts convert the xanthine oxidoreductase apoprotein into the active enzyme in mouse L929 fibroblastic cells. Biochem J. 1994 Feb 15;298(Pt 1):69–77. doi: 10.1042/bj2980069. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Garrett R. M., Rajagopalan K. V. Molecular cloning of rat liver sulfite oxidase. Expression of a eukaryotic Mo-pterin-containing enzyme in Escherichia coli. J Biol Chem. 1994 Jan 7;269(1):272–276. [PubMed] [Google Scholar]
- Gouilleux F., Wakao H., Mundt M., Groner B. Prolactin induces phosphorylation of Tyr694 of Stat5 (MGF), a prerequisite for DNA binding and induction of transcription. EMBO J. 1994 Sep 15;13(18):4361–4369. doi: 10.1002/j.1460-2075.1994.tb06756.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Hayden T. J., Brennan D., Quirke K., Murphy P. Xanthine oxidase/dehydrogenase in mammary gland of mouse: relationship to mammogenesis and lactogenesis in vivo and in vitro. J Dairy Res. 1991 Nov;58(4):401–409. doi: 10.1017/s0022029900030004. [DOI] [PubMed] [Google Scholar]
- Hunt J., Massey V. Purification and properties of milk xanthine dehydrogenase. J Biol Chem. 1992 Oct 25;267(30):21479–21485. [PubMed] [Google Scholar]
- Jarasch E. D., Grund C., Bruder G., Heid H. W., Keenan T. W., Franke W. W. Localization of xanthine oxidase in mammary-gland epithelium and capillary endothelium. Cell. 1981 Jul;25(1):67–82. doi: 10.1016/0092-8674(81)90232-4. [DOI] [PubMed] [Google Scholar]
- Kooij A., Frederiks W. M., Gossrau R., Van Noorden C. J. Localization of xanthine oxidoreductase activity using the tissue protectant polyvinyl alcohol and final electron acceptor Tetranitro BT. J Histochem Cytochem. 1991 Jan;39(1):87–93. doi: 10.1177/39.1.1983876. [DOI] [PubMed] [Google Scholar]
- Kramer S. P., Johnson J. L., Ribeiro A. A., Millington D. S., Rajagopalan K. V. The structure of the molybdenum cofactor. Characterization of di-(carboxamidomethyl)molybdopterin from sulfite oxidase and xanthine oxidase. J Biol Chem. 1987 Dec 5;262(34):16357–16363. [PubMed] [Google Scholar]
- 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]
- Li M. L., Aggeler J., Farson D. A., Hatier C., Hassell J., Bissell M. J. Influence of a reconstituted basement membrane and its components on casein gene expression and secretion in mouse mammary epithelial cells. Proc Natl Acad Sci U S A. 1987 Jan;84(1):136–140. doi: 10.1073/pnas.84.1.136. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lin C. Q., Bissell M. J. Multi-faceted regulation of cell differentiation by extracellular matrix. FASEB J. 1993 Jun;7(9):737–743. doi: 10.1096/fasebj.7.9.8330681. [DOI] [PubMed] [Google Scholar]
- Massey V., Brumby P. E., Komai H. Studies on milk xanthine oxidase. Some spectral and kinetic properties. J Biol Chem. 1969 Apr 10;244(7):1682–1691. [PubMed] [Google Scholar]
- Nishino T. The conversion of xanthine dehydrogenase to xanthine oxidase and the role of the enzyme in reperfusion injury. J Biochem. 1994 Jul;116(1):1–6. doi: 10.1093/oxfordjournals.jbchem.a124480. [DOI] [PubMed] [Google Scholar]
- Parks D. A., Granger D. N. Ischemia-induced vascular changes: role of xanthine oxidase and hydroxyl radicals. Am J Physiol. 1983 Aug;245(2):G285–G289. doi: 10.1152/ajpgi.1983.245.2.G285. [DOI] [PubMed] [Google Scholar]
- Peden D. B., Hohman R., Brown M. E., Mason R. T., Berkebile C., Fales H. M., Kaliner M. A. Uric acid is a major antioxidant in human nasal airway secretions. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7638–7642. doi: 10.1073/pnas.87.19.7638. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Persico M. G., Viglietto G., Martini G., Toniolo D., Paonessa G., Moscatelli C., Dono R., Vulliamy T., Luzzatto L., D'Urso M. Isolation of human glucose-6-phosphate dehydrogenase (G6PD) cDNA clones: primary structure of the protein and unusual 5' non-coding region. Nucleic Acids Res. 1986 Mar 25;14(6):2511–2522. doi: 10.1093/nar/14.6.2511. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seiler-Tuyns A., Birnstiel M. L. Structure and expression in L-cells of a cloned H4 histone gene of the mouse. J Mol Biol. 1981 Oct 5;151(4):607–625. doi: 10.1016/0022-2836(81)90426-5. [DOI] [PubMed] [Google Scholar]
- Suzuki M., Grisham M. B., Granger D. N. Leukocyte-endothelial cell adhesive interactions: role of xanthine oxidase-derived oxidants. J Leukoc Biol. 1991 Nov;50(5):488–494. doi: 10.1002/jlb.50.5.488. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Ventom A. M., Deistung J., Bray R. C. The isolation of demolybdo xanthine oxidase from bovine milk. Biochem J. 1988 Nov 1;255(3):949–956. doi: 10.1042/bj2550949. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wakao H., Gouilleux F., Groner B. Mammary gland factor (MGF) is a novel member of the cytokine regulated transcription factor gene family and confers the prolactin response. EMBO J. 1994 May 1;13(9):2182–2191. doi: 10.1002/j.1460-2075.1994.tb06495.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yoshimura M., Oka T. Isolation and structural analysis of the mouse beta-casein gene. Gene. 1989 May 30;78(2):267–275. doi: 10.1016/0378-1119(89)90229-1. [DOI] [PubMed] [Google Scholar]