![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 60, Issue 6, 1399-1406, December 2001
,25-Dihydroxy Vitamin D3
Department of Pharmaceutics (K.E.T., T.S., Y.L., H.I.), and
Department of Anesthesiology (E.K.), University of Washington, Seattle,
Washington; and Department of Pharmaceutical Sciences (C.B., K.Y.,
J.T., J.S., E.S.), St. Jude Children's Research Hospital, Memphis,
Tennessee
It was previously shown that CYP3A4 is induced in the human intestinal
Caco-2 cell model by treatment with 1
,25-dihydroxy vitamin
D3 (1,25-D3). We demonstrate the vitamin D
analog, 19-nor-1,25-dihydroxy vitamin D2, is also an
effective inducer of CYP3A4 in Caco-2 cells, but with half the potency
of 1,25-D3. We report that treatment of LS180 cells, a
human intestinal cell line, with 1 to 10 nM 1,25-D3 dose
dependently increased CYP3A4 protein and CYP3A4 mRNA expression.
CYP3A4- and CYP3A23-promoter-Luciferase
reporter constructs transiently transfected into LS180 cells were
transcriptionally activated in a dose-dependent manner by
1,25-D3, whereas mutation of the nuclear hormone receptor
binding motif (ER6) in the CYP3A4 promoter abrogated
1,25-D3 activation of CYP3A4. Although the CYP3A4 ER6 promoter element has been shown to bind the
pregnane X receptor (PXR), this receptor does not mediate
1,25-D3 induction of CYP3A4 because a) PXR is not expressed
in Caco-2 cells; b) PXR mRNA expression is not induced by
1,25-D3 treatment of LS180 cells; and c) the ligand binding
domain of human PXR was not activated by 1,25-D3.
1,25-D3 uses the vitamin D receptor to induce CYP3A4 because a) the vitamin D receptor (VDR)-retinoid X receptor (RXR) heterodimer binds specifically to the CYP3A4 ER6; b)
selective mutation of the CYP3A4 ER6 disrupted the
binding of VDR-RXR; and c) reporter constructs containing only three
copies of the CYP3A4 ER6 linked to a TK-CAT reporter were activated by
1,25-D3 only in cells cotransfected with a human VDR
expression plasmid. These data support the hypothesis that
1,25-D3 and VDR induce expression of intestinal CYP3A by
binding of the activated VDR-RXR heterodimer to the
CYP3A PXR response element and promoting gene transcription.
This article has been cited by other articles:
|
|
 |
|
  J. H. White Vitamin D Signaling, Infectious Diseases, and Regulation of Innate Immunity Infect. Immun., September 1, 2008; 76(9): 3837 - 3843. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Harmsen, A. S. Koster, J. H. Beijnen, J. H. M. Schellens, and I. Meijerman Comparison of Two Immortalized Human Cell Lines to Study Nuclear Receptor-Mediated CYP3A4 Induction Drug Metab. Dispos., June 1, 2008; 36(6): 1166 - 1171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kosuge, A. I. Chuang, S. Uematsu, K. P. Tan, K. Ohashi, B. C.B. Ko, and S. Ito Discovery of Osmosensitive Transcriptional Regulation of Human Cytochrome P450 3As by the Tonicity-Responsive Enhancer Binding Protein (Nuclear Factor of Activated T Cells 5) Mol. Pharmacol., October 1, 2007; 72(4): 826 - 837. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Echchgadda, C. S. Song, T. Oh, M. Ahmed, I. J. De La Cruz, and B. Chatterjee The Xenobiotic-Sensing Nuclear Receptors Pregnane X Receptor, Constitutive Androstane Receptor, and Orphan Nuclear Receptor Hepatocyte Nuclear Factor 4{alpha} in the Regulation of Human Steroid-/Bile Acid-Sulfotransferase Mol. Endocrinol., September 1, 2007; 21(9): 2099 - 2111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kishi, C. Cheng, D. French, D. Pei, S. Das, E. H. Cook, N. Hijiya, C. Rizzari, G. L. Rosner, T. Frudakis, et al. Ancestry and pharmacogenetics of antileukemic drug toxicity Blood, May 15, 2007; 109(10): 4151 - 4157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Matsubara, W. Noracharttiyapot, T. Toriyabe, K. Yoshinari, K. Nagata, and Y. Yamazoe Assessment of Human Pregnane X Receptor Involvement in Pesticide-Mediated Activation of CYP3A4 Gene Drug Metab. Dispos., May 1, 2007; 35(5): 728 - 733. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. L. Urquhart, R. G. Tirona, and R. B. Kim Nuclear Receptors and the Regulation of Drug-Metabolizing Enzymes and Drug Transporters: Implications for Interindividual Variability in Response to Drugs J. Clin. Pharmacol., May 1, 2007; 47(5): 566 - 578. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Wang, A. J. Mendy, G. Dai, H.-R. Luo, L. He, and Y.-J. Y. Wan Retinoids Activate the RXR/SXR-Mediated Pathway and Induce the Endogenous CYP3A4 Activity in Huh7 Human Hepatoma Cells Toxicol. Sci., July 1, 2006; 92(1): 51 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Chen, F. Chen, S. Liu, H. Glaeser, P. A. Dawson, A. F. Hofmann, R. B. Kim, B. L. Shneider, and K. S. Pang Transactivation of Rat Apical Sodium-Dependent Bile Acid Transporter and Increased Bile Acid Transport by 1{alpha},25-Dihydroxyvitamin D3 via the Vitamin D Receptor Mol. Pharmacol., June 1, 2006; 69(6): 1913 - 1923. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Zierold, J. A. Mings, and H. F. Deluca 19nor-1,25-Dihydroxyvitamin D2 Specifically Induces CYP3A9 in Rat Intestine More Strongly than 1,25-Dihydroxyvitamin D3 in Vivo and in Vitro Mol. Pharmacol., May 1, 2006; 69(5): 1740 - 1747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Song, I. Echchgadda, Y.-K. Seo, T. Oh, S. Kim, S.-A Kim, S. Cho, L. Shi, and B. Chatterjee An Essential Role of the CAAT/Enhancer Binding Protein-{alpha} in the Vitamin D-Induced Expression of the Human Steroid/Bile Acid-Sulfotransferase (SULT2A1) Mol. Endocrinol., April 1, 2006; 20(4): 795 - 808. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Xu, T. Hashizume, M. C. Shuhart, C. L. Davis, W. L. Nelson, T. Sakaki, T. F. Kalhorn, P. B. Watkins, E. G. Schuetz, and K. E. Thummel Intestinal and Hepatic CYP3A4 Catalyze Hydroxylation of 1{alpha},25-Dihydroxyvitamin D3: Implications for Drug-Induced Osteomalacia Mol. Pharmacol., January 1, 2006; 69(1): 56 - 65. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-T. Wang, L. E. Tavera-Mendoza, D. Laperriere, E. Libby, N. Burton MacLeod, Y. Nagai, V. Bourdeau, A. Konstorum, B. Lallemant, R. Zhang, et al. Large-Scale in Silico and Microarray-Based Identification of Direct 1,25-Dihydroxyvitamin D3 Target Genes Mol. Endocrinol., November 1, 2005; 19(11): 2685 - 2695. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Mathias, J. Hitti, and J. D. Unadkat P-glycoprotein and breast cancer resistance protein expression in human placentae of various gestational ages Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2005; 289(4): R963 - R969. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Mu, C. R. J. Stephenson, C. Kendall, S. P. S. Saini, D. Toma, S. Ren, H. Cai, S. C. Strom, B. W. Day, P. Wipf, et al. A Pregnane X Receptor Agonist with Unique Species-Dependent Stereoselectivity and Its Implications in Drug Development Mol. Pharmacol., August 1, 2005; 68(2): 403 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. C. McCarthy, X. Li, and C. J. Sinal Vitamin D Receptor-dependent Regulation of Colon Multidrug Resistance-associated Protein 3 Gene Expression by Bile Acids J. Biol. Chem., June 17, 2005; 280(24): 23232 - 23242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. C. Rocha, C. Cheng, W. Liu, S. Kishi, S. Das, E. H. Cook, J. T. Sandlund, J. Rubnitz, R. Ribeiro, D. Campana, et al. Pharmacogenetics of outcome in children with acute lymphoblastic leukemia Blood, June 15, 2005; 105(12): 4752 - 4758. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Tian, N. Koyabu, S. Morimoto, Y. Shoyama, H. Ohtani, and Y. Sawada FUNCTIONAL INDUCTION AND DE-INDUCTION OF P-GLYCOPROTEIN BY ST. JOHN'S WORT AND ITS INGREDIENTS IN A HUMAN COLON ADENOCARCINOMA CELL LINE Drug Metab. Dispos., April 1, 2005; 33(4): 547 - 554. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Adachi, Y. Honma, H. Masuno, K. Kawana, I. Shimomura, S. Yamada, and M. Makishima Selective activation of vitamin D receptor by lithocholic acid acetate, a bile acid derivative J. Lipid Res., January 1, 2005; 46(1): 46 - 57. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. V. Relling, W. Yang, S. Das, E. H. Cook, G. L. Rosner, M. Neel, S. Howard, R. Ribeiro, J. T. Sandlund, C.-H. Pui, et al. Pharmacogenetic Risk Factors for Osteonecrosis of the Hip Among Children With Leukemia J. Clin. Oncol., October 1, 2004; 22(19): 3930 - 3936. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Bi and P. K. Rogan Bipartite pattern discovery by entropy minimization-based multiple local alignment Nucleic Acids Res., September 23, 2004; 32(17): 4979 - 4991. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Mitin, L. L. von Moltke, M. H. Court, and D. J. Greenblatt LEVOTHYROXINE UP-REGULATES P-GLYCOPROTEIN INDEPENDENT OF THE PREGNANE X RECEPTOR Drug Metab. Dispos., August 1, 2004; 32(8): 779 - 782. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yasunami, H. Hara, T. Iwamura, T. Kataoka, and T. Adachi C-JUN N-TERMINAL KINASE MODULATES 1,25-DIHYDROXYVITAMIN D3-INDUCED CYTOCHROME P450 3A4 GENE EXPRESSION Drug Metab. Dispos., July 1, 2004; 32(7): 685 - 688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Echchgadda, C. S. Song, A. K. Roy, and B. Chatterjee Dehydroepiandrosterone Sulfotransferase Is a Target for Transcriptional Induction by the Vitamin D Receptor Mol. Pharmacol., March 1, 2004; 65(3): 720 - 729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kishi, W. Yang, B. Boureau, S. Morand, S. Das, P. Chen, E. H. Cook, G. L. Rosner, E. Schuetz, C.-H. Pui, et al. Effects of prednisone and genetic polymorphisms on etoposide disposition in children with acute lymphoblastic leukemia Blood, January 1, 2004; 103(1): 67 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. S. Pang MODELING OF INTESTINAL DRUG ABSORPTION: ROLES OF TRANSPORTERS AND METABOLIC ENZYMES (FOR THE GILLETTE REVIEW SERIES) Drug Metab. Dispos., December 1, 2003; 31(12): 1507 - 1519. [Full Text] [PDF]
|
|
|
|
 |
|
 C. Handschin and U. A. Meyer Induction of Drug Metabolism: The Role of Nuclear Receptors Pharmacol. Rev., December 1, 2003; 55(4): 649 - 673. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Tam, H. Sun, and K. S. Pang INFLUENCE OF P-GLYCOPROTEIN, TRANSFER CLEARANCES, AND DRUG BINDING ON INTESTINAL METABOLISM IN CACO-2 CELL MONOLAYERS OR MEMBRANE PREPARATIONS: A THEORETICAL ANALYSIS Drug Metab. Dispos., October 1, 2003; 31(10): 1214 - 1226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. K. Whitfield, H. T. L. Dang, S. F. Schluter, R. M. Bernstein, T. Bunag, L. A. Manzon, G. Hsieh, C. Encinas Dominguez, J. H. Youson, M. R. Haussler, et al. Cloning of a Functional Vitamin D Receptor from the Lamprey (Petromyzon marinus), an Ancient Vertebrate Lacking a Calcified Skeleton and Teeth Endocrinology, June 1, 2003; 144(6): 2704 - 2716. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Theodoropoulos, C. Demers, J.-L. Petit, and M. Gascon-Barre High sensitivity of rat hepatic vitamin D3-25 hydroxylase CYP27A to 1,25-dihydroxyvitamin D3 administration Am J Physiol Endocrinol Metab, January 1, 2003; 284(1): E138 - E147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Sonoda, W. Xie, J. M. Rosenfeld, J. L. Barwick, P. S. Guzelian, and R. M. Evans Regulation of a xenobiotic sulfonation cascade by nuclear pregnane X receptor (PXR) PNAS, October 15, 2002; 99(21): 13801 - 13806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Drocourt, J.-C. Ourlin, J.-M. Pascussi, P. Maurel, and M.-J. Vilarem Expression of CYP3A4, CYP2B6, and CYP2C9 Is Regulated by the Vitamin D Receptor Pathway in Primary Human Hepatocytes J. Biol. Chem., July 5, 2002; 277(28): 25125 - 25132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Burk, H. Tegude, I. Koch, E. Hustert, R. Wolbold, H. Glaeser, K. Klein, M. F. Fromm, A. K. Nuessler, P. Neuhaus, et al. Molecular Mechanisms of Polymorphic CYP3A7 Expression in Adult Human Liver and Intestine J. Biol. Chem., June 28, 2002; 277(27): 24280 - 24288. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Makishima, T. T. Lu, W. Xie, G. K. Whitfield, H. Domoto, R. M. Evans, M. R. Haussler, and D. J. Mangelsdorf Vitamin D Receptor As an Intestinal Bile Acid Sensor Science, May 17, 2002; 296(5571): 1313 - 1316. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
