Modulation of ABC Transporters by Nuclear Receptors: Physiological, Pathological and Pharmacological Aspects

Author(s): Juan Pablo Rigalli , Guillermo Nicolás Tocchetti , Johanna Weiss* .

Journal Name: Current Medicinal Chemistry

Volume 26 , Issue 7 , 2019

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Abstract:

ABC transporters are membrane proteins mediating the efflux of endo- and xenobiotics. Transporter expression is not static but instead is subject to a dynamic modulation aiming at responding to changes in the internal environment and thus at maintaining homeostatic conditions. Nuclear receptors are ligand modulated transcription factors that get activated upon changes in the intracellular concentrations of the respective agonists and bind to response elements within the promoter of ABC transporters, thus modulating their expression and, consequently, their activity. This review compiles information about transporter regulation by nuclear receptors classified according to the perpetrator compounds and the biological effects resulting from the regulation. Modulation by hormone receptors is involved in maintaining endocrine homeostasis and may also lead to an altered efflux of other substrates in cases of altered hormonal levels. Xenobiotic receptors play a key role in limiting the accumulation of potentially harmful compounds. In addition, their frequent activation by therapeutic agents makes them common molecular elements mediating drug-drug interactions and cancer multidrug resistance. Finally, lipid and retinoid receptors are usually activated by endogenous molecules, thus sensing metabolic changes and inducing ABC transporters to counteract potential alterations. Furthermore, the axis nuclear receptor-ABC transporter constitutes a promising therapeutic target for the treatment of several disease states like cancer, atherosclerosis and dyslipidemia. In the current work, we summarize the information available on the pharmacological potential of nuclear receptor modulators and discuss their applicability in the clinical practice.

Keywords: ABC transporters, drug transporters, nuclear receptors, drug-drug interactions, hormone receptors, Pglycoprotein, multidrug resistance-associated proteins, pregnane x receptor.

[1]
Nuclear Receptors Nomenclature Committee. A Unified Nomenclature System for the Nuclear Receptor Superfamily. Cell, 1999, 97(100), 161-163.
[2]
Chen, Y.; Tang, Y.; Guo, C.; Wang, J.; Boral, D.; Nie, D. Nuclear receptors in the multidrug resistance through the regulation of drug-metabolizing enzymes and drug transporters. Biochem. Pharmacol., 2012, 83(8), 1112-1126.
[3]
Germain, P.; Staels, B.; Dacquet, C.; Spedding, M.; Laudet, V. Overview of nomenclature of nuclear receptors. Pharmacol. Rev., 2006, 58(4), 685-704.
[4]
Fowler, A.M.; Solodin, N.; Preisler-Mashek, M.T.; Zhang, P.; Lee, A.V.; Alarid, E.T. Increases in estrogen receptor-alpha concentration in breast cancer cells promote serine 118/104/106-independent AF-1 transactivation and growth in the absence of estrogen. FASEB J., 2004, 18(1), 81-93.
[5]
Matthews, L.; Johnson, J.; Berry, A.; Trebble, P.; Cookson, A.; Spiller, D.; Rivers, C.; Norman, M.; White, M.; Ray, D. Cell cycle phase regulates glucocorticoid receptor function. PLoS One, 2011, 6(7), e22289.
[6]
Mavinakere, M.S.; Powers, J.M.; Subramanian, K.S.; Roggero, V.R.; Allison, L.A. Multiple Novel Signals Mediate Thyroid Hormone Receptor Nuclear Import and Export. J. Biol. Chem., 2012, 287(37), 31280-31297.
[7]
Necela, B.M.; Cidlowski, J.A. A single amino acid change in the first zinc finger of the DNA binding domain of the glucocorticoid receptor regulates differential promoter selectivity. J. Biol. Chem., 2004, 279(38), 39279-39288.
[8]
Jones, S.A.; Moore, L.B.; Shenk, J.L.; Wisely, G.B.; Hamilton, G.A.; McKee, D.D.; Tomkinson, N.C.; LeCluyse, E.L.; Lambert, M.H.; Willson, T.M.; Kliewer, S.A.; Moore, J.T. The pregnane X receptor: a promiscuous xenobiotic receptor that has diverged during evolution. Mol. Endocrinol., 2000, 14(1), 27-39.
[9]
Yang, J.; Singleton, D.W.; Shaughnessy, E.A.; Khan, S.A. The F-domain of estrogen receptor-alpha inhibits ligand induced receptor dimerization. Mol. Cell. Endocrinol., 2008, 295(1-2), 94-100.
[10]
Billas, I.; Moras, D. Allosteric controls of nuclear receptor function in the regulation of transcription. J. Mol. Biol., 2013, 425(13), 2317-2329.
[11]
Dasgupta, S.; Lonard, D.M.; O’Malley, B.W. Nuclear receptor coactivators: master regulators of human health and disease. Annu. Rev. Med., 2014, 65(3), 279-292.
[12]
Johnson, D.R.; Li, C-W.; Chen, L-Y.; Ghosh, J.C.; Chen, J.D. Regulation and binding of pregnane X receptor by nuclear receptor corepressor silencing mediator of retinoid and thyroid hormone receptors (SMRT). Mol. Pharmacol., 2006, 69(1), 99-108.
[13]
Leonhardt, S.A.; Boonyaratanakornkit, V.; Edwards, D.P. Progesterone receptor transcription and non-transcription signaling mechanisms. Steroids, 2003, 68(10-13), 761-770.
[14]
Marino, M.; Galluzzo, P.; Ascenzi, P. Estrogen signaling multiple pathways to impact gene transcription. Curr. Genomics, 2006, 7(8), 497-508.
[15]
Hodgson, M.C.; Shen, H.C.; Hollenberg, A.N.; Balk, S.P. Structural basis for nuclear receptor corepressor recruitment by antagonist-liganded androgen receptor. Mol. Cancer Ther., 2008, 7(10), 3187-3194.
[16]
Huq, M.D.M.; Gupta, P.; Tsai, N-P.; Wei, L-N. Modulation of testicular receptor 4 activity by mitogen-activated protein kinase-mediated phosphorylation. Mol. Cell. Proteomics, 2006, 5(11), 2072-2082.
[17]
Mani, S.; Huang, H.; Sundarababu, S.; Liu, W.; Kalpana, G.; Smith, A.B.; Horwitz, S.B. Activation of the steroid and xenobiotic receptor (human pregnane X receptor) by nontaxane microtubule-stabilizing agents. Clin. Cancer Res., 2005, 11(17), 6359-6369.
[18]
Thyroid Disorders. Basic Science and Clinical Practice., Imam, S. K., Ahmad, S. I., Eds.; Springer International Publishing. 2016.
[19]
Kurose, K.; Saeki, M.; Tohkin, M.; Hasegawa, R. Thyroid hormone receptor mediates human MDR1 gene expression-Identification of the response region essential for gene expression. Arch. Biochem. Biophys., 2008, 474(1), 82-90.
[20]
Çetinkalp, S.; Karadeniz, M.; Erdoğan, M.; Eroğlu, Z.; Zengi, A.; Kosova, B.; Yilmaz, C.; Tezcanli, B.; Kabalak, T.; Özgen, A. Human Multidrug Resistance-1 Gene Expression Levels in Graves-Basedow Disease. Exp. Clin. Endocrinol. Diabetes, 2010, 118, 158-160.
[21]
Burk, O.; Brenner, S.S.; Hofmann, U.; Tegude, H.; Igel, S.; Schwab, M.; Eichelbaum, M.; Alscher, M.D. The impact of thyroid disease on the regulation, expression, and function of ABCB1 (MDR1/P glycoprotein) and consequences for the disposition of digoxin. Clin. Pharmacol. Ther., 2010, 88(5), 685-694.
[22]
Astapova, I.; Ramadoss, P. Costa-E-Sousa, R. H.; Ye, F.; Holtz, K. A.; Li, Y.; Niepel, M. W.; Cohen, D. E.; Hollenberg, A. N. Hepatic nuclear corepressor 1 regulates cholesterol absorption through a TRβ1-governed pathway. J. Clin. Invest., 2014, 124(5), 1976-1986.
[23]
Saeki, M.; Kurose, K.; Tohkin, M.; Hasegawa, R. Identification of the functional vitamin D response elements in the human MDR1 gene. Biochem. Pharmacol., 2008, 76(4), 531-542.
[24]
Tachibana, S.; Yoshinari, K.; Chikada, T.; Toriyabe, T.; Nagata, K.; Yamazoe, Y. Involvement of Vitamin D Receptor in the Intestinal Induction of Human ABCB1. Drug Metab. Dispos., 2009, 37(8), 1604-1610.
[25]
Fan, J.; Liu, S.; Du, Y.; Morrison, J.; Shipman, R.; Pang, K.S. Up-Regulation of Transporters and Enzymes by the Vitamin D Receptor Ligands, 1alpha, 25-Dihydroxyvitamin D3 and Vitamin D Analogs, in the Caco-2 Cell Monolayer. J. Pharmacol. Exp. Ther., 2009, 330(2), 389-402.
[26]
Durk, M.R.; Chan, G.N.Y.; Campos, C.R.; Peart, J.C.; Chow, E.C.Y.; Lee, E.; Cannon, R.E.; Bendayan, R.; Miller, D.S.; Pang, K.S. 1α,25-Dihydroxyvitamin D3-liganded vitamin D receptor increases expression and transport activity of P-glycoprotein in isolated rat brain capillaries and human and rat brain microvessel endothelial cells. J. Neurochem., 2012, 123(6), 944-953.
[27]
Chow, E.C.Y.; Durk, M.R.; Cummins, C.L.; Pang, K.S. 1α,25-Dihydroxyvitamin D3 up-regulates P-glycoprotein via the vitamin D receptor and not farnesoid X receptor in both fxr (-/-) and fxr (+/+) mice and increased renal and brain efflux of digoxin in mice in vivo. J. Pharmacol. Exp. Ther., 2011, 337(3), 846-859.
[28]
Maeng, H.; Durk, M.; Chow, E.C.Y.; Ghoneim, R.; Pang, K.S. 1α,25-Dihydroxyvitamin D3 on intestinal transporter function: Studies with the rat everted intestinal sac. Biopharm. Drug Dispos., 2011, 32(3), 112-125.
[29]
Arias, A.; Rigalli, J.P.; Villanueva, S.S.M.; Ruiz, M.L.; Luquita, M.G.; Perdomo, V.G.; Vore, M.; Catania, V.A.; Mottino, A.D. Regulation of expression and activity of multidrug resistance proteins MRP2 and MDR1 by estrogenic compounds in Caco-2 cells. Role in prevention of xenobiotic-induced cytotoxicity. Toxicology, 2014, 320(1), 46-55.
[30]
Xiao, C.Q.; Chen, R.; Lin, J.; Wang, G.; Chen, Y.; Tan, Z.R.; Zhou, H.H. Effect of genistein on the activities of cytochrome P450 3A and P-glycoprotein in Chinese healthy participants. Xenobiotica, 2012, 42(2), 173-178.
[31]
Zuloaga, K.L.; Swift, S.N.; Gonzales, R.J.; Wu, T.J.; Handa, R.J. The androgen metabolite, 5α-androstane-3β,17β-diol, decreases cytokine-induced cyclooxygenase-2, vascular cell adhesion molecule-1 expression, and P-glycoprotein expression in male human brain microvascular endothelial cells. Endocrinology, 2012, 153(12), 5949-5960.
[32]
Mahringer, A.; Fricker, G. BCRP at the Blood - Brain Barrier: Genomic Regulation by 17-Estradiol. Mol. Pharm., 2010, 7(5), 1835-1847.
[33]
Nickel, S.; Mahringer, A. The xenoestrogens ethinylestradiol and bisphenol A regulate BCRP at the blood-brain barrier of rats. Xenobiotica, 2014, 8254(11), 1-9.
[34]
Hartz, A.M.S.; Madole, E.K.; Miller, D.S.; Bauer, B. Estrogen Receptor β Signaling through Phosphatase and Tensin Homolog/Phosphoinositide 3-Kinase/Akt/Glycogen Synthase Kinase 3 Down-Regulates Blood-Brain Barrier Breast Cancer Resistance Protein. J. Pharmacol. Exp. Ther., 2010, 334(2), 467-476.
[35]
Koraïchi, F.; Inoubli, L.; Lakhdari, N.; Meunier, L.; Vega, A.; Mauduit, C.; Benahmed, M.; Prouillac, C.; Lecoeur, S. Neonatal exposure to zearalenone induces long term modulation of ABC transporter expression in testis. Toxicology, 2013, 310, 29-38.
[36]
Vähäkangas, K.; Myllynen, P. Drug transporters in the human blood-placental barrier. Br. J. Pharmacol., 2009, 158(3), 665-678.
[37]
Wang, H.; Zhou, L.; Gupta, A.; Vethanayagam, R.R.; Zhang, Y.; Unadkat, J.D.; Mao, Q. Regulation of BCRP/ABCG2 expression by progesterone and 17beta-estradiol in human placental BeWo cells. Am. J. Physiol. Endocrinol. Metab., 2006, 290, E798-E807.
[38]
Yasuda, S.; Kobayashi, M.; Itagaki, S.; Hirano, T.; Iseki, K. Response of the ABCG2 promoter in T47D cells and BeWo cells to sex hormone treatment. Mol. Biol. Rep., 2009, 36(7), 1889-1896.
[39]
Sieppi, E.; Vähäkangas, K.; Rautio, A.; Ietta, F.; Paulesu, L.; Myllynen, P. The xenoestrogens, bisphenol A and para-nonylphenol, decrease the expression of the ABCG2 transporter protein in human term placental explant cultures. Mol. Cell. Endocrinol., 2016, 429, 41-49.
[40]
Ruiz, M.L.; Rigalli, J.P.; Arias, A.; Villanueva, S.S.M.; Banchio, C.; Vore, M.; Mottino, A.D.; Catania, V.A. induction of hepatic multidrug resistance-associated protein 3 by ethynylestradiol is independent of cholestasis and mediated by estrogen receptor. Drug Metab. Dispos., 2013, 41(2), 275-280.
[41]
Ruiz, M.L.; Rigalli, J.P.; Arias, A.; Villanueva, S.S.M.; Banchio, C.; Vore, M.; Mottino, A.D.; Catania, V.A. Estrogen receptor-a mediates human multidrug resistance associated protein 3 induction by 17a-ethynylestradiol. Role of activator protein-1. Biochem. Pharmacol., 2013, 86(3), 401-409.
[42]
Miners, J.; Attwood, J.; Birkett, D. Influence of sex and oral contraceptive steroids on Paracetamol metabolism. Br. J. Clin. Pharmacol., 1983, 16, 503-509.
[43]
Song, X.; Vasilenko, A.; Chen, Y.; Valanejad, L.; Verma, R.; Yan, B.; Deng, R. Transcriptional dynamics of bile salt export pump during pregnancy: Mechanisms and implications in intrahepatic cholestasis of pregnancy. Hepatology, 2014, 60(6), 1993-2007.
[44]
Chen, Y.; Vasilenko, A.; Song, X.; Valanejad, L.; Verma, R.; You, S.; Yan, B.; Shiffka, S.; Hargreaves, L.; Nadolny, C.; Deng, R. Estrogen and estrogen receptor-α-mediated transrepression of bile salt export pump. Mol. Endocrinol., 2015, 29(4), 6.
[45]
Yamamoto, Y.; Moore, R.; Hess, H.A.; Guo, G.L.; Gonzalez, F.J.; Korach, K.S.; Maronpot, R.R.; Negishi, M. Estrogen receptor α mediates 17α-ethynylestradiol causing hepatotoxicity. J. Biol. Chem., 2006, 281(24), 16625-16631.
[46]
Shi, J.F.; Yang, N.; Ding, H.J.; Zhang, J.X.; Hu, M.L.; Leng, Y.; Han, X.; Sun, Y.J. ERα directly activated the MDR1 transcription to increase paclitaxel-resistance of ERα-positive breast cancer cells in vitro and in vivo. Int. J. Biochem. Cell Biol., 2014, 53, 35-45.
[47]
Honorat, M.; Mesnier, A.; Vendrell, J.; Guitton, J.; Bieche, I.; Lidereau, R.; Kruh, G.D.; Dumontet, C.; Cohen, P.; Payen, L. ABCC11 expression is regulated by estrogen in MCF7 cells, correlated with estrogen receptor α expression in postmenopausal breast tumors and overexpressed in tamoxifen-resistant breast cancer cells. Endocr. Relat. Cancer, 2008, 15(1), 125-138.
[48]
Ma, X.J.; Wang, Z.; Ryan, P.D.; Isakoff, S.J.; Barmettler, A.; Fuller, A.; Muir, B.; Mohapatra, G.; Salunga, R.; Tuggle, J.T.; Tran, Y.; Tran, D.; Tassin, A.; Amon, P.; Wang, W.; Wang, W.; Enright, E.; Stecker, K.; Estepa-Sabal, E.; Smith, B.; Younger, J.; Balis, U.; Michaelson, J.; Bhan, A.; Habin, K.; Baer, T.M.; Brugge, J.; Haber, D.A.; Erlander, M.G.; Sgroi, D.C. A two-gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen. Cancer Cell, 2004, 5(6), 607-616.
[49]
Zhang, Y.; Zhou, G.; Wang, H.; Zhang, X.; Wei, F.; Cai, Y.; Yin, D. Transcriptional upregulation of breast cancer resistance protein by 17beta-estradiol in ERalpha-positive MCF-7 breast cancer cells. Oncology, 2006, 71(5-6), 446-455.
[50]
Zhang, Y.; Wang, H.; Wei, L.; Li, G.; Yu, J.; Gao, Y.; Gao, P.; Zhang, X.; Wei, F.; Yin, D.; Zhou, G. Transcriptional modulation of BCRP gene to reverse multidrug resistance by toremifene in breast adenocarcinoma cells. Breast Cancer Res. Treat., 2010, 123(3), 679-689.
[51]
Pradhan, M.; Bembinster, L.A.; Baumgarten, S.C.; Frasor, J. Proinflammatory cytokines enhance estrogen-dependent expression of the multidrug transporter gene ABCG2 through estrogen receptor and NFκB cooperativity at adjacent response elements. J. Biol. Chem., 2010, 285(41), 31100-31106.
[52]
Li, W.; Jia, M.; Qin, X.; Hu, J.; Zhang, X.; Zhou, G. Harmful effect of ERβ on BCRP-mediated drug resistance and cell proliferation in ERα/PR-negative breast cancer. FEBS J., 2013, 280(23), 6128-6140.
[53]
Imai, Y.; Ishikawa, E.; Asada, S.; Sugimoto, Y. Estrogen-Mediated Post transcriptional Down-regulation of Breast Cancer Resistance Protein/ABCG2. Cancer Res., 2005, 65(2), 1-5.
[54]
Kauffmann, H.M.; Pfannschmidt, S.; Zöller, H.; Benz, A.; Vorderstemann, B.; Webster, J.I.; Schrenk, D. Influence of redox-active compounds and PXR-activators on human MRP1 and MRP2 gene expression. Toxicology, 2002, 171(2-3), 137-146.
[55]
Haenisch, S.; Laechelt, S.; Bruckmueller, H.; Werk, A.; Noack, A.; Bruhn, O.; Remmler, C.; Cascorbi, I. Down-regulation of ATP-binding cassette C2 protein expression in HepG2 cells after rifampicin treatment is mediated by microRNA-379. Mol. Pharmacol., 2011, 80(2), 314-320.
[56]
Phillips, M.C. Molecular mechanisms of cellular cholesterol efflux. J. Biol. Chem., 2014, 289(35), 24020-24029.
[57]
Wang, H.; Liu, Y.; Zhu, L.; Wang, W.; Wan, Z.; Chen, F.; Wu, Y.; Zhou, J.; Yuan, Z. 17β-estradiol promotes cholesterol efflux from vascular smooth muscle cells through a liver X receptor α-dependent pathway. Int. J. Mol. Med., 2014, 33(3), 550-558.
[58]
Lu, N.Z.; Cidlowski, J.A. Glucocorticoid receptor isoforms generate transcription specificity. Trends Cell Biol., 2006, 16(6), 301-307.
[59]
Pavek, P.; Cerveny, L.; Svecova, L.; Brysch, M.; Libra, A.; Vrzal, R.; Nachtigal, P.; Staud, F.; Ulrichova, J.; Fendrich, Z.; Dvorak, Z. Examination of glucocorticoid receptor α-mediated transcriptional regulation of P-glycoprotein, CYP3A4, and CYP2C9 genes in placental trophoblast cell lines. Placenta, 2007, 28(10), 1004-1011.
[60]
Martin, P.; Riley, R.; Back, D.J.; Owen, A. Comparison of the induction profile for drug disposition proteins by typical nuclear receptor activators in human hepatic and intestinal cells. Br. J. Pharmacol., 2008, 153(4), 805-819.
[61]
Narang, V.S.; Fraga, C.; Kumar, N.; Shen, J.; Throm, S.; Stewart, C.F.; Waters, C.M. Dexamethasone increases expression and activity of multidrug resistance transporters at the rat blood-brain barrier. Am. J. Physiol. Cell Physiol., 2008, 295(2), C440-C450.
[62]
Honorat, M.; Mesnier, A.; Pietro, A., Di.; Lin, V.; Cohen, P.; Dumontet, C.; Payen, L. Dexamethasone down-regulates ABCG2 expression levels in breast cancer cells. Biochem. Biophys. Res. Commun., 2008, 375(3), 308-314.
[63]
Piekarz, R.L.; Cohen, D.; Horwitz, S.B. Progesterone regulates the murine multidrug resistance mdr1b gene. J. Biol. Chem., 1993, 268, 7613-7616.
[64]
Axiotis, C.; Guarch, R.; Merino, M.; Laporte, N.; Neumann, R. P-glycoprotein expression is increased in human secretory and gestational endometrium. Lab. Invest., 1991, 65(5), 577-581.
[65]
Fukuda, H.; He, P.J.; Yokota, K.; Soh, T.; Yamauchi, N.; Hattori, M.A. Progesterone-dependent and -independent expression of the multidrug resistance type I gene in porcine granulosa cells. Mol. Cell. Biochem., 2007, 298(1-2), 179-186.
[66]
Wang, H.; Lee, E.; Zhou, L.; Leung, P.C.K.; Ross, D.D.; Unadkat, J.D.; Mao, Q. Progesterone receptor (PR) isoforms PRA and PRB differentially regulate expression of the breast cancer resistance protein in human placental choriocarcinoma BeWo cells. Mol. Pharmacol., 2008, 73(3), 845-854.
[67]
Klaassen, C.D.; Aleksunes, L.M. Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation. Pharmacol. Rev., 2014, 62(1), 1-96.
[68]
Wu, X.; Zhang, X.; Sun, L.; Zhang, H.; Li, L.; Wang, X.; Li, W.; Su, P.; Hu, J.; Gao, P.; Zhou, G. Progesterone Negatively Regulates BCRP in Progesterone Receptor-Positive Human Breast Cancer Cells. Cell. Physiol. Biochem., 2013, 32, 344-354.
[69]
Wu, X.; Zhang, X.; Zhang, H.; Su, P.; Li, W.; Li, L.; Wang, Y.; Liu, W.; Gao, P.; Zhou, G. Progesterone receptor downregulates breast cancer resistance protein expression via binding to the progesterone response element in breast cancer. Cancer Sci., 2012, 103(5), 959-967.
[70]
Maher, J.M.; Cheng, X.; Tanaka, Y.; Scheffer, G.L.; Klaassen, C.D. Hormonal regulation of renal multidrug resistance-associated proteins 3 and 4 (Mrp3 and Mrp4) in mice. Biochem. Pharmacol., 2006, 71(10), 1470-1478.
[71]
Cai, C.; Omwancha, J.; Hsieh, C-L.; Shemshedini, L. Androgen induces expression of the multidrug resistance protein gene MRP4 in prostate cancer cells. Prostate Cancer Prostatic Dis., 2007, 10(1), 39-45.
[72]
Ho, L.; Kench, J.G.; Handelsman, D.J.; Scheffer, G.L.; Stricker, P.D.; Grygiel, J.G.; Sutherland, R.L.; Henshall, S.M.; Allen, J.D.; Horvath, L.G. Androgen regulation of multidrug resistance-associated protein 4 (MRP4/ABCC4) in prostate cancer. Prostate, 2008, 68(13), 1421-1429.
[73]
Suzuki, T.; Zhao, Y.L.; Nadai, M.; Naruhashi, K.; Shimizu, A.; Takagi, K.; Takagi, K.; Hasegawa, T. Gender-related differences in expression and function of hepatic P-glycoprotein and multidrug resistance-associated protein (Mrp2) in rats. Life Sci., 2006, 79(5), 455-461.
[74]
di Masi, A.; Marinis, E De .; Ascenzi, P.; Marino, M. Nuclear receptors CAR and PXR: Molecular, functional, and biomedical aspects. Mol. Aspects Med., 2009, 30(5), 297-343.
[75]
Tocchetti, G.N.; Rigalli, J.P.; Arana, M.R.; Villanueva, S.S.M.; Mottino, A.D. Modulation of expression and activity of intestinal multidrug resistance-associated protein 2 by xenobiotics. Toxicol. Appl. Pharmacol., 2016, 303, 45-57.
[76]
Lemmen, J.; Tozakidis, I.E.P.; Galla, H.J. Pregnane X receptor upregulates ABC-transporter Abcg2 and Abcb1 at the blood-brain barrier. Brain Res., 2013, 1491, 1-13.
[77]
Albermann, N.; Schmitz-Winnenthal, F.H.; Z’graggen, K.; Volk, C.; Hoffmann, M.M.; Haefeli, W.E.; Weiss, J. Expression of the drug transporters MDR1/ABCB1, MRP1/ABCC1, MRP2/ABCC2, BCRP/ABCG2, and PXR in peripheral blood mononuclear cells and their relationship with the expression in intestine and liver. Biochem. Pharmacol., 2005, 70(6), 949-958.
[78]
Teng, S.; Piquette-Miller, M. Hepatoprotective role of PXR activation and MRP3 in cholic acid-induced cholestasis. Br. J. Pharmacol., 2007, 151(3), 367-376.
[79]
Bauer, B.; Yang, X.; Hartz, A.M.S.; Olson, E.R.; Zhao, R.; Kalvass, J.C.; Pollack, G.M.; Miller, D.S. In vivo activation of human pregnane X receptor tightens the blood-brain barrier to methadone through P-glycoprotein up-regulation. Mol. Pharmacol., 2006, 70(4), 1212-1219.
[80]
Bauer, B.; Hartz, A.M.S.; Lucking, J.R.; Yang, X.; Pollack, G.M.; Miller, D.S. Coordinated nuclear receptor regulation of the efflux transporter, Mrp2, and the phase-II metabolizing enzyme, GSTp, at the blood-brain barrier. J. Cereb. Blood Flow Metab., 2008, 28, 1222-1234.
[81]
Geick, A.; Eichelbaum, M.; Burk, O. Nuclear Receptor Response Elements Mediate Induction of Intestinal MDR1 by Rifampin. J. Biol. Chem., 2001, 276(18), 14581-14587.
[82]
Kast, H.R.; Goodwin, B.; Tarr, P.T.; Jones, S.A.; Anisfeld, A.M.; Stoltz, C.M.; Tontonoz, P.; Kliewer, S.; Willson, T.M.; Edwards, P.A. Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor. J. Biol. Chem., 2002, 277(4), 2908-2915.
[83]
Greiner, B.; Eichelbaum, M.; Fritz, P.; Kreichgauer, H.P.; Von Richter, O.; Zundler, J.; Kroemer, H.K. The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. J. Clin. Invest., 1999, 104(2), 147-153.
[84]
Drescher, S.; Glaeser, H.; Mürdter, T.; Hitzl, M.; Eichelbaum, M.; Fromm, M.F. P-glycoprotein-mediated intestinal and biliary digoxin transport in humans. Clin. Pharmacol. Ther., 2003, 73(3), 223-231.
[85]
Fromm, M.F.; Kauffmann, H.M.; Fritz, P.; Burk, O.; Kroemer, H.K.; Warzok, R.W.; Eichelbaum, M.; Siegmund, W.; Schrenk, D. The effect of rifampin treatment on intestinal expression of human MRP transporters. Am. J. Pathol., 2000, 157(5), 1575-1580.
[86]
Fromm, M.F.; Eckhardt, K.; Li, S.; Schanzle, G.; Hofmann, U.; Mikus, G.; Eichelbaum, M. Loss of analgesic effect of morphine due to coadministration of rifampicin. Pain, 1997, 72, 261-267.
[87]
van de Wetering, K.; Zelcer, N.; Kuil, A.; Feddema, W.; Hillebrand, M.; Vlaming, M. L. H.; Schinkel, A. H.; Beijnen, J. H.; Borst, P. Multidrug resistance proteins 2 and 3 provide alternative routes for hepatic excretion of morphine-glucuronides. Mol. Pharmacol, 2007, 72, [2), 387-394.
[88]
Naesens, M.; Kuypers, D.R.J.; Streit, F.; Armstrong, V.W.; Oellerich, M.; Verbeke, K.; Vanrenterghem, Y. Rifampin induces alterations in mycophenolic acid glucuronidation and elimination: Implications for drug exposure in renal allograft recipients. Clin. Pharmacol. Ther., 2006, 80(5), 509-521.
[89]
Moore, L.B.; Goodwin, B.; Jones, S.; Wisely, G.; Serabjit-Singh, C.; Willson, T.; Collins, J.; Kliewer, S.St. John’s wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc. Natl. Acad. Sci. USA, 2000, 97(13), 7500-7502.
[90]
Dürr, D.; Stieger, B.; Kullak-Ublick, G.A.; Rentsch, K.M.; Steinert, H.C.; Meier, P.J.; Fattinger, K. St John’s Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4. Clin. Pharmacol. Ther., 2000, 68(6), 598-604.
[91]
Dresser, G.K.; Schwarz, U.I.; Wilkinson, G.R.; Kim, R.B. Coordinate induction of both cytochrome P4503A and MDR1 by St John’s wort in healthy subjects. Clin. Pharmacol. Ther., 2003, 73(1), 41-50.
[92]
Schwarz, U.I.; Hanso, H.; Oertel, R.; Miehlke, S.; Kuhlisch, E.; Glaeser, H.; Hitzl, M.; Dresser, G.K.; Kim, R.B.; Kirch, W. Induction of intestinal P-glycoprotein by St John’s wort reduces the oral bioavailability of talinolol. Clin. Pharmacol. Ther., 2007, 81(5), 669-678.
[93]
Bauer, S.; Störmer, E.; Johne, A.; Krüger, H.; Budde, K.; Neumayer, H.; Roots, I.; Mai, I. Alterations in cyclosporin A pharmacokinetics and metabolism during treatment with St John’s wort in renal transplant patients. Br. J. Clin. Pharmacol., 2003, 55(2), 203-211.
[94]
Ruschitzka, F.; Meier, P.J.; Turina, M.; Lüscher, T.F.; Noll, G. Acute heart transplant rejection due to Saint John’s wort. Lancet, 2000, 355(9203), 548-549.
[95]
Shibayama, Y.; Ikeda, R.; Motoya, T.; Yamada, K.St. John’s Wort (Hypericum perforatum) induces overexpression of multidrug resistance protein 2 (MRP2) in rats: A 30-day ingestion study. Food Chem. Toxicol., 2004, 42(6), 995-1002.
[96]
Gupta, A.; Mugundu, G.; Desai, P.B.; Thummel, K.E.; Unadkat, J.D. Intestinal human colon adenocarcinoma cell line, LS180, is an excellent model to study PXR-but not CAR-mediated CYP3A4 and MDR1 induction: studies with Anti-HIV Protease Inhibitors. Drug Metab. Dispos., 2008, 36(6), 1172-1180.
[97]
Weiss, J.; Haefeli, W.E. Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro. Int. J. Antimicrob. Agents, 2013, 41(5), 484-487.
[98]
Chan, G.N.Y.; Patel, R.; Cummins, C.L.; Bendayan, R. Induction of P-glycoprotein by antiretroviral drugs in human brain microvessel endothelial cells. Antimicrob. Agents Chemother., 2013, 57(9), 4481-4488.
[99]
Luo, G.; Cunningham, M.; Kim, S.; Burn, T.I.M.; Lin, J.; Sinz, M.; Hamilton, G.; Rizzo, C.; Jolley, S.; Gilbert, D.; Downey, A.; Mudra, D.; Graham, R.; Carroll, K.; Xie, J.; Madan, A.; Parkinson, A.; Christ, D.; Selling, B.; Lecluyse, E.; Gan, L. Cyp3a4 induction by drugs: Correlation between a pregnane x receptor reporter gene assay and Cyp3a4 expression in human hepatocytes. Drug Metab. Dispos., 2002, 30(7), 795-804.
[100]
Giessmann, T.; May, K.; Modess, C.; Wegner, D.; Hecker, U.; Zschiesche, M.; Dazert, P.; Grube, M.; Schroeder, E.; Warzok, R.; Cascorbi, I.; Kroemer, H.K.; Siegmund, W. Carbamazepine regulates intestinal P-glycoprotein and multidrug resistance protein MRP2 and influences disposition of talinolol in humans. Clin. Pharmacol. Ther., 2004, 76(3), 192-200.
[101]
Rigalli, J.P.; Ruiz, M.L.; Perdomo, V.G.; Villanueva, S.S.M.; Mottino, A.D.; Catania, V.A. Pregnane X receptor mediates the induction of P-glycoprotein by spironolactone in HepG2 cells. Toxicology, 2011, 285(1-2), 18-24.
[102]
Ghanem, C.I.; Gomez, P.C.; Arana, M.C.; Perassolo, M.; Delli Carpini, G.; Luquita, M.G.; Veggi, L.M.; Catania, V.A.; Bengochea, L.A.; Mottino, A.D. Induction of rat intestinal P-glycoprotein by spironolactone and its effect on absorption of orally administered digoxin. J. Pharmacol. Exp. Ther., 2006, 318(3), 1146-1152.
[103]
Satsu, H.; Hiura, Y.; Mochizuki, K.; Hamada, M.; Shimizu, M. Activation of Pregnane X Receptor and Induction of MDR1 by Dietary Phytochemicals Activation of Pregnane X Receptor and Induction of MDR1 by Dietary Phytochemicals. J. Agric. Food Chem., 2008, 56, 5366-5373.
[104]
Theile, D.; Hohmann, N.; Kiemel, D.; Gattuso, G.; Barreca, D.; Mikus, G.; Haefeli, W.E.; Schwenger, V.; Weiss, J. Clementine juice has the potential for drug interactions - In vitro comparison with grapefruit and mandarin juice. Eur. J. Pharm. Sci., 2017, 97, 247-256.
[105]
Rühl, R.; Sczech, R.; Landes, N.; Pfluger, P.; Kluth, D.; Schweigert, F.J. Carotenoids and their metabolites are naturally occurring activators of gene expression via the pregnane X receptor. Eur. J. Nutr., 2004, 43(6), 336-343.
[106]
Podszun, M.C.; Jakobi, M.; Birringer, M.; Weiss, J.; Frank, J. The long chain α-tocopherol metabolite α-13′-COOH and γ- tocotrienol induce P-glycoprotein expression and activity by activation of the pregnane X receptor in the intestinal cell line LS180. Mol. Nutr. Food Res., 2017, 61(3), 1-9.
[107]
Qiang, F.; Kang, K.; Han, H. Repeated dosing of piperine induced gene expression of P-glycoprotein via stimulated pregnane-X-receptor activity and altered pharmacokinetics of diltiazem in rats. Biopharm. Drug Dispos., 2012, 33, 446-454.
[108]
Harmsen, S.; Meijerman, I.; Febus, C.L.; Maas-Bakker, R.F.; Beijnen, J.H.; Schellens, J.H.M. PXR-mediated induction of P-glycoprotein by anticancer drugs in a human colon adenocarcinoma-derived cell line. Cancer Chemother. Pharmacol., 2010, 66, 765-771.
[109]
Harmsen, S.; Meijerman, I.; Maas-Bakker, R.F.; Beijnen, J.H.; Schellens, J.H.M. PXR-mediated P-glycoprotein induction by small molecule tyrosine kinase inhibitors. Eur. J. Pharm. Sci., 2013, 48(4-5), 644-649.
[110]
Jiang, H.; Chen, K.; He, J.; Pan, F.; Li, J.; Chen, J.; Chen, W.; Liang, H. Association of pregnane X receptor with multidrug resistance-related protein 3 and its role in human colon cancer chemoresistance. J. Gastrointest. Surg., 2009, 13(10), 1831-1838.
[111]
Chen, Y.; Tang, Y.; Chen, S.; Nie, D. Regulation of drug resistance by human pregnane X receptor in breast cancer. Cancer Biol. Ther., 2009, 8(13), 1265-1272.
[112]
Chen, Y.; Tang, Y.; Wang, M.T.; Zeng, S.; Nie, D. Human pregnane X receptor and resistance to chemotherapy in prostate cancer. Cancer Res., 2007, 67(21), 10361-10367.
[113]
Chen, Y.; Huang, W.; Chen, F.; Hu, G.; Li, F.; Li, J.; Xuan, A. Pregnane X receptors regulate CYP2C8 and P-glycoprotein to impact on the resistance of NSCLC cells to Taxol. Cancer Med., 2016, 5(12), 3564-3571.
[114]
Healan-Greenberg, C.; Waring, J.F.; Kempf, D.J.; Blomme, E.A.G.; Tirona, R.G.; Kim, R.B. A human immunodeficiency virus protease inhibitor is a novel functional inhibitor of human pregnane X receptor. Drug Metab. Dispos., 2008, 36(3), 500-507.
[115]
Svecova, L.; Vrzal, R.; Burysek, L.; Anzenbacherova, E.; Cerveny, L.; Grim, J.; Trejtnar, F.; Kunes, J.; Pour, M.; Staud, F.; Anzenbacher, P.; Dvorak, Z.; Pavek, P. Azole antimycotics differentially affect rifampicin-induced pregnane X receptor-mediated CYP3A4 gene expression. Drug Metab. Dispos., 2008, 36(2), 339-348.
[116]
Fuchs, I.; Hafner-Blumenstiel, V.; Markert, C.; Burhenne, J.; Weiss, J.; Haefeli, W.E.; Mikus, G. Effect of the CYP3A inhibitor ketoconazole on the PXR-mediated induction of CYP3A activity. Eur. J. Clin. Pharmacol., 2013, 69(3), 507-513.
[117]
Mooiman, K.D.; Maas-Bakker, R.F.; Moret, E.E.; Beijnen, J.H.; Schellens, J.H.M.; Meijerman, I. Milk thistle’s active components silybin and isosilybin: Novel inhibitors of PXR-mediated CYP3A4 induction. Drug Metab. Dispos., 2013, 41(8), 1494-1504.
[118]
Lim, Y.P.; Ma, C.Y.; Liu, C.L.; Lin, Y.H.; Hu, M.L.; Chen, J.J.; Hung, D.Z.; Hsieh, W.T.; Huang, J.D. Sesamin: A naturally occurring lignan inhibits CYP3A4 by antagonizing the pregnane X receptor activation. Evidence-based Complement. Altern. Med., 2012, 2012, 242810.
[119]
Deng, R.; Xu, C.; Chen, X.; Chen, P.; Wang, Y.; Zhou, X.; Jin, J.; Niu, L.; Ying, M.; Huang, M.; Bi, H. Resveratrol Suppresses the Inducible Expression of CYP3A4 Through the Pregnane X Receptor. J. Pharmacol. Sci., 2014, 126(2), 146-154.
[120]
Kwatra, D.; Venugopal, A.; Standing, D.; Ponnurangam, S.; Dhar, A.; Mitra, A.; Anant, S. Bitter melon extracts enhance the activity of chemotherapeutic agents through the modulation of multiple drug resistance. J. Pharm. Sci., 2013, 102(12), 4444-4454.
[121]
Doricakova, A.; Vrzal, R. A food contaminant ochratoxin A suppresses pregnane X receptor (PXR)-mediated CYP3A4 induction in primary cultures of human hepatocytes. Toxicology, 2015, 337, 72-78.
[122]
Burk, O.; Arnold, K.A.; Geick, A.; Tegude, H.; Eichelbaum, M. A role for constitutive androstane receptor in the regulation of human intestinal MDR1 expression. Biol. Chem., 2005, 386(6), 503-513.
[123]
Korjamo, T.; Mönkkönen, J.; Uusitalo, J.; Turpeinen, M.; Pelkonen, O.; Honkakoski, P. Metabolic and efflux properties of Caco-2 cells stably transfected with nuclear receptors. Pharm. Res., 2006, 23(9), 1991-2001.
[124]
Burk, O.; Arnold, K.A.; Nussler, A.K.; Schaeffeler, E.; Efimova, E.; Avery, B.A.; Avery, M.A.; Fromm, M.F.; Eichelbaum, M. Antimalarial artemisinin drugs induce cytochrome P450 and MDR1 expression by activation of xenosensors pregnane X receptor and constitutive androstane receptor. Mol. Pharmacol., 2005, 67(6), 1954-1965.
[125]
Li, Y.; Wang, Q.; Yao, X.; Li, Y. Induction of CYP3A4 and MDR1 gene expression by baicalin, baicalein, chlorogenic acid, and ginsenoside Rf through constitutive androstane receptor- and pregnane X receptor-mediated pathways. Eur. J. Pharmacol., 2010, 640(1-3), 46-54.
[126]
Jigorel, E.; Le Vee, M.; Boursier-Neyret, C.; Parmentier, Y.; Fardel, O. Differential regulation of sinusoidal and canalicular hepatic drug transporter expression by xenobiotics activating drug-sensing receptors in primary human hepatocytes. Drug Metab. Dispos., 2006, 34(10), 1756-1763.
[127]
Maher, J.M.; Cheng, X.; Slitt, A.L.; Dieter, M.Z.; Klaassen, C.D. Induction of the multidrug resistance-associated protein family of transporters by chemical activators of receptor-mediated pathways in mouse liver. Drug Metab. Dispos., 2005, 33(7), 956-962.
[128]
Aleksunes, L.M.; Klaassen, C.D. Coordinated regulation of hepatic phase-I and -II drug metabolizing genes and transporters using AhR-, CAR-, PXR-, PPARalpha-, and Nrf2-null mice. Drug Metab. Dispos., 2012, 40(7), 1366-1379.
[129]
Xiong, H.; Yoshinari, K.; Brouwer, K.L.R.; Negishi, M. Role of constitutive androstane receptor in the in vivo induction of Mrp3 And CYP2B1/2 by phenobarbital. Drug Metab. Dispos., 2002, 30(8), 918-923.
[130]
Cerveny, L.; Svecova, L.; Anzenbacherova, E.; Vrzal, R.; Staud, F.; Dvorak, Z.; Ulrichova, J.; Anzenbacher, P.; Pavek, P. Valproic acid induces CYP3A4 and MDR1 gene expression by activation of constitutive androstane receptor and pregnane X receptor pathways. Drug Metab. Dispos., 2007, 35(7), 1032-1041.
[131]
Wang, X.; Sykes, D.B.; Miller, D.S. Constitutive androstane receptor-mediated up-regulation of ATP-driven xenobiotic efflux transporters at the blood-brain barrier. Mol. Pharmacol., 2010, 78(3), 376-383.
[132]
Zhang, J.; Huang, W.; Chua, S.S.; Wei, P.; Moore, D.D. Modulation of acetaminophen-induced hepatotoxicity by the xenobiotic receptor CAR. Science, 2002, 298(5592), 422-424.
[133]
Slosky, L.M.; Thompson, B.J.; Sanchez-Covarrubias, L.; Zhang, Y.; Laracuente, M-L.; Vanderah, T.W.; Ronaldson, P.T.; Davis, T.P. Acetaminophen modulates P-glycoprotein functional expression at the blood-brain barrier by a constitutive androstane receptor-dependent mechanism. Mol. Pharmacol., 2013, 84(5), 774-786.
[134]
Lemmen, J.; Tozakidis, I.E.P.; Bele, P.; Galla, H.J. Constitutive androstane receptor upregulates Abcb1 and Abcg2 at the blood-brain barrier after CITCO activation. Brain Res., 2013, 1501, 68-80.
[135]
Assem, M.; Schuetz, E.G.; Leggas, M.; Sun, D.; Yasuda, K.; Reid, G.; Zelcer, N.; Adachi, M.; Strom, S.; Evans, R.M.; Moore, D.D.; Borst, P.; Schuetz, J.D. Interactions between hepatic Mrp4 and Sult2a as revealed by the constitutive androstane receptor and Mrp4 knockout mice. J. Biol. Chem., 2004, 279(21), 22250-22257.
[136]
Chai, J.; Luo, D.; Wu, X.; Wang, H.; He, Y.; Li, Q.; Zhang, Y.; Chen, L.; Peng, Z.H.; Xiao, T.; Wang, R.; Chen, W. Changes of organic anion transporter MRP4 and related nuclear receptors in human obstructive cholestasis. J. Gastrointest. Surg., 2011, 15(6), 996-1004.
[137]
Sberna, A.L.; Assem, M.; Gautier, T.; Grober, J.; Guiu, B.; Jeannin, A.; Pais De Barros, J.P.; Athias, A.; Lagrost, L.; Masson, D. Constitutive androstane receptor activation stimulates faecal bile acid excretion and reverse cholesterol transport in mice. J. Hepatol., 2011, 55(1), 154-161.
[138]
Huang, W.; Zhang, J.; Chua, S.S.; Qatanani, M.; Han, Y.; Granata, R.; Moore, D.D. Induction of bilirubin clearance by the constitutive androstane receptor (CAR). Proc. Natl. Acad. Sci. USA, 2003, 100(7), 4156-4161.
[139]
Tian, J.; Feng, Y.; Fu, H.; Xie, H.Q.; Jiang, J.X.; Zhao, B. The Aryl Hydrocarbon Receptor: A Key Bridging Molecule of External and Internal Chemical Signals. Environ. Sci. Technol., 2015, 49(16), 9518-9531.
[140]
Tan, K.P.; Wang, B.; Yang, M.; Boutros, P.C.; Macaulay, J.; Xu, H.; Chuang, A.I.; Kosuge, K.; Yamamoto, M.; Takahashi, S.; Wu, A.M.L.; Ross, D.D.; Harper, P.A.; Ito, S. Aryl hydrocarbon receptor is a transcriptional activator of the human breast cancer resistance protein (BCRP/ABCG2). Mol. Pharmacol., 2010, 78(2), 175-185.
[141]
Ebert, B.; Seidel, A.; Lampen, A. Identification of BCRP as transporter of benzo[a]pyrene conjugates metabolically formed in Caco-2 cells and its induction by Ah-receptor agonists. Carcinogenesis, 2005, 26(10), 1754-1763.
[142]
Tompkins, L.M.; Li, H.; Li, L.; Lynch, C.; Xie, Y.; Nakanishi, T.; Ross, D.D.; Wang, H. A novel xenobiotic responsive element regulated by aryl hydrocarbon receptor is involved in the induction of BCRP/ABCG2 in LS174T cells. Biochem. Pharmacol., 2010, 80(11), 1754-1761.
[143]
Halwachs, S.; Wassermann, L.; Lindner, S.; Zizzadoro, C.; Honscha, W. Fungicide prochloraz and environmental pollutant dioxin induce the ABCG2 transporter in bovine mammary epithelial cells by the arylhydrocarbon receptor signaling pathway. Toxicol. Sci., 2013, 131(2), 491-501.
[144]
Han, Y.; Sugiyama, Y. Expression and regulation of breast cancer resistance protein and multidrug resistance associated protein 2 in BALB/c mice. Biol. Pharm. Bull., 2006, 29(5), 1032-1035.
[145]
Theile, D.; Allendorf, D.; Köhler, B.C.; Jassowicz, A.; Weiss, J. Obatoclax as a perpetrator in drug-drug interactions and its efficacy in multidrug resistance cell lines. J. Pharm. Pharmacol., 2015, 67(11), 1575-1584.
[146]
To, K.K.W.; Robey, R.; Zhan, Z.; Bangiolo, L.; Bates, S.E. Upregulation of ABCG2 by Romidepsin via the Aryl Hydrocarbon Receptor Pathway. Mol. Cancer Res., 2011, 9(4), 516.
[147]
Xu, S.; Weerachayaphorn, J.; Cai, S-Y.; Soroka, C.J.; Boyer, J.L. Aryl hydrocarbon receptor and NF-E2-related factor 2 are key regulators of human MRP4 expression. Am. J. Physiol. Gastrointest. Liver Physiol., 2010, 299(1), G126-G135.
[148]
Wang, X.; Hawkins, B.T.; Miller, D.S. Aryl hydrocarbon receptor-mediated up-regulation of ATP-driven xenobiotic efflux transporters at the blood-brain barrier. FASEB J., 2011, 25(2), 644-652.
[149]
Hanada, K.; Nakai, K.; Tanaka, H.; Suzuki, F.; Kumada, H.; Ohno, Y.; Ozawa, S.; Ogata, H. Effect of nuclear receptor downregulation on hepatic expression of cytochrome P450 and transporters in chronic hepatitis C in association with fibrosis development. Drug Metab. Pharmacokinet., 2012, 27(3), 301-306.
[150]
DiNatale, B.C.; Smith, K.; John, K.; Krishnegowda, G.; Amin, S.G.; Perdew, G.H. Ah Receptor Antagonism Represses Head and Neck Tumor Cell Aggressive Phenotype. Mol. Cancer Res., 2012, 10(10), 1369-1379.
[151]
To, K.K.W.; Yu, L.; Liu, S.; Fu, J.; Cho, C.H. Constitutive AhR activation leads to concomitant ABCG2-mediated multidrug resistance in cisplatin-resistant esophageal carcinoma cells. Mol. Carcinog., 2012, 51(6), 449-464.
[152]
Derosa, G.; Sahebkar, A.; Maffioli, P. The Role of Various Peroxisome Proliferator-Activated Receptors and Their Ligands in Clinical Practice. J. Cell. Physiol., 2017, 9999, 1-9.
[153]
Kok, T.; Wolters, H.; Bloks, V.W.; Havinga, R.; Jansen, P.L.M.; Staels, B.; Kuipers, F. Induction of hepatic ABC transporter expression is part of the PPARα-mediated fasting response in the mouse. Gastroenterology, 2003, 124(1), 160-171.
[154]
Xia, X.; Jung, D.; Webb, P.; Zhang, A.; Zhang, B.; Li, L.; Ayers, S.D.; Gabbi, C.; Ueno, Y.; Gustafsson, J.Å.; Alpini, G.; Moore, D.D.; Lesage, G.D. Liver X receptor β and peroxisome proliferator-activated receptor δ regulate cholesterol transport in murine cholangiocytes. Hepatology, 2012, 56(6), 2288-2296.
[155]
Aleksunes, L.M.; Xu, J.; Lin, E.; Wen, X.; Goedken, M.J.; Slitt, A.L. Pregnancy represses induction of efflux transporters in livers of type I diabetic mice. Pharm. Res., 2013, 30(9), 2209-2220.
[156]
Moffit, J.S.; Aleksunes, L.M.; Maher, J.M.; Scheffer, G.L.; Klaassen, C.D.; Manautou, J.E. Induction of hepatic transporters multidrug resistance-associated proteins (Mrp) 3 and 4 by clofibrate is regulated by peroxisome proliferator-activated receptor alpha. J. Pharmacol. Exp. Ther., 2006, 317(2), 537-545.
[157]
Bigo, C.; Kaeding, J.; El Husseini, D.; Rudkowska, I.; Verreault, M.; Vohl, M.C.; Barbier, O. PPARα: A master regulator of bilirubin homeostasis. PPAR Res., 2014, 2014, 747014.
[158]
More, V.R.; Campos, C.R.; Evans, R. a; Oliver, K. D.; Chan, G. N.; Miller, D. S.; Cannon, R. E. PPAR-α, a lipid-sensing transcription factor, regulates blood-brain barrier efflux transporter expression. J. Cereb. Blood Flow Metab., 2017, 37(4), 1199-1212.
[159]
Hoque, M.T.; Robillard, K.R.; Bendayan, R. Regulation of breast cancer resistance protein by peroxisome proliferator-activated receptor α in human brain microvessel endothelial cells. Mol. Pharmacol., 2012, 81(4), 598-609.
[160]
Lin, Y.; Bircsak, K.M.; Gorczyca, L.; Wen, X.; Aleksunes, L.M. Regulation of the placental BCRP transporter by PPAR gamma. J. Biochem. Mol. Toxicol., 2016, 31(5)
[http://dx.doi.org/10.1002/jbt.21880]
[161]
Ma, Z.; Deng, C.; Hu, W.; Zhou, J.; Fan, C.; Di, S.; Liu, D.; Yang, Y.; Wang, D. Liver X receptors and their agonists: Targeting for cholesterol homeostasis and cardiovascular diseases. Curr. Issues Mol. Biol., 2017, 22, 41-64.
[162]
Huwait, E.A.; Greenow, K.R.; Singh, N.N.; Ramji, D.P. A novel role for c-Jun N-terminal kinase and phosphoinositide 3-kinase in the liver X receptor-mediated induction of macrophage gene expression. Cell. Signal., 2011, 23(3), 542-549.
[163]
Huwait, E.A.; Singh, N.N.; Michael, D.R.; Davies, T.S.; Moss, J.W.E.; Ramji, D.P. Protein kinase C is involved in the induction of ATP-binding cassette transporter A1 expression by liver X receptor/retinoid X receptor agonist in human macrophages. J. Cell. Biochem., 2015, 116(9), 2032-2038.
[164]
Murthy, S.; Born, E.; Mathur, S.N.; Field, F.J. LXR/RXR activation enhances basolateral efflux of cholesterol in CaCo-2 cells. J. Lipid Res., 2002, 43(7), 1054-1064.
[165]
Akanuma, S. ichi; Hori, S.; Ohtsuki, S.; Fujiyoshi, M.; Terasaki, T. Expression of nuclear receptor mRNA and liver X receptor-mediated regulation of ABC transporter A1 at rat blood-brain barrier. Neurochem. Int., 2008, 52(4-5), 669-674.
[166]
Chisaki, I.; Kobayashi, M.; Itagaki, S.; Hirano, T.; Iseki, K. Liver X receptor regulates expression of MRP2 but not that of MDR1 and BCRP in the liver. Biochim. Biophys. Acta, 2009, 1788(11), 2396-2403.
[167]
Parks, D.; Blanchard, S.; Bledsoe, R.; Chandra, G.; Consler, T.; Kliewer, S.; Stimmel, J.; Willson, T.; Zavacki, A.; Moore, D.; Lehmann, J. Bile Acids: Natural Ligands for an Orphan Nuclear Receptor. Science, 1999, 284, 1365-1368.
[168]
Lu, T.T.; Repa, J.J.; Mangelsdorf, D.J. Orphan nuclear receptors as eLiXiRs and FiXeRs of sterol metabolism. J. Biol. Chem., 2001, 276(41), 37735-37738.
[169]
Sinal, C.J.; Tohkin, M.; Miyata, M.; Ward, J.M.; Lambert, G.; Gonzalez, F.J. Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell, 2000, 102(6), 731-744.
[170]
Schuetz, E.G.; Strom, S.; Yasuda, K.; Lecureur, V.; Assem, M.; Brimer, C.; Lamba, J.; Kim, R.B.; Ramachandran, V.; Komoroski, B.J.; Venkataramanan, R.; Cai, H.; Sinal, C.J.; Gonzalez, F.J.; Schuetz, J.D. Disrupted bile acid homeostasis reveals an unexpected interaction among nuclear hormone receptors, transporters, and cytochrome P450. J. Biol. Chem., 2001, 276(42), 39411-39418.
[171]
Ananthanarayanan, M.; Balasubramanian, N.; Makishima, M.; Mangelsdorf, D.J.; Suchy, F.J. Human bile salt export pump promoter is transactivated by the farnesoid X receptor/bile acid receptor. J. Biol. Chem., 2001, 276(31), 28857-28865.
[172]
Plass, J.R.M.; Mol, O.; Heegsma, J.; Geuken, M.; Faber, K.N.; Jansen, P.L.M.; Müller, M. Farnesoid X receptor and bile salts are involved in transcriptional regulation of the gene encoding the human bile salt export pump. Hepatology, 2002, 35(3), 589-596.
[173]
Gomez-Ospina, N.; Potter, C.; Xiao, R.; Manickam, K.; Kim, M.; Kim, K.; Shneider, B.; Picarsic, J.; Jacobson, T.; Zhang, J.; He, W.; Liu, P.; Knisely, A.; Finegold, M.; Muzny, D.; Boerwinkle, E.; Lupski, J.; Plon, S.; Gibbs, R.; Eng, C.; Yang, Y.; Washington, G.; Porteus, M.; Berquist, W.; Kambham, N.; Singh, R.; Xia, F.; Enns, G.; Moore, D. Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis. Nat. Commun., 2016, 7, 1-8.
[174]
Geier, A.; Dietrich, C.G.; Voigt, S.; Ananthanarayanan, M.; Lammert, F.; Schmitz, A.; Trauner, M.; Wasmuth, H.E.; Boraschi, D.; Balasubramaniyan, N.; Suchy, F.J.; Matern, S.; Gartung, C. Cytokine-dependent regulation of hepatic organic anion transporter gene transactivators in mouse liver. Am. J. Physiol. Gastrointest. Liver Physiol., 2005, 289, G831-G841.
[175]
Abu-Hayyeh, S.; Papacleovoulou, G.; Lövgren-Sandblom, A.; Tahir, M.; Oduwole, O.; Jamaludin, N.A.; Ravat, S.; Nikolova, V.; Chambers, J.; Selden, C.; Rees, M.; Marschall, H.U.; Parker, M.G.; Williamson, C. Intrahepatic cholestasis of pregnancy levels of sulfated progesterone metabolites inhibit farnesoid X receptor resulting in a cholestatic phenotype. Hepatology, 2013, 57(2), 716-726.
[176]
Balasubramaniyan, N.; Luo, Y.; Sun, A.Q.; Suchy, F.J. SUMOylation of the farnesoid X receptor (FXR) regulates the expression of FXR target genes. J. Biol. Chem., 2013, 288(19), 13850-13862.
[177]
Chen, Y.; Song, X.; Valanejad, L.; Vasilenko, A.; More, V.; Qiu, X.; Chen, W.; Lai, Y.; Slitt, A.; Stoner, M.; Yan, B.; Deng, R. Bile salt export pump is dysregulated with altered farnesoid X receptor isoform expression in patients with hepatocellular carcinoma. Hepatology, 2013, 57(4), 1530-1541.
[178]
Deng, R.; Yang, D.; Yang, J.; Yan, B. Oxysterol 22 (R)-hydroxycholesterol induces the expression of the bile salt export pump through nuclear receptor farsenoid X receptor but not liver X receptor. J. Pharmacol. Exp. Ther., 2006, 317(1), 317-325.
[179]
Zhao, A.; Yu, J.; Lew, J-L.; Huang, L.; Wright, S.D.; Cui, J. Polyunsaturated fatty acids are FXR ligands and differentially regulate expression of FXR targets. DNA Cell Biol., 2004, 23(8), 519-526.
[180]
Swales, K.E.; Korbonits, M.; Carpenter, R.; Walsh, D.T.; Warner, T.D.; Bishop-Bailey, D. The farnesoid X receptor is expressed in breast cancer and regulates apoptosis and aromatase expression. Cancer Res., 2006, 66(20), 10120-10126.
[181]
Herraez, E.; Gonzalez-Sanchez, E.; Vaquero, J.; Romero, M.R.; Serrano, M.A.; Marin, J.J.G.; Briz, O. Cisplatin-induced chemoresistance in colon cancer cells involves FXR-dependent and FXR-independent up-regulation of ABC proteins. Mol. Pharm., 2012, 9(9), 2565-2576.
[182]
Uray, I.P.; Dmitrovsky, E.; Brown, P.H. Retinoids and rexinoids in cancer prevention: From laboratory to clinic. Semin. Oncol., 2016, 43(1), 49-64.
[183]
Breier, A.; Stetka, J.; Bohacova, V.; Macejova, D.; Brtko, J.; Sulova, Z. Effect of 9-cis retinoic acid and all-trans retinoic acid in combination with verapamil on P-glycoprotein expression in L1210 cells. Neoplasma, 2014, 61(5), 553-565.
[184]
Stromskaya, T.P.; Rybalkina, E.Y.; Shtil, A.A.; Zabotina, T.N.; Filippova, N.A.; Stavrovskaya, A.A. Influence of exogenous RAR alpha gene on MDR1 expression and P-glycoprotein function in human and rodent cell lines. Br. J. Cancer, 1998, 77(11), 1718-1725.
[185]
Denson, L.A.; Bohan, A.; Held, M.A.; Boyer, J.L. Organ-specific alterations in RARα:RXRα abundance regulate rat Mrp2 (Abcc2) expression in obstructive cholestasis. Gastroenterology, 2002, 123(2), 599-607.
[186]
Hessel, S.; Lampen, A. All-trans retinoic acid enhances the transport of phase II metabolites of benzo[a]pyrene by inducing the Breast Cancer Resistance Protein expression in Caco-2 cells. Toxicol. Lett., 2010, 197(2), 151-155.
[187]
Costet, P.; Lalanne, F.; Gerbod-Giannone, M.C.; Molina, J.R.; Fu, X.; Lund, E.G.; Gudas, L.J.; Tall, A.R. Retinoic acid receptor-mediated induction of ABCA1 in macrophages. Mol. Cell. Biol., 2003, 23(21), 7756-7766.
[188]
Germain, P.; Chambon, P.; Eichele, G.; Evans, R.M.; Lazar, M. a; Leid, M.; De Lera, A. R.; Lotan, R.; Mangelsdorf, D. J.; Gronemeyer, H. International Union of Pharmacology. LXIII. Retinoid X receptors. Pharmacol. Rev., 2006, 58(4), 760-772.
[189]
Chen, J.; Costa, L.G.; Guizzetti, M. Retinoic Acid Isomers Up-Regulate ATP Binding Cassette A1 and G1 and Cholesterol Efflux in Rat Astrocytes: Implications for Their Therapeutic and Teratogenic Effects. J. Pharmacol. Exp. Ther., 2011, 338(3), 870-878.
[190]
Sun, Y.; Fan, J.; Zhu, Z.; Guo, X.; Zhou, T.; Duan, W.; Shen, X. Small molecule TBTC as a new selective retinoid X receptor α agonist improves behavioral deficit in Alzheimer’s disease model mice. Eur. J. Pharmacol., 2015, 762(1), 202-213.
[191]
Hoeke, M.O.; Plass, J.R.M.; Heegsma, J.; Geuken, M.; van Rijsbergen, D.; Baller, J.F.W.; Kuipers, F.; Moshage, H.; Jansen, P.L.M.; Faber, K.N. Low retinol levels differentially modulate bile salt-induced expression of human and mouse hepatic bile salt transporters. Hepatology, 2009, 49(1), 151-159.
[192]
Cermanova, J.; Kadova, Z.; Zagorova, M.; Hroch, M.; Tomsik, P.; Nachtigal, P.; Kudlackova, Z.; Pavek, P.; Dubecka, M.; Ceckova, M.; Staud, F.; Laho, T.; Micuda, S. Boldine enhances bile production in rats via osmotic and farnesoid X receptor dependent mechanisms. Toxicol. Appl. Pharmacol., 2015, 285(1), 12-22.
[193]
Liu, Y.; Binz, J.; Numerick, M.J.; Dennis, S.; Luo, G.; Desai, B.; MacKenzie, K.I.; Mansfield, T.A.; Kliewer, S.A.; Goodwin, B.; Jones, S.A. Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasis. J. Clin. Invest., 2003, 112(11), 1678-1687.
[194]
ClinicalTrials.gov. Phase 4 Study of Obeticholic Acid Evaluating Clinical Outcomes in Patients With Primary Biliary Cholangitis (COBALT). https://clinicaltrials.gov/ct2/ show/NCT02308111 (Accessed July 20, 2017).
[195]
Chen, P.; Li, J.; Fan, X.; Zeng, H.; Deng, R.; Li, D.; Huang, M.; Bi, H. Oleanolic acid attenuates obstructive cholestasis in bile duct-ligated mice, possibly via activation of NRF2-MRPs and FXR antagonism. Eur. J. Pharmacol., 2015, 765, 131-139.
[196]
Plat, J.; Mensink, R.P. Increased intestinal ABCA1 expression contributes to the decrease in cholesterol absorption after plant stanol consumption. FASEB J., 2002, 16(10), 1248-1253.
[197]
De Smet, E.; Mensink, R.P.; Plat, J. Effects of plant sterols and stanols on intestinal cholesterol metabolism: suggested mechanisms from past to present. Mol. Nutr. Food Res., 2012, 56(7), 1058-1072.
[198]
Cedó, L.; Santos, D.; Ludwig, I.A.; Silvennoinen, R.; García-León, A.; Kaipiainen, L.; Carbó, J.M.; Valledor, A.F.; Gylling, H.; Motilva, M.J.; Kovanen, P.T.; Lee-Rueckert, M.; Blanco-Vaca, F.; Escolà-Gil, J.C. Phytosterol-mediated inhibition of intestinal cholesterol absorption in mice is independent of liver X receptor. Mol. Nutr. Food Res., 2017, 61(9)
[http://dx.doi.org/10.1002/mnfr.201700055]


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VOLUME: 26
ISSUE: 7
Year: 2019
Page: [1079 - 1112]
Pages: 34
DOI: 10.2174/0929867324666170920141707
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