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Xenobiotica
the fate of foreign compounds in biological systems
Volume 41, 2011 - Issue 7
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General Xenobiochemistry

The statin class of HMG-CoA reductase inhibitors demonstrate differential activation of the nuclear receptors PXR, CAR and FXR, as well as their downstream target genes

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Pages 519-529 | Received 11 Jan 2011, Accepted 04 Mar 2011, Published online: 09 Apr 2011

References

  • Aouabdi S, Gibson G, Plant N. (2006). Transcriptional regulation of the PXR gene: identification and characterization of a functional peroxisome proliferator-activated receptor alpha binding site within the proximal promoter of PXR. Drug Metab Dispos 34:138–144.
  • Billecke S, Draganov D, Counsell R, Stetson P, Watson C, Hsu C, La Du BN. (2000). Human serum paraoxonase (PON1) isozymes Q and R hydrolyze lactones and cyclic carbonate esters. Drug Metab Dispos 28:1335–1342.
  • Bonofiglio D, Gabriele S, Aquila S, Catalano S, Gentile M, Middea E, Giordano F, Andò S. (2005). Estrogen receptor alpha binds to peroxisome proliferator-activated receptor response element and negatively interferes with peroxisome proliferator-activated receptor gamma signaling in breast cancer cells. Clin Cancer Res 11:6139–6147.
  • Bookout AL, Jeong Y, Downes M, Yu RT, Evans RM, Mangelsdorf DJ. (2006). Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network. Cell 126:789–799.
  • Chrencik JE, Orans J, Moore LB, Xue Y, Peng L, Collins JL, Wisely GB, Lambert MH, Kliewer SA, Redinbo MR. (2005). Structural disorder in the complex of human pregnane X receptor and the macrolide antibiotic rifampicin. Mol Endocrinol 19:1125–1134.
  • Dietschy JM, Wilson JD. (1970). Regulation of cholesterol metabolism. N Engl J Med 282:1179–1183.
  • Ding X, Staudinger JL. (2005). The ratio of constitutive androstane receptor to pregnane X receptor determines the activity of guggulsterone against the Cyp2b10 promoter. J Pharmacol Exp Ther 314:120–127.
  • Ekins S, Erickson JA. (2002). A pharmacophore for human pregnane X receptor ligands. Drug Metab Dispos 30:96–99.
  • El-Sankary W, Gibson GG, Ayrton A, Plant N. (2001). Use of a reporter gene assay to predict and rank the potency and efficacy of CYP3A4 inducers. Drug Metab Dispos 29:1499–1504.
  • Everett DW, Chando TJ, Didonato GC, Singhvi SM, Pan HY, Weinstein SH. (1991). Biotransformation of pravastatin sodium in humans. Drug Metab Dispos 19:740–748.
  • Goodwin B, Hodgson E, Liddle C. (1999). The orphan human pregnane X receptor mediates the transcriptional activation of CYP3A4 by rifampicin through a distal enhancer module. Mol Pharmacol 56:1329–1339.
  • Habeos I, Ziros PG, Psyrogiannis A, Vagenakis AG, Papavassiliou AG. (2005). Statins and transcriptional regulation: the FXR connection. Biochem Biophys Res Commun 334:601–605.
  • Handschin C, Meyer UA. (2005). Regulatory network of lipid-sensing nuclear receptors: roles for CAR, PXR, LXR, and FXR. Arch Biochem Biophys 433:387–396.
  • Hirano M, Maeda K, Matsushima S, Nozaki Y, Kusuhara H, Sugiyama Y. (2005). Involvement of BCRP (ABCG2) in the biliary excretion of pitavastatin. Mol Pharmacol 68:800–807.
  • Ho RH, Tirona RG, Leake BF, Glaeser H, Lee W, Lemke CJ, Wang Y, Kim RB. (2006). Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Gastroenterology 130:1793–1806.
  • Holdgate GA, Ward WH, McTaggart F. (2003). Molecular mechanism for inhibition of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase by rosuvastatin. Biochem Soc Trans 31:528–531.
  • Ishigami M, Honda T, Takasaki W, Ikeda T, Komai T, Ito K, Sugiyama Y. (2001). A comparison of the effects of 3-hydroxy-3-methylglutaryl-coenzyme a (HMG-CoA) reductase inhibitors on the CYP3A4-dependent oxidation of mexazolam in vitro. Drug Metab Dispos 29:282–288.
  • Kobayashi K, Yamanaka Y, Iwazaki N, Nakajo I, Hosokawa M, Negishi M, Chiba K. (2005). Identification of HMG-CoA reductase inhibitors as activators for human, mouse and rat constitutive androstane receptor. Drug Metab Dispos 33:924–929.
  • Lennernäs H, Fager G. (1997). Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors. Similarities and differences. Clin Pharmacokinet 32:403–425.
  • Linsel-Nitschke P, Tall AR. (2005). HDL as a target in the treatment of atherosclerotic cardiovascular disease. Nat Rev Drug Discov 4:193–205.
  • Maglich JM, Parks DJ, Moore LB, Collins JL, Goodwin B, Billin AN, Stoltz CA, Kliewer SA, Lambert MH, Willson TM, Moore JT. (2003). Identification of a novel human constitutive androstane receptor (CAR) agonist and its use in the identification of CAR target genes. J Biol Chem 278:17277–17283.
  • Maglich JM, Stoltz CM, Goodwin B, Hawkins-Brown D, Moore JT, Kliewer SA. (2002). Nuclear pregnane x receptor and constitutive androstane receptor regulate overlapping but distinct sets of genes involved in xenobiotic detoxification. Mol Pharmacol 62:638–646.
  • Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ. (2009). AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem 30:2785–2791.
  • Nakabayashi H, Taketa K, Miyano K, Yamane T, Sato J. (1982). Growth of human hepatoma cells lines with differentiated functions in chemically defined medium. Cancer Res 42:3858–3863.
  • Nakai D, Nakagomi R, Furuta Y, Tokui T, Abe T, Ikeda T, Nishimura K. (2001). Human liver-specific organic anion transporter, LST-1, mediates uptake of pravastatin by human hepatocytes. J Pharmacol Exp Ther 297:861–867.
  • Neuvonen PJ, Niemi M, Backman JT. (2006). Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther 80:565–581.
  • Olsson AG, Pears J, McKellar J, Mizan J, Raza A. (2001). Effect of rosuvastatin on low-density lipoprotein cholesterol in patients with hypercholesterolemia. Am J Cardiol 88:504–508.
  • Pascussi JM, Busson-Le Coniat M, Maurel P, Vilarem MJ. (2003). Transcriptional analysis of the orphan nuclear receptor constitutive androstane receptor (NR1I3) gene promoter: identification of a distal glucocorticoid response element. Mol Endocrinol 17:42–55.
  • Plant N. (2004). Interaction networks: coordinating responses to xenobiotic exposure. Toxicology 202:21–32.
  • Plant N. (2007). The human cytochrome P450 sub-family: transcriptional regulation, inter-individual variation and interaction networks. Biochim Biophys Acta 1770:478–488.
  • Plant N, Aouabdi S. (2009). Nuclear receptors: the controlling force in drug metabolism of the liver? Xenobiotica 39:597–605.
  • Raucy J, Warfe L, Yueh MF, Allen SW. (2002). A cell-based reporter gene assay for determining induction of CYP3A4 in a high-volume system. J Pharmacol Exp Ther 303:412–423.
  • Rizzo G, Renga B, Mencarelli A, Pellicciari R, Fiorucci S. (2005). Role of FXR in regulating bile acid homeostasis and relevance for human diseases. Curr Drug Targets Immune Endocr Metabol Disord 5:289–303.
  • Sirvent P, Mercier J, Lacampagne A. (2008). New insights into mechanisms of statin-associated myotoxicity. Curr Opin Pharmacol 8:333–338.
  • Vaklavas C, Chatzizisis YS, Ziakas A, Zamboulis C, Giannoglou GD. (2009). Molecular basis of statin-associated myopathy. Atherosclerosis 202:18–28.
  • Wagner M, Halilbasic E, Marschall HU, Zollner G, Fickert P, Langner C, Zatloukal K, Denk H, Trauner M. (2005). CAR and PXR agonists stimulate hepatic bile acid and bilirubin detoxification and elimination pathways in mice. Hepatology 42:420–430.
  • Watanabe H, Kosuge K, Nishio S, Yamada H, Uchida S, Satoh H, Hayashi H, Ishizaki T, Ohashi K. (2004). Pharmacokinetic and pharmacodynamic interactions between simvastatin and diltiazem in patients with hypercholesterolemia and hypertension. Life Sci 76:281–292.
  • Yamasaki D, Nakamura T, Okamura N, Kokudai M, Inui N, Takeuchi K, Watanabe H, Hirai M, Okumura K, Sakaeda T. (2009). Effects of acid and lactone forms of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on the induction of MDR1 expression and function in LS180 cells. Eur J Pharm Sci 37:126–132.

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