Masahiko Negishi

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. pmc Liganded pregnane X receptor represses the human sulfotransferase SULT1E1 promoter through disrupting its chromatin structure
    Susumu Kodama
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    Nucleic Acids Res 39:8392-403. 2011
  2. pmc Nuclear receptor CAR represses TNFalpha-induced cell death by interacting with the anti-apoptotic GADD45B
    Yukio Yamamoto
    Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America
    PLoS ONE 5:e10121. 2010
  3. pmc Serine 216 Phosphorylation of Estrogen Receptor α in Neutrophils: Migration and Infiltration into the Mouse Uterus
    Sawako Shindo
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America
    PLoS ONE 8:e84462. 2013
  4. ncbi request reprint Glucosaminylglycan biosynthesis: what we can learn from the X-ray crystal structures of glycosyltransferases GlcAT1 and EXTL2
    Masahiko Negishi
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Biochem Biophys Res Commun 303:393-8. 2003
  5. ncbi request reprint Structure and function of sulfotransferases
    M Negishi
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institutes of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    Arch Biochem Biophys 390:149-57. 2001
  6. ncbi request reprint Cytoplasmic localization of pregnane X receptor and ligand-dependent nuclear translocation in mouse liver
    E James Squires
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 279:49307-14. 2004
  7. ncbi request reprint Human CYP2C8 is transcriptionally regulated by the nuclear receptors constitutive androstane receptor, pregnane X receptor, glucocorticoid receptor, and hepatic nuclear factor 4alpha
    Stephen S Ferguson
    Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Mol Pharmacol 68:747-57. 2005
  8. pmc Overexpression of the Rho-guanine nucleotide exchange factor ECT2 inhibits nuclear translocation of nuclear receptor CAR in the mouse liver
    Fardin Hosseinpour
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, United States
    FEBS Lett 581:4937-42. 2007
  9. pmc Cohesin protein SMC1 represses the nuclear receptor CAR-mediated synergistic activation of a human P450 gene by xenobiotics
    Kaoru Inoue
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Biochem J 398:125-33. 2006
  10. ncbi request reprint Crystal structure of an alpha 1,4-N-acetylhexosaminyltransferase (EXTL2), a member of the exostosin gene family involved in heparan sulfate biosynthesis
    Lars C Pedersen
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 278:14420-8. 2003

Collaborators

Detail Information

Publications107 found, 100 shown here

  1. pmc Liganded pregnane X receptor represses the human sulfotransferase SULT1E1 promoter through disrupting its chromatin structure
    Susumu Kodama
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    Nucleic Acids Res 39:8392-403. 2011
    ..Removal of the DR sites from the enhancer hampers the ability of HNF4α to loop the promoter and that of PXR to repress the promoter activity. Thus, PXR represses human SULT1E1, possibly attenuating the inactivation of estrogen...
  2. pmc Nuclear receptor CAR represses TNFalpha-induced cell death by interacting with the anti-apoptotic GADD45B
    Yukio Yamamoto
    Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America
    PLoS ONE 5:e10121. 2010
    ..Here we have identified Growth Arrest and DNA Damage-inducible 45beta (GADD45B) as a novel CAR target, through which CAR represses cell death...
  3. pmc Serine 216 Phosphorylation of Estrogen Receptor α in Neutrophils: Migration and Infiltration into the Mouse Uterus
    Sawako Shindo
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America
    PLoS ONE 8:e84462. 2013
    ..Serine 216 is the conserved phosphorylation site within the DNA binding domains found in the majority of nuclear receptors...
  4. ncbi request reprint Glucosaminylglycan biosynthesis: what we can learn from the X-ray crystal structures of glycosyltransferases GlcAT1 and EXTL2
    Masahiko Negishi
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Biochem Biophys Res Commun 303:393-8. 2003
    ..Adaptive binding of the disaccharide moiety of the acceptor sugars enables the enzymes to catalyze either an inverting S(N)2-type displacement reaction or a retaining S(N)i-like transfer reaction...
  5. ncbi request reprint Structure and function of sulfotransferases
    M Negishi
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institutes of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    Arch Biochem Biophys 390:149-57. 2001
    ..The X-ray crystal structures have opened a new era for the study of sulfotransferases...
  6. ncbi request reprint Cytoplasmic localization of pregnane X receptor and ligand-dependent nuclear translocation in mouse liver
    E James Squires
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 279:49307-14. 2004
    ..We conclude that the CCRP mediates the retention of PXR in the cytosol and modulates the activation of PXR in response to PCN treatment...
  7. ncbi request reprint Human CYP2C8 is transcriptionally regulated by the nuclear receptors constitutive androstane receptor, pregnane X receptor, glucocorticoid receptor, and hepatic nuclear factor 4alpha
    Stephen S Ferguson
    Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Mol Pharmacol 68:747-57. 2005
    ..In summary, the present studies show that CAR, PXR, GR, and HNF4alpha can regulate CYP2C8 expression and identify specific cis-elements within the promoter that control these regulatory pathways...
  8. pmc Overexpression of the Rho-guanine nucleotide exchange factor ECT2 inhibits nuclear translocation of nuclear receptor CAR in the mouse liver
    Fardin Hosseinpour
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, United States
    FEBS Lett 581:4937-42. 2007
    ..CAR directly bound to the PH domain. Thus, ECT2 may comprise a part of the PB response signal regulating the intracellular trafficking of CAR...
  9. pmc Cohesin protein SMC1 represses the nuclear receptor CAR-mediated synergistic activation of a human P450 gene by xenobiotics
    Kaoru Inoue
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Biochem J 398:125-33. 2006
    ..These results are consistent with the conclusion that SMC1 binding represses OARE activity and its dissociation allows the recruitment of CAR to the OARE, synergizing PBREM activity and the expression of the CYP2B6 gene...
  10. ncbi request reprint Crystal structure of an alpha 1,4-N-acetylhexosaminyltransferase (EXTL2), a member of the exostosin gene family involved in heparan sulfate biosynthesis
    Lars C Pedersen
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 278:14420-8. 2003
    ..These structures represent the first structures from the exostosin gene family and provide important insight into the mechanisms of alpha1,4-N-acetylhexosaminyl transfer in heparan biosynthesis...
  11. pmc Dephosphorylation of threonine 38 is required for nuclear translocation and activation of human xenobiotic receptor CAR (NR1I3)
    Shingo Mutoh
    Laboratories of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 284:34785-92. 2009
    ..These results define CAR as a cell signal-regulated constitutive active nuclear receptor. These results also provide phosphorylation/dephosphorylation of the threonine as the primary drug target for CAR activation...
  12. doi request reprint PPP1R16A, the membrane subunit of protein phosphatase 1beta, signals nuclear translocation of the nuclear receptor constitutive active/androstane receptor
    Tatsuya Sueyoshi
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Mol Pharmacol 73:1113-21. 2008
    ....
  13. ncbi request reprint Structural analysis of the sulfotransferase (3-o-sulfotransferase isoform 3) involved in the biosynthesis of an entry receptor for herpes simplex virus 1
    Andrea F Moon
    Laboratories of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 279:45185-93. 2004
    ..These residues participate in the substrate recognition of 3-OST-3. This structure provides atomic level evidence for delineating the substrate recognition and catalytic mechanism for 3-OST-3...
  14. ncbi request reprint Complementary roles of farnesoid X receptor, pregnane X receptor, and constitutive androstane receptor in protection against bile acid toxicity
    Grace L Guo
    Laboratory of Metabolism, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 278:45062-71. 2003
    ..Furthermore, FXR, PXR, and CAR protect against hepatic bile acid toxicity in a complementary manner, suggesting that they serve as redundant but distinct layers of defense to prevent overt hepatic damage by bile acids during cholestasis...
  15. pmc Phenytoin induction of the cyp2c37 gene is mediated by the constitutive androstane receptor
    Jonathan P Jackson
    Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
    Drug Metab Dispos 34:2003-10. 2006
    ..Mutation of this CAR-RE abolished mouse CAR transactivation of a Cyp2c37 -2.9-kilobase pair luciferase reporter construct in HepG2 cells...
  16. ncbi request reprint The nuclear receptors constitutive androstane receptor and pregnane X receptor cross-talk with hepatic nuclear factor 4alpha to synergistically activate the human CYP2C9 promoter
    Yuping Chen
    Human Metabolism Section, Laboratory of Pharmacology and Chemistry, National Institutes of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
    J Pharmacol Exp Ther 314:1125-33. 2005
    ....
  17. pmc Thr176 regulates the activity of the mouse nuclear receptor CAR and is conserved in the NR1I subfamily members PXR and VDR
    Akiko Ueda
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Biochem J 388:623-30. 2005
    ..Thr176, Thr248 and Ser230 are conserved residues in the NR1I (nuclear receptor 1I) subfamily members and determine their activity...
  18. ncbi request reprint Estrogen receptor alpha mediates 17alpha-ethynylestradiol causing hepatotoxicity
    Yukio Yamamoto
    Laboratories of Reproductive and Developmental Toxicology, NIEHS National Institutes of Health, Research Triangle Park, NC 27709, USA
    J Biol Chem 281:16625-31. 2006
    ..Taken together, these results suggest that ERalpha-mediated repression of hepatic transporters and alterations of bile acid biosynthesis may contribute to development of the EE2-induced hepatotoxicity...
  19. pmc Early growth response 1 loops the CYP2B6 promoter for synergistic activation by the distal and proximal nuclear receptors CAR and HNF4alpha
    Kaoru Inoue
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    FEBS Lett 583:2126-30. 2009
    ..Chromatin conformation capture 3C assays demonstrated that ERG1 may loop the distal PBREM towards the proximal OARE(KI) so that together, CAR and HNF4alpha synergistically activate the CYP2B6 promoter...
  20. pmc Relative activation of human pregnane X receptor versus constitutive androstane receptor defines distinct classes of CYP2B6 and CYP3A4 inducers
    Stephanie R Faucette
    Division of Molecular Pharmaceutics, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA
    J Pharmacol Exp Ther 320:72-80. 2007
    ..Our results demonstrate that CMZ, EFV, and NVP induce CYP2B6 and CYP3A4 preferentially through hCAR and that hCAR3 represents a sensitive tool for in vitro prediction of chemical-mediated human CAR activation...
  21. ncbi request reprint Phenobarbital induction of drug/steroid-metabolizing enzymes and nuclear receptor CAR
    Satoru Kakizaki
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Biochim Biophys Acta 1619:239-42. 2003
    ..However, PB induction of the synthase occurs in CAR-null mice, suggesting that CAR does not coordinate the heme synthesis for the induction of drug/steroid metabolism...
  22. doi request reprint Phenobarbital indirectly activates the constitutive active androstane receptor (CAR) by inhibition of epidermal growth factor receptor signaling
    Shingo Mutoh
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Sci Signal 6:ra31. 2013
    ..The findings demonstrated that the phenobarbital-induced mechanism of CAR dephosphorylation and activation is mediated through its direct interaction with and inhibition of EGFR...
  23. pmc Extracellular signal-regulated kinase is an endogenous signal retaining the nuclear constitutive active/androstane receptor (CAR) in the cytoplasm of mouse primary hepatocytes
    Chika Koike
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    Mol Pharmacol 71:1217-21. 2007
    ..These results are consistent with the conclusion that the HGF-dependent phosphorylation of ERK1/2 is the endogenous signal that sequesters CAR in the cytoplasm of mouse primary hepatocytes...
  24. ncbi request reprint Novel CAR-mediated mechanism for synergistic activation of two distinct elements within the human cytochrome P450 2B6 gene in HepG2 cells
    Karen Swales
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 280:3458-66. 2005
    ..This functional interaction between the two sites expands the current understanding of the mechanism of CAR-mediated inducible transcription...
  25. pmc Nuclear receptors CAR and PXR cross talk with FOXO1 to regulate genes that encode drug-metabolizing and gluconeogenic enzymes
    Susumu Kodama
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Mol Cell Biol 24:7931-40. 2004
    ..We conclude that FOXO1 and the nuclear receptors reciprocally coregulate their target genes, modulating both drug metabolism and gluconeogenesis...
  26. pmc The nuclear receptors constitutive active/androstane receptor and pregnane x receptor activate the Cyp2c55 gene in mouse liver
    Yoshihiro Konno
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    Drug Metab Dispos 38:1177-82. 2010
    ..Chronic PB treatment increased hepatic microsomal CYP2C55 protein and serum 19-HETE levels. These findings indicate that CAR and PXR may play a role in regulation of drug-induced synthesis of 19-HETE in the mouse...
  27. pmc The chondroitin polymerase K4CP and the molecular mechanism of selective bindings of donor substrates to two active sites
    Mack Sobhany
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 283:32328-33. 2008
    ..Alternation of these two specific bindings advances the polymerization reaction by K4CP...
  28. ncbi request reprint Induction of human CYP2C9 by rifampicin, hyperforin, and phenobarbital is mediated by the pregnane X receptor
    Yuping Chen
    Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
    J Pharmacol Exp Ther 308:495-501. 2004
    ..This is the first report to demonstrate that the nuclear receptor PXR mediates induction of CYP2C9 with rifampicin, phenobarbital, and hyperforin...
  29. ncbi request reprint Regulation of human CYP2C9 by the constitutive androstane receptor: discovery of a new distal binding site
    Stephen S Ferguson
    Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Mol Pharmacol 62:737-46. 2002
    ....
  30. pmc Human nuclear pregnane X receptor cross-talk with CREB to repress cAMP activation of the glucose-6-phosphatase gene
    Susumu Kodama
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Biochem J 407:373-81. 2007
    ..Thus drug activation of PXR can repress the transcriptional activity of CREB, down-regulating gluconeogenesis...
  31. ncbi request reprint Crystal structure of human cholesterol sulfotransferase (SULT2B1b) in the presence of pregnenolone and 3'-phosphoadenosine 5'-phosphate. Rationale for specificity differences between prototypical SULT2A1 and the SULT2BG1 isoforms
    Karen A Lee
    Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 278:44593-9. 2003
    ..In addition, the amino-terminal helix comprising residues Asp19 to Lys26, which determines the specificity difference between the SULT2B1 isoforms, becomes ordered upon pregnenolone binding, covering the substrate binding pocket...
  32. pmc Active ERK1/2 protein interacts with the phosphorylated nuclear constitutive active/androstane receptor (CAR; NR1I3), repressing dephosphorylation and sequestering CAR in the cytoplasm
    Makoto Osabe
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 286:35763-9. 2011
    ..The phosphorylation levels of Thr-38 of CAR decreased in U0126-treated Huh-7 cells. Thus, activated ERK1/2 interacts with CAR and represses dephosphorylation of Thr-38, providing a cell signal-regulated mechanism for CAR activation...
  33. ncbi request reprint The constitutive active/androstane receptor regulates phenytoin induction of Cyp2c29
    Jonathan P Jackson
    Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Mol Pharmacol 65:1397-404. 2004
    ....
  34. pmc Nuclear pregnane X receptor cross-talk with FoxA2 to mediate drug-induced regulation of lipid metabolism in fasting mouse liver
    Kouichi Nakamura
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 282:9768-76. 2007
    ..These results are consistent with the conclusion that PCN-activated PXR represses FoxA2-mediated transcription of Ctp1a and Hmgcs2 genes in fasting liver...
  35. ncbi request reprint Localization of the nuclear receptor CAR at the cell membrane of mouse liver
    Chika Koike
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    FEBS Lett 579:6733-6. 2005
    ..Levels of the cell membrane CAR increased after PB treatment. The CAR exists as a large approximately 160 kDa complex. Thus, CAR undergoes PB-induced translocation to the cell membrane, indicating that CAR may exert a non-genomic action...
  36. ncbi request reprint Crystal structure of beta 1,3-glucuronyltransferase I in complex with active donor substrate UDP-GlcUA
    Lars C Pedersen
    Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 277:21869-73. 2002
    ..This structure supports the in-line displacement reaction mechanism previously proposed. It also provides information on the essential amino acid residues that determine donor substrate specificity...
  37. pmc Nuclear receptor CAR requires early growth response 1 to activate the human cytochrome P450 2B6 gene
    Kaoru Inoue
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 283:10425-32. 2008
    ..Thus, synergy of drug activation and the stimulation of cellular signal are necessary for CAR to activate the CYP2B6 gene...
  38. ncbi request reprint Direct expression of fluorescent protein-tagged nuclear receptor CAR in mouse liver
    Tatsuya Sueyoshi
    Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    Methods Enzymol 357:205-13. 2002
  39. ncbi request reprint The role of the nuclear receptor CAR as a coordinate regulator of hepatic gene expression in defense against chemical toxicity
    Yukio Yamamoto
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Arch Biochem Biophys 409:207-11. 2003
    ..Here we describe diverse roles of CAR in hepatic gene expression with a particular focus on endogenous substances such as cholesterol, bilirubin, and steroid hormones...
  40. pmc Nuclear receptor CAR-regulated expression of the FAM84A gene during the development of mouse liver tumors
    Hiroki Kamino
    Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Int J Oncol 38:1511-20. 2011
    ....
  41. ncbi request reprint Cytoplasmic accumulation of the nuclear receptor CAR by a tetratricopeptide repeat protein in HepG2 cells
    Kaoru Kobayashi
    National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Mol Pharmacol 64:1069-75. 2003
    ..Thus, these results indicate that CCRP may be a component of the CAR-hsp90 complex and involved in retaining the receptor in the cytoplasm of both HepG2 cells and probably in vivo liver cells...
  42. ncbi request reprint The nuclear receptor constitutively active/androstane receptor regulates type 1 deiodinase and thyroid hormone activity in the regenerating mouse liver
    Eric S Tien
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
    J Pharmacol Exp Ther 320:307-13. 2007
    ..Subsequent treatment with PB decreases rT3 in a CAR-dependent manner through the up-regulation of the D1 gene...
  43. ncbi request reprint The roles of nuclear receptors CAR and PXR in hepatic energy metabolism
    Yoshihiro Konno
    The Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, North Carolina 27709, USA
    Drug Metab Pharmacokinet 23:8-13. 2008
    ..In addition, CAR modulates thyroid hormone activity by regulating type 1 deiodinase in the regenerating liver. Thus, CAR and PXR are now placed at the crossroad where both xenobiotics and endogenous stimuli co-regulate liver function...
  44. pmc Nuclear xenobiotic receptor pregnane X receptor locks corepressor silencing mediator for retinoid and thyroid hormone receptors (SMRT) onto the CYP24A1 promoter to attenuate vitamin D3 activation
    Yoshihiro Konno
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Mol Pharmacol 75:265-71. 2009
    ..PCN-dependent loss of mineral density is observed in the metaphyseal bones of only the Pxr(+/+) mice. This loss, however, does not correlate with the expression levels of the Cyp24a1 gene in these mice...
  45. doi request reprint Nuclear xenobiotic receptor PXR-null mouse exhibits hypophosphatemia and represses the Na/Pi-cotransporter SLC34A2
    Yoshihiro Konno
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, North Carolina 27709, USA
    Pharmacogenet Genomics 20:9-17. 2010
    ..Our present study aims to elucidate the inherited phenotype that correlates with the decreased BMD and to identify the PXR-regulated gene that may link with this phenotype...
  46. ncbi request reprint Two-step mechanism that determines the donor binding specificity of human UDP-N-acetylhexosaminyltransferase
    Mack Sobhany
    Pharmacogenetic Section, Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 280:23441-5. 2005
    ..enzyme complex into the bulk solvent followed by positioning of the donor into the binding site for the subsequent interactions with the enzyme...
  47. pmc Phosphorylation of serine 212 confers novel activity to human estrogen receptor α
    Sawako Shindo
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Steroids 77:448-53. 2012
    ....
  48. ncbi request reprint Structural analysis by X-ray crystallography and calorimetry of a haemagglutinin component (HA1) of the progenitor toxin from Clostridium botulinum
    Kaoru Inoue
    National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Microbiology 149:3361-70. 2003
    ..The D263A and N285A mutants lost the ability to bind carbohydrates containing galactose moieties, implicating these residues in carbohydrate binding...
  49. pmc The antiapoptotic factor growth arrest and DNA-damage-inducible 45 beta regulates the nuclear receptor constitutive active/androstane receptor-mediated transcription
    Yukio Yamamoto
    Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Drug Metab Dispos 36:1189-93. 2008
    ....
  50. ncbi request reprint Residue threonine 350 confers steroid hormone responsiveness to the mouse nuclear orphan receptor CAR
    Akiko Ueda
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    Mol Pharmacol 61:1284-8. 2002
    ..However, overexpression of SRC-1 counteracted progesterone to repress mCAR activity. Thus, threonine 350 seems to regulate hormone responsiveness of mCAR by interfering indirectly an interaction of the receptor with a coactivator...
  51. pmc The structural basis for a coordinated reaction catalyzed by a bifunctional glycosyltransferase in chondroitin biosynthesis
    Mack Sobhany
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 287:36022-8. 2012
    ....
  52. pmc Nuclear receptor CAR (NR1I3) is essential for DDC-induced liver injury and oval cell proliferation in mouse liver
    Yuichi Yamazaki
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA
    Lab Invest 91:1624-33. 2011
    ..Thus, CAR provides an excellent experimental model for further investigations into its roles in liver regeneration, as well as the development of diseases such as hepatocellular carcinoma...
  53. pmc CAR and PXR: the xenobiotic-sensing receptors
    Yoav E Timsit
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, 111 T W Alexander Drive, Research Triangle Park, NC 27709, USA
    Steroids 72:231-46. 2007
    ..In addition, the physiological roles of CAR and PXR will be reviewed, with discussion of interactions of CAR and PXR with endocrine signaling pathways...
  54. ncbi request reprint Identification of the nuclear receptor CAR:HSP90 complex in mouse liver and recruitment of protein phosphatase 2A in response to phenobarbital
    Kouichi Yoshinari
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    FEBS Lett 548:17-20. 2003
    ..This recruitment may lead CAR to translocate into the nucleus, consistent with the inhibitions of nuclear CAR accumulation in PB-induced mouse primary hepatocytes by okadaic acid as well as by geldanamycin...
  55. ncbi request reprint Identification of constitutive androstane receptor and glucocorticoid receptor binding sites in the CYP2C19 promoter
    Yuping Chen
    Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
    Mol Pharmacol 64:316-24. 2003
    ..This is the first study to identify nuclear receptor binding sites (CAR/PXR and GR) in the CYP2C19 promoter and to suggest that these receptors may up-regulate CYP2C19 constitutively and possibly its response to drugs...
  56. ncbi request reprint The orphan nuclear receptor constitutive active/androstane receptor is essential for liver tumor promotion by phenobarbital in mice
    Yukio Yamamoto
    Laboratories of Reproductive and Developmental Toxicology and Experimental Pathology, National Institute of Environmental Health Sciences, National Institutes of Health, Research TrianglePark, NC, USA
    Cancer Res 64:7197-200. 2004
    ..The results indicate that CAR is the molecular target of promotion by PB and that activation of this receptor is an essential requirement for liver tumor development...
  57. pmc p38 Mitogen-activated protein kinase regulates nuclear receptor CAR that activates the CYP2B6 gene
    Kosuke Saito
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA
    Drug Metab Dispos 41:1170-3. 2013
    ....
  58. ncbi request reprint Crystal structure of the human estrogen sulfotransferase-PAPS complex: evidence for catalytic role of Ser137 in the sulfuryl transfer reaction
    Lars C Pedersen
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 277:17928-32. 2002
    ..Thus, Ser(137) appears to play an important role in regulating the side chain interaction of Lys(47) with the bridging oxygen between the 5'-phosphate and the sulfate of PAPS...
  59. ncbi request reprint CAR, driving into the future
    Karen Swales
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    Mol Endocrinol 18:1589-98. 2004
    ..Although this mechanism remains under investigation, we have summarized here the cellular signaling pathways elucidated so far and speculate on the mechanism by which CAR activators regulate gene expression through this network...
  60. pmc Serum- and glucocorticoid-regulated kinase 2 determines drug-activated pregnane X receptor to induce gluconeogenesis in human liver cells
    Saki Gotoh
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina
    J Pharmacol Exp Ther 348:131-40. 2014
    ..Mediating PXR activation of the G6Pase gene is the first biological role found for hepatic SGK2 and might have therapeutic implications for side effects, such as diabetes, caused by drugs that activate PXR. ..
  61. pmc Role of a novel CAR-induced gene, TUBA8, in hepatocellular carcinoma cell lines
    Hiroki Kamino
    Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA
    Cancer Genet 204:382-91. 2011
    ....
  62. pmc Crystallographic analysis of a hydroxylated polychlorinated biphenyl (OH-PCB) bound to the catalytic estrogen binding site of human estrogen sulfotransferase
    Sergei Shevtsov
    Pharmacogenetic Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    Environ Health Perspect 111:884-8. 2003
    ..The crystal structure of hEST with the OH-PCB bound gives physical evidence that certain OH-PCBs can mimic binding of estrogenic compounds in biological systems...
  63. pmc Characterization of specific donor binding to alpha1,4-N-acetylhexosaminyltransferase EXTL2 using isothermal titration calorimetry
    Mack Sobhany
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC, USA
    Methods Enzymol 416:3-12. 2006
    ..This chapter describes our ITC study demonstrating the two-step mechanism that regulates the specific binding of N-acetylhexosamines to EXTL2...
  64. pmc Garlic extract diallyl sulfide (DAS) activates nuclear receptor CAR to induce the Sult1e1 gene in mouse liver
    Tatsuya Sueyoshi
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America
    PLoS ONE 6:e21229. 2011
    ..Despite the remarkable induction of SULT1E1, there was no decrease in the serum levels of endogenous E2 or increase of estrone sulfate while the clearance of exogenously administrated E2 was accelerated in DAS treated mice...
  65. ncbi request reprint The environmental pollutant 1,1-dichloro-2,2-bis (p-chlorophenyl)ethylene induces rat hepatic cytochrome P450 2B and 3A expression through the constitutive androstane receptor and pregnane X receptor
    Michael E Wyde
    CIIT Centers for Health Research, Research Triangle Park, North Carolina, USA
    Mol Pharmacol 64:474-81. 2003
    ..This study suggests that regulation by environmental compounds of hepatic enzymes via CAR and PXR may have impact on the metabolism of endogenous and exogenous substrates...
  66. pmc Inter-alpha-trypsin inhibitor promotes bronchial epithelial repair after injury through vitronectin binding
    Jennifer E Adair
    National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 284:16922-30. 2009
    ..We conclude that IaI interacts not only with hyaluronan, as previously reported, but also other ECM components like vitronectin and is an important regulator of cellular repair after injury...
  67. pmc Nuclear receptor CAR specifically activates the two-pore K+ channel Kcnk1 gene in male mouse livers, which attenuates phenobarbital-induced hepatic hyperplasia
    Kosuke Saito
    National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Toxicol Sci 132:151-61. 2013
    ..Thus, KCNK1 and Kcnk1 ( -/- ) mice provide an experimental tool for further investigation into the molecular mechanism of CAR-mediated promotion of the development of hepatocellular carcinoma in mice...
  68. pmc The nuclear receptor constitutive active/androstane receptor arrests DNA-damaged human hepatocellular carcinoma Huh7 cells at the G2/M phase
    Hiroki Kamino
    Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    Mol Carcinog 51:206-12. 2012
    ..Thus, the results suggest that CAR regulates cell cycle, increasing G2/M arrest, and delaying the death of DNA-damaged cells...
  69. ncbi request reprint Phenobarbital confers its diverse effects by activating the orphan nuclear receptor car
    Susumu Kodama
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Drug Metab Rev 38:75-87. 2006
    ..Upon activation by PB and numerous PB-type inducers, the nuclear receptor CAR mediates those pleiotropic actions by regulating various hepatic genes, utilizing multiple regulatory mechanisms...
  70. ncbi request reprint Diverse roles of the nuclear orphan receptor CAR in regulating hepatic genes in response to phenobarbital
    Akiko Ueda
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    Mol Pharmacol 61:1-6. 2002
    ..Thus, CAR seems to have diverse roles, both as a positive and negative regulator, in the regulation of hepatic genes in response to PB beyond drug/steroid metabolism...
  71. ncbi request reprint Retinoic acids repress constitutive active receptor-mediated induction by 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene of the CYP2B10 gene in mouse primary hepatocytes
    Satoru Kakizaki
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    Drug Metab Dispos 30:208-11. 2002
    ..This type of nuclear receptor signaling may play an important role as a modulator in the CYP2B regulation...
  72. pmc Pregnane X receptor PXR activates the GADD45beta gene, eliciting the p38 MAPK signal and cell migration
    Susumu Kodama
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 286:3570-8. 2011
    ..The GADD45β gene is a direct target for PXR, eliciting cell signals to regulate various cellular functions...
  73. ncbi request reprint Crystal structure-based studies of cytosolic sulfotransferase
    K Yoshinari
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    J Biochem Mol Toxicol 15:67-75. 2001
    ..These crystal structures introduce a new era of the study of the sulfotransferases...
  74. ncbi request reprint Heparan sulphate N-sulphotransferase activity: reaction mechanism and substrate recognition
    Y Kakuta
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, U S A
    Biochem Soc Trans 31:331-4. 2003
    ..Glu-642 may play the critical role of catalytic base in the sulphuryl group transfer reaction, as indicated by its hydrogen-bonding distance to the NH(3) (+) group of the glucosamine moiety in the model and by mutational data...
  75. ncbi request reprint A role of Lys614 in the sulfotransferase activity of human heparan sulfate N-deacetylase/N-sulfotransferase
    T Sueyoshi
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    FEBS Lett 433:211-4. 1998
    ..Crystals of the ST domain have been grown (orthorhombic space group P2(1)2(1)2) with diffraction to 2.5 A resolution...
  76. pmc Structural alteration of mouse P450coh by mutation of glycine-207 to proline: spin equilibrium, enzyme kinetics, and heat sensitivity
    R O Juvonen
    Pharmacogenetics Section, National Institutes of Health, Research Triangle Park, NC 27709
    Biochem J 294:31-4. 1993
    ..A Gly-207 to Pro mutation, therefore, results in the creation of a larger substrate pocket in the mutant cytochrome P-450 by altering the protein structure around residue 209 so that a water molecule and testosterone can be accommodated...
  77. ncbi request reprint Crystal structure of the sulfotransferase domain of human heparan sulfate N-deacetylase/ N-sulfotransferase 1
    Y Kakuta
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 274:10673-6. 1999
    ..The conserved residue Lys-614 is in position to form a hydrogen bond with the bridge oxygen of the 5'-phosphate...
  78. ncbi request reprint Crystal structure of SULT2A3, human hydroxysteroid sulfotransferase
    L C Pedersen
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    FEBS Lett 475:61-4. 2000
    ..Moreover, protein interaction in the crystal structure has revealed a possible dimer-directed conformational alteration that may regulate the SULT activity...
  79. ncbi request reprint Characterization and regulation of sex-specific mouse steroid hydroxylase genes
    H Yoshioka
    Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709
    Can J Physiol Pharmacol 68:754-61. 1990
    ..It appears, therefore, that the mouse P-450 gene families evolved through gene duplication and selective mutation to create new P-450s structurally as well as to establish novel regulatory elements for the gene expressions...
  80. ncbi request reprint Molecular characterization of a testis-specific estrogen sulfotransferase and aberrant liver expression in obese and diabetogenic C57BL/KsJ-db/db mice
    W C Song
    Pharmacogenetics Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    Endocrinology 136:2477-84. 1995
    ..These results recapitulate the species-specific nature in the tissue distribution of estrogen sulfotransferase and suggest complex regulatory mechanisms in its expression under normal and pathophysiological conditions...
  81. ncbi request reprint Heparan/chondroitin sulfate biosynthesis. Structure and mechanism of human glucuronyltransferase I
    L C Pedersen
    Pharmacogenetic Section, Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 275:34580-5. 2000
    ..The key residues involved in substrate binding and catalysis are conserved in the glucuronyltransferase family as well as other glycosyltransferases...
  82. ncbi request reprint The dimerization motif of cytosolic sulfotransferases
    E V Petrotchenko
    Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, NIEHS NIH, Research Triangle Park, NC 27709, USA
    FEBS Lett 490:39-43. 2001
    ..Thus, the KXXXTVXXXE sequence appears to be the common protein-protein interaction motif that mediates the homo- as well as heterodimerization of cytosolic sulfotransferases...
  83. ncbi request reprint The structure and characterization of type I P-450(15) alpha gene as major steroid 15 alpha-hydroxylase and its comparison with type II P-450(15) alpha gene
    R Lindberg
    Pharmacogenetics Section, National Institute of Environmental Health Sciences, Triangle Park, North Carolina 27709
    J Biol Chem 264:6465-71. 1989
    ..The results indicated that Type I was the major steroid 15 alpha-hydroxylase. The differential 15 alpha OH-1 expression, therefore, determined the sexual dimorphism of the tissue-specific 15 alpha-hydroxylase activity in mice...
  84. ncbi request reprint Alteration of mouse cytochrome P450coh substrate specificity by mutation of a single amino-acid residue
    R L Lindberg
    Pharmacogenetics Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
    Nature 339:632-4. 1989
    ....
  85. pmc Site-directed mutagenesis of mouse steroid 7 alpha-hydroxylase (cytochrome P-450(7) alpha): role of residue-209 in determining steroid-cytochrome P-450 interaction
    M Iwasaki
    Pharmacogenetics Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709
    Biochem J 291:569-73. 1993
    ..The results indicate, therefore, that the identity of residue 209 determines the affinity as well as specificity of steroid binding to both P450(7) alpha and P450(15) alpha...
  86. ncbi request reprint The structure, function, and regulation of cytochrome P450 2A enzymes
    P Honkakoski
    Pharmacogenetics Section, National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Drug Metab Rev 29:977-96. 1997
  87. ncbi request reprint Transcriptional regulation of cytochrome p450 2B genes by nuclear receptors
    Hongbing Wang
    School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Curr Drug Metab 4:515-25. 2003
    ..These findings should provide greater insight into the mechanisms and species-specific differences of CAR regulation of CYP2B and other target genes...
  88. ncbi request reprint Regulation of CYP2B6 in primary human hepatocytes by prototypical inducers
    Stephanie R Faucette
    Division of Drug Delivery and Disposition, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7360, USA
    Drug Metab Dispos 32:348-58. 2004
    ..These results indicate that CYP2B6 is highly inducible by known CYP3A4 inducers and suggest that hPXR is a major determinant of CYP2B6-inducible expression for many, but not all, compounds evaluated in this study...
  89. doi request reprint Expression of CAR in SW480 and HepG2 cells during G1 is associated with cell proliferation
    Makoto Osabe
    Department of Pharmaco Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52 1 Yada, Suruga ku, Shizuoka 422 8526, Japan
    Biochem Biophys Res Commun 369:1027-33. 2008
    ....
  90. pmc Regulation of Cyp2a5 transcription in mouse primary hepatocytes: roles of hepatocyte nuclear factor 4 and nuclear factor I
    Johanna Ulvila
    Department of Pharmacology and Toxicology, University of Oulu, P O Box 5000, 90014 Oulu, Finland
    Biochem J 381:887-94. 2004
    ..In conclusion, these results indicate that HNF-4 and NF-I play major roles in the constitutive regulation of hepatic expression of Cyp2a5...
  91. ncbi request reprint Human constitutive androstane receptor mediates induction of CYP2B6 gene expression by phenytoin
    Hongbing Wang
    Division of Drug Delivery and Disposition, School of Pharmacy, University of North Carolina at Chapel Hill, North Carolina 27599, USA
    J Biol Chem 279:29295-301. 2004
    ..Taken together, these observations demonstrate that, in contrast to most of the known CYP2B6 inducers, PHY is a selective activator of CAR in humans...
  92. ncbi request reprint Transcriptional regulation of human UGT1A1 gene expression: activated glucocorticoid receptor enhances constitutive androstane receptor/pregnane X receptor-mediated UDP-glucuronosyltransferase 1A1 regulation with glucocorticoid receptor-interacting protei
    Junko Sugatani
    Department of Pharmaco Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52 1 Yada, Shizuoka 422 8526, Japan
    Mol Pharmacol 67:845-55. 2005
    ....
  93. ncbi request reprint A novel distal enhancer module regulated by pregnane X receptor/constitutive androstane receptor is essential for the maximal induction of CYP2B6 gene expression
    Hongbing Wang
    Division of Drug Delivery and Disposition, School of Pharmacy, University of North Carolina, Chapel Hill 27599, USA
    J Biol Chem 278:14146-52. 2003
    ..These results show that a novel xenobiotic-responsive enhancer module in the distal region of the CYP2B6 promoter (CYP2B6-XREM) together with the PBREM mediates optimal drug-induced expression of CYP2B6...
  94. ncbi request reprint Differential UGT1A1 induction by chrysin in primary human hepatocytes and HepG2 Cells
    Cornelia M Smith
    Division of Drug Delivery and Disposition, School of Pharmacy, CB 7360, Kerr Hall, Room 2319, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7360, USA
    J Pharmacol Exp Ther 315:1256-64. 2005
    ..In conclusion, this study suggests that the metabolic stability of chrysin likely would limit its ability to induce UGT1A1 in vivo...
  95. pmc Explicit water near the catalytic I helix Thr in the predicted solution structure of CYP2A4
    Anna Gorokhov
    Department of Chemistry, University of North Carolina, Chapel Hill, 27599, USA
    Biophys J 84:57-68. 2003
    ..The properties of the I helix are computed in the context of the presence or absence of ligand...
  96. ncbi request reprint Regulation of the human UGT1A1 gene by nuclear receptors constitutive active/androstane receptor, pregnane X receptor, and glucocorticoid receptor
    Junko Sugatani
    Department of Pharmaco Biochemistry and 21 COE, School of Pharmaceutical Sciences, University of Shizuoka, Japan
    Methods Enzymol 400:92-104. 2005
    ....
  97. ncbi request reprint Differential regulation of hepatic CYP2B6 and CYP3A4 genes by constitutive androstane receptor but not pregnane X receptor
    Stephanie R Faucette
    Division of Molecular Pharmaceutics, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7360, USA
    J Pharmacol Exp Ther 317:1200-9. 2006
    ....
  98. ncbi request reprint Role of constitutive androstane receptor in the in vivo induction of Mrp3 and CYP2B1/2 by phenobarbital
    Hao Xiong
    Division of Drug Delivery and Disposition, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599 7360, USA
    Drug Metab Dispos 30:918-23. 2002
    ..Interestingly, differences in the constitutive levels of Mrp3 were observed between obese and lean Zucker rats and between male and female WKY rats...
  99. ncbi request reprint The human sulfotransferase SULT1A1 gene is regulated in a synergistic manner by Sp1 and GA binding protein
    Nadine Hempel
    Department of Physiology and Pharmacology, School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia
    Mol Pharmacol 66:1690-701. 2004
    ....
  100. ncbi request reprint Drug-activated nuclear receptors CAR and PXR
    Paavo Honkakoski
    Department of Pharmaceutics, University of Kuopio, P O Box 1627, FIN 70211 Kuopio, Finland
    Ann Med 35:172-82. 2003
    ..This review outlines the basic properties of CAR and PXR, their ligands and target genes, and the mechanisms of the induction process. The implications of nuclear receptor-mediated induction for drug research are also discussed...
  101. pmc The role of the nuclear receptor constitutive androstane receptor in the pathogenesis of non-alcoholic steatohepatitis
    Yuichi Yamazaki
    Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
    Gut 56:565-74. 2007
    ..The pathological roles of the nuclear receptor constitutive androstane receptor (CAR), a key regulator of drug-metabolising enzymes, in the development of NASH were investigated...