中国临床药理学与治疗学(6)

CN3421206PR,ISSN100922501E2mail:[e-mail]2007Sep;12(9):974-97920072032262007206204,,,Tel:[phone]E2mail:[e-mail],,,,Tel:[phone]E2mail:[e-mail],,410078,(UDP2glucuro2nosyltransferase,UGT),,X(pregnaneXreceptor,PXR)(constitutiveandrostanere2ceptor,CAR)(orphannuclearreceptors)UGT,UGT,(NR)UGTUGT,;;:R969;R968:A:100922501(2007)0920974206(UDP2glucuro2nosyltransferase,UGTs),,,UGT,;;UGTCYP450,,,UGT117,4,UGT1UGT2UGT3UGT8[1]X(preg2naneXreceptor,PXR)(constitu2tiveandrostanereceptor,CAR)(peroxisomeproliferatorsactivatedreceptor,PPAR);,(oxysterols)X(RXR),UGT1UGTUGT1237,200kbmRNA,34(225),1,5113,2259UGT1,1,PUGT14,UGT1,(UDPGA)UGT1479,UGT1UGT2413,6UGT2UGT2AUGT2BUGT2AUGT2A12A2UGT2A33;UGT2B75,2[2]PUGT2UGT1,UGT2A12A25,,UGT3,,UGT3A1UGT3A2UGT3513,7,76kb,UGT3UGT1UGT2UGT830%UGT3,UGT8,426,5UGT8[1]1UGT12UGT22PXRCARPPARPXRCARPPAR,PXR[3],3,hPXR(T1)hPXR(T2)hPXR(T3)T1PXR,T2T1N239,T3T137PXR,PXR,RXR(X),[4]RXR,[5],CAR,,CARPXR,RXR,PXR[6]PPARPPARPPAR(PPAR)PPAR3PPAR,PPARPPARJ2PPAR,[7]3PXRCARPPARUGT3.1PXRUGTUGT3:(1),;(2);(3)UGT(xenobioticresponseelements,XRE)PXRUGT,ChenUGTPCN(PXR)UGTPCNUGT,PXR;PCNUGT1A11A9mRNA,UGT1A21A62B5mRNA,PXRChenUGT1A31A41A6UGT1A9hPXR,UGT2BPXR[8]JunkoSugataniPXRUGT,,,UGT1A15792007Sep;12(9)PXR,GGTTCATA2AAGGGTA(EMSA)CARPXRUGT1A1,UGT1A1,PXRCARUGT1A1,PXRCARUGT[9]PXRUGT1A,UGT2B12B12[10]ChenUGT2BhPXR,PXRUGT1A1PXR,UsuiUGT1A1PXR[11],PXRhPXR3,Gardner2Ste2phenhPXRUGTHepG2Caco22,T1T2UGT1A,UGT2B,T3PXRUGT1A,HepG2UGT1A6,Caco22[12]ShelbPXRUGT[10],PXRUGTPXRUGT[13]PXR()CARUGT,UGT,,PXR,3.2CARUGTPXR,CRARXR,(PBREMs)CAR,4AGTTCA[14]PXRCAR,PXRCARUGT1A1DR3UGT1A1,LehmannJM,hPXRCAR[3]2006ShelbCARUGT1A,UGT1A11A51A6;,UGT2B1UGT2B12CARUGT,UGT1A11A5UGT2B1PXRCAR,CARUGTPXR[10],CARCAR,CAR,,JunkoSugataniPXRCARUGT1A1(GR)(DEX),GRUGT1A1,DEXPXRCARUGT1A1HepG2,DEXPXRPCARUGT1A1,GR(+)GR(2),DEXGR,EMSAUGT1A1DR3GR[9]3.3PPARUGT,PPAR,UGT2003UGT1A9PPARPPARPPARPPAR,3UGT1A9,PPARUGT1A9mRNAEMSA,UGT1A9-719706PPAR(PPREs),[15],PPREsAGGTCA,PXRCAR,PPARRXR[16]UGT2B4PPARPPARUGT2B4,PPAREMSAPPARUGT2B42119321180bp[15],PPARUGT1A11A31A5[10],679ChinJClinPharmacolTher2007Sep;12(9)1995[17]2007Senekeo2Effen2bergerUGT1A,PPARWY14643UGT1A11A31A4UGT1A6,UGT1A11A31A6PPAR[18],PPARUGT1A3.4UGTX(LXR),[19];,[20,21]LXRLXRLXR,77%,RXR[19]X(FXR),[22]LXRFXRUGT2006VerreaultUGT1A,LXRUGT1A3,UGT1A3LXR(LXRE)[23]2005Caco22,hFXRUGT2B7,EMSAhFXRUGT2B721482134bp[24],21(HNF21)()(AhR)Nrf2[nuclearfactorerythroid2(NF2E2)2relatedfactor2]UGTHNF21,HNF21HNF21HNF21,HNF21[25,26],HNF21UGT,UGT1A11A72B74B4,HNF21[2729]AhRhelix2loop2helixPAS(PER2ARNT2SIM)AhRCYP450,UGT,UGT1A11A6,UGT1A1AhRTGCGTG[6]Nrf2AhR,Nrf2UGT1AUGT2B[30]AhRNrf2,Nrf2AhR,,UGT1A61A7[10],CAAT2(CAAT2enhancerbindingprotein)21(OctamerTran2scriptionFactor21)Pbx2,UGT,,UGT[6]4,,,,,,,UGT,PXRCARPPAR,,UGT,PXRUGT2B7,UGT,1MackenziePI,OwensIS,BurchellB,etal.TheUDPglyco2syltransferasegenesuperfamily:recommendednomenclatureup2datebasedonevolutionarydivergence[J].Pharmacogenetics,1997;7:255-269.2MackenzieaPI,BockbKW,BurchellcB,etal.NomenclatureupdateforthemammalianUDP2glycosyltransferase(UGT)genesuperfamily[J].PharmacogenetGenomics,2005;15:677-685.3LehmannJM,MckeeDD,WatsonMA,etal.Thehumanor2phannuclearreceptorPXRisactivatedbycompoundsthatregu2lateCYP3A4geneexpressionandcausedruginteractions[J].JClinInvest,1998;102:1016-1023.4XuCJ,ChristinaLiYT,Ah2NgTK.InductionofPhaseI,IIandIIIDrugMetabolismPTransportbyXenobiotics[J].ArchPharmRes,2005;28:249-268.5ChambonP.Adecadeofmolecularbiologyofretinoicacidre2ceptors[J].FASEBJ,1996;10:940-954.6ZhouJ,ZhangJ,XieW.Xenobioticnuclearreceptor2mediated7792007Sep;12(9)regulationofUDP2glucuronosyltransferases[J].CurrDrugMetab,2005;6:289-298.7ChinettiG,LestavelS,BocherV,etal.PPAR2[alpha]andPPAR2[gamma]activatorsinducecholesterolremovalfromhu2manmacrophagefoamcellsthroughstimulationoftheABCA1pathway[J].NatMed,2001;7:53-58.8ChenC,StaudingerJL,KlaassenCD.Nuclearreceptor,preg2nameXreceptor,isrequiredforinductionofUDP2glucuronosyl2tranferasesinmouseliverbypregnenolone216alpha2carbonitrile[J].DrugMetabDispos,2003;31:908-915.9JunkoS,ShinichiN,KasumiY,etal.Transcriptionalregula2tionofhumanUGT1A1geneexpression:activatedglucocorticoidreceptorenhancesconstitutiveandrostanereceptorPpregnaneXreceptor2mediatedUDP2glucuronosyltransferase1A1regulationwithglucocorticoidreceptor2interactingprotein1[J].MolPhar2macol,2005;67:845-855.10ShelbyMK,KlaassenCD.InductionofratUDP2glucuronosyl2transferasesinliverandduodenumbymicrosomalenzymein2ducersthatactivatevarioustranscriptionalpathways[J].DrugMetabDispos,2006;34:1772-1778.11UsuiT,KunoT,MizutaniT.InductionofhumanUDP2glucu2ronosyltransferase1A1bycortisol2GR[J].MolBiolRep,2006;33:91-96.12Gardner2StephenD,HeydelJM,GoyalA,etal.HumanPXRvariantsandtheirdifferentialeffectsontheregulationofhumanUDP2glucuronosyltransferasegeneexpression[J].DrugMetabDispos,2004;32:340-347.13HeydelJ,LeclercS,BernardP,etal.RatolfactorybulbandepitheliumUDP2glucuronosyltransferase2A1(UGT2A1)ex2pression:insitumRNAlocalizationandquantitativeanalysis[J].BrainResMolBrainRes,2001;90:83-92.14JunkoS,TatsuyaS,MasahikoN,etal.Regulationofthe