固醇调节元件结合蛋白1c在肝脂肪合成中转录调节

-1c兰英,王继文*,曾兵,许恒勇,卓伟华(,625014)固醇调节元件结合蛋白-1c(SREBP-1c)是脂肪合成基因的重要转录调节因子,又称脂肪细胞决定和分化因子1(AdipocyteDeterm-inationandDifferentiationfactor1,ADD1),它是动物肝脏中主要的转录物,主要调节动物脂肪合成和葡萄糖代谢相关基因的表达研究发现,SREBP-1c的过度表达与肝脏等非脂肪组织的脂质积聚相关SREBP-1c调节体内的脂肪合成主要是通过改变自身的mRNA水平来实现的,即生脂酶的转录调节是由SREBP-1cmRNA的数量控制的另一方面,LXRs胰岛素胰高血糖素等因素对SREBP-1c的转录有调节作用固醇调节元件结合蛋白-1c;脂肪肝;转录调节S549A0517-6611(2005)03-0499-03AdvancedResearchofSREBP-1cTranscriptionalRegulationinFattyLiverFormationLANYingetal(CollegeofAnimalScienceandTechnology,SichuanAgriculturalUniversity,Yaan,Sichuan625014)AbstractSterolregulatoryelemen-tbindingprotein-1c(SREBP-1c),alsocalledAdipocyteDeterminationandDifferentiationfactor1(ADD1),isimportanttranscriptionalregulationoflipidsyntheticgenes.Itisthemajortranscriptsofliver,anditsmajorroleistheregulationofgenethatrelatedwithlipidsyn-thesisandglucosemetabolism.Iftheamountoffatinliverwasover5%ofthenewliverormorethan50%hepatocytesbecominglipocytes,theliverwasconsideredasfattyliver.Theover-expressionofSREBP-1cwascorrelatedwiththeaccumulationoffatintheliver.TranscriptionalregulationoflipogenicenzymeswascontrolledbytheamountofSREBP-1cmRNA.Ontheotherhand,liverXreceptors(LXRs),insulinandglucagonsaffectedthetranscriptionofSREBP-1c.KeywordsSREBP-1c;Fattyliver;Transcriptionalregulation(SREBP),/---0(basichelix-loop-helix-leucine-Zipper,bHLH-Zip)SREBP3:SREBP-1aSREBP-1cSREBP-2SREBP-1aSREBP-1cSREBP-1,SREBP-2SREBP-2SREBP-1c90%SREBP-1,[1]SREBP-1c1(ADD1),,,SREBP-1c,,[2]SREBP-1c,(),Ò1SREBP-1c1.1SREBP-1cSREBP-1c17p11.2[3],AssafSREBP-114[4]SREBP-1mRNA4154bp[5]1.2SREBP-1cSREBP-1c1150,3:,480;2,80;,590[6],2,312,SREBP-1cbHLH-Zip,兰英(1978-),女,四川岳池人,硕士研究生,从事动物遗传育种与繁殖研究*通讯作者,副教授,E-mail:[e-mail]2004-12-13bHLH-Zip,DNASREBP-1cbHLH-Zip,,SREBP-1c(SRE)[7]1.3SREBP-1cSREBP-1c125kDa,47068kDaSREBP-1cSREBP-1c(nSREBP-1c),1(S1P)2(S2P)2,bHLH-ZipnSREBP-1c[8]SREBP-1cS1P,SREBP(SCAP)SCAP,SREBP-1c,SREBP-1c,;,SCAPSREBP-1c,SREBP-1c2,SREBP-1cbHLH,SRE,[7]2SREBP-1c2.1SREBP-1cSRESREBP-1c-90bpY(NF-Y)E-SRESp1(1)[9],SRE,LXR/RXR(LXR:X,RXR:XAX)SRE,[10],SREBP-1c,,,SREBP-1cmRNA,JournalofAnhuiAgri.Sci.2005,33(3):499-501,509孙红忠孙红忠[11]2.2SREBP-1cLXR/RXRLXRRXRSREBP-1c,nSREBP-1c,SREBP-1c,SRE(SREelements)2setATP(ABC1)LXR(LXRE)[12]RepaLXR/RXRSREBP-1c,LXR/RXRnSREBP-1c,[13]YoshikawaLXRALXRBSREBP-1c[14]HitoshiLXR,,[10]Guoxun,SREBP-1cLXRs,LXRsRXRs[15]SREBP-1c,SREBP-1c,,,,SREBP-1c,3SREBP-1cSREBP-1c,SREBP-1cSREBP-1c[16]SREBP-1c,(),SREBP-1c3.1SREBP-1cSREBP-1c,,[17]SREBP-1cmRNA,SREBP-1cmRNASREBP-1c:(LDLR),A(ACC),(FAS),S14,(GK)(PEPCK)[18],SREBP-1c,3.2SREBP-1cRosalind,SREBP-1cLXRsSREBP-1cSRE,nSREBP-1c[19]3:LXRsSREBP-1c[16]3.2.1LXRSREBP-1cLXR,cDNALXRLXRALXRB,77%,[20]3.2.1.1LXRALXRBSREBP-1cLXRALXRB,SREBP-1cLXRSREBP-1c,SREBP-1c,SREBP-1c,nSREBP-1c,SREBP-1cLXR,LXRALXRBSREBP-1c[13],LXRSREBP-1c,SREBP-1c,LXRSREBP-1c,[21]LXRABRXRLXR/RXRLXR/RXRSREBP-1cLXRE,SREBP-1c,[22]SREBP-1cLXRLXRSREBP-1c[13]LXRSREBP-1c2LXRALXRBSREBP-1c,SREBP-1c,LXRSREBP-1c[23]LXRSREBP-1c,,3.2.1.2(PUFA)SREBP-1cLXRSREBP-1c,SREBP-1c,[16]PU-FASREBP-1cmRNA,ACCFASCoAÑ(SCD-1)ATPmtGPAT[24]PUFASREBP-1c[25]Xu,SREBP-1cmRNA[21]SREBP-1cmRNA,SREBP-1c,[26]LXRSREBP-1cLXR(),LXR,SREBP-1cLXR[27]SREBP-1c[27]CoALXRLXR,mRNASREBP-1c[28],SREBP-1cmRNASREBP-1c3.2.2/SREBP-1c3,,,SREBP-1c,SREBP-1cSREBP-1c500安徽农业科学2005,Guoxun,SREBP-1c[15],SREBP-1c,-(cAMP)[29],cAMP,SREBP-1c,SREBP-1cmRNAmRNA[30]SREBP-1c(dominantnegative),,[30],cAMPSREBP-1cmRNAmRNA[31],SREBP-1c(/)(/)[9]SREBP-1cmRNASREBP-1c,SREBP-1cmRNA,,,SREBP-1cmRNA[30]nSREBP-1cmRNA[32]nSREBP-1c,[23],SREBP-1c,3.2.3SREBP-1c,HastyH2-35,SREBP-1cSREBP-1c,SREBP-1c[32]BMin6B[33]Koo,SREBP-1c;SREBP-1c,(ChREBP),,[34],SREBP-1c(),,4SREBP-1c:,,SREBP-1c,SREBP-1c,,,SREBP-1c,SREBP-1c,SREBP-1c,1OsborneTF.Sterolregulatoryelemen-tbindingproteins:keyregulatorsofnu-tr-itionalhomeostasisandinsulinaction[J].JBiolChem,2000,275:32379-32382.2童国玉,李果.固醇调节元件结合蛋白1c的研究进展[J].国外医学内分泌学分册,2002,22(5):328-331.3HuaX,WuJ,GoldsteinJL,etal.Structureofthehumangeneencodingsterolreg-ulatoryelementbindingprotein-1(SREBP1)andlocalizationofSREBP-1andSREBP-2tochromosomes17p11.2and22q13[J].Genomics,1995,25(3):667-673.4AssafS,HazardD,PitelF,etal.CloningofcDNAencodingthenuclearformofchickensterolresponseelementbindingprotein-2(SREBP-2),chromosomallo-calization,andtissueexpressionofchickenSREBP-1and-2Genes[J].PoultryScience,2003,82:54-61.5ShimanoH,ShimomuraaI,HammerRE,etal.ElevatedlevelsofSREBP-2andcholesterolsynthesisinliversofmicehomozygousforatargeteddisruptionoftheSREBP-1gene[J].JClinInvest,1997,100(8):2115-2124.6BrownMS,GoldsteinJL.TheSREBPpathway:Regulationofcholesterolmet-bolismbyproteolysismembrane-bondtranscriptionalfactor[J].Cell,1997,89:331-340.7柴红燕,刘芳,周新.固醇调节元件结合蛋白的研究[J].生命的化学,2002,22(5):442-444.8SakaiJ,DuncanEA,RawsonRB,etal.Stero-lregulatedreleaseofSREBP-2fromcellmembranesrequirestwosequentialcleavages,onewithinatransmem-branesegment[J].Cell,1996,85(7):1037-1046.9HortonJD,BashmakovY,ShimomuraI,etal.Regulationofsterolregulatoryele-mentbindingproteinsinliversoffastedandrefedmice[J].ProcNatlAcadSci,1998,95(11):5987-5992.10HitoshiShimano.Sterolregulatoryelemen-tbindingp