ACE2在SARS发病中作用的研究进展

20086163ACTALABORATORIUMANIMALISSCIENTIASINICAJune,2008Vol.16No.3ACE2SARS陈云新,秦川(,,100021)=(SARS)SARS(SARS-CoV),SARS-CoV2(ACE2),ACE2SARS-CoVACE2,ACE2SARSACE2SARSSARS-CoVACE2ACE2SARS=;2;=R37311=1005-4847(2008)03=1005-4847(2008)03-0229-04ProgressinResearchontheRoleofACE2inSARSPathogenesisCHENYun-xin,QINChuan(InstituteofLaboratoryAnimalScience,ChineseAcademyofMedicalScienceandPekingUnionMedicalCollege,Beijing100021,China)=AbstractSevereacuterespiratorysyndrome(SARS)isanemerginginfectiousdiseasecausedbyanovelcoronavirus(CoV)variant,SARS-CoV.Withinseveralmonths,newinformationshavebeenpublicated,amongothers,theSARS-CoVgenome,angiotensin-convertingenzyme2(ACE2)wasidentifiedasthereceptorforSARS-CoV.Studiesshowedthatthevirusreceptorsmayplayakeyroleintheentryofthepathogenintothehostcells.SoitisnecessarytoinvestigatetherelationshipbetweenSARS-CoVandACE21ThispaperfirstlyreviewedthedistributionandfunctionofACE2proteininvariousorgansinhumans.ThenwesummarizedtherelationshipbetweenACE2variationwithSARS-CoVentryandSARSseverity.TherelationshipbetweenACE2expressionwithSARS-CoVentryandSARSseveritywasalsoincluded.ThesestudieswillprovideatheoreticalbasisforunderstandingtheinteractionbetweentheSARS-CoVandACE2anddesigningnewdrugstargetingACE2receptor.=KeywordsSevereacuterespiratorysyndrome;Angiotensin-convertingenzyme2;Coronavirus[]NIH(R01HL080211-01)[](1979-),,:[],,,E-mail:[e-mail](severeacuterespiratorysyndrome,SARS)2002,200352233SARS,,10%20034,SARS(severeacuterespiratorysyndrome-coronavirus,SARS-CoV)[1-3],SARS,[4,5]SARS-CoVSARS,Li[6]SARS-2(ACE2),,ACE2SARSACE2SARS1ACE2ACE2X,18,805Ñ,N42CACE2,2:ACENcollectinC,ACE2ACE2SARS-CoVII(angiopoietinII,AngII)(des-arg-bradykinin)(neurotensin)(kinetensin)[7],,1,ACE[7,8],(angiotensinconvertingenzyme,ACE)ACE2,,ACEI(angiotensinconvertingenzyme,AngI),2,,ACE2ACE,SARS-CoVLi[6]SARS-CoVVeroE6,SARS-CoVSS1ACE2S1VeroE6,ACE2293TSSARS-CoVACE2293T,ACE2ACE2SARS-CoV,SARS-CoVMoore[9]ACE2SARS,ACE22ACE2ACE2,Ren[10](Caco-2)(Calu-3)VeroE6ACE2,ACE2,ACE2,SARS-CoVS,S,SARS-CoVACE2,Jia[11]ACE2,SARS-CoVACE2,,ACE2;,SARS-CoVACE,ACE2Harmer[12]Rea-ltimePCR72ACE2,ACE2,,ACE2,[13],ACE2[1,7,12],SARS-CoVACE2SARS-CoV,:ACE2,ACE2SARS,ACE2,,3ACE2SARS311ACE2SARSSARS,SARSSARSSARSACE2,Li[14]SSIVACE2293T,ACE2ACE2,ACE23T3,ACE2SARSACE2SARS-CoV,Li[15]ACE2S:Q24T27K3123020086163ActaLabAnimSciSin,June,2008,Vol.16,No.3H34E37D38Y41Q42L45L79M82Y83N90Q325E329N330K353G354LiACE2S,ACE2,Holmes[16]ACE2M82NK353H,82353,M82SK353H,ACE2G354QACE2Han[17]22-57SARS-CoV,K26D30,,,,,312ACE2SARSHIVCCR5-D32HIV-1,AIDS[18]Ò,[19],SARS-CoV,ACE2SARSChiu[20]168SARS,SNP,ACE2103SNP,SARSItoyama[21]44SARS103ACE2,ACE2SARSACE2SARS4ACE2SARS411ACE2SARSACE2SARSMossel[22]30SARS-CoV,SARS-CoV6:3(VeroVeroE6MA104)(CaCo-2)PK(15)(Mv1Lu)ACE2,ACE2,293TMRC-5HCT-8,SARS-CoVHeike[23]RT-PCRACE2,Huh-7Hep-2VeroE6ACE2,HeLaHOSC8166BL41NIH3T3ACE2,ACE2SARS412ACE2SARS(adultrespiratorydistresssyndrome,ARDS),ACE2ARDSImai[24]ACE2ARDS,ARDS,ACE2,ARDSACE2ARDS,ACE2ARDSKuba[25]SARS-CoVACE2,SARS-CoVSACE2,,ARDSACE2SARS,ACE2SARS-CoVSARS;ACE2SARS-CoV5ACE2ARDS,ACE2ARDS,ACE2,AngÒ,[1]PeirisJS,LaiST,PoonLL,etal.Coronavirusasapossiblecauseof23120086163ActaLabAnimSciSin,June,2008,Vol.16,No.3severeacuterespiratorysyndrome[J].Lancet,2003,361(9366):1319-13251[2]KsiazekTG,ErdmanD,GoldsmithCS,etal.Anovelcoronavirusassociatedwithsevereacuterespiratorysyndrome[J].NEnglJMed,2003,348(20):1953-19661[3]DrostenC,GuntherS,PreiserW,etal.Identificationofanovelcoronavirusinpatientswithsevereacuterespiratorysyndrome[J].NEnglJMed,2003,348(20):1967-19761[4]RotaPA,ObersteMS,MonroeSS,etal.:Characterizationofanovelcoronavirusassociatedwithsevereacuterespiratorysyndrome[J].Science,2003,300(5624):1394-13991[5]MarraMA,JonesSJ,AstellCR,etal.ThegenomesequenceoftheSARS-associatedcoronavirus[J].Science,2003,300(5624):1399-14041[6]LiW,MooreMJ,VasilievaN,etal.Angiotensin2convertingenzyme2isafunctionalreceptorfortheSARScoronavirus[J].Nature,2003,426(6965):450-4541[7]DonoghueM.,HsiehF,BaronasE,etal.Anovelangiotensin-convertingenzyme-relatedcarboxypeptidase(ACE2)convertsangiotensinItoangiotensin1-9[J].CircRes,2000,87(5):E1-E91[8]TipnisSR,HooperNM,HydeR,etal.Ahumanhomologofangiotensin-convertingenzyme.Cloningandfunctionalexpressionasacaptoprilinsensitivecarboxypeptidase[J].JBiolChem,2000,275:(43)33238-332431[9]MooreMJ,DorfmanT,LiW,etal.Retrovirusespseudotypedwiththesevereacuterespiratorysyndromecoronavirusspikeproteinefficientlyinfectcellsexpressingangiotensin-convertingenzyme2[J].JVirol,2004,78(19):10628-106351[10]RenX,GlendeJ,A-lFalahM,etal.AnalysisofACE2inpolarizedepithelialcells:surfaceexpressionandfunctionasreceptorforsevereacuterespiratorysyndrome-associatedcoronavirus[J].JGenVirol,2006,87(Pt6):1691-16951[11]JiaHP,LookDC,ShiL,etal.ACE2receptorexpressionandsevereacuterespiratorysyndromecoronavirusinfectiondependondifferentiationofhumanairwayepithelia[J].JVirol,2005,79(23):14614-146211[12]HarmerD,GilbertM,BormanR,etal.QuantitativemRNAexpressionprofilingofACE2,anovelhomologueofangiotensinconvertingenzyme[J].FEBSLett,2002,532(1-2):