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1、MolecularPharmacologyFastForward.PublishedonSeptember1,2005asdoi:10.1124/mol.105.015412MOL(2005/015412)TitlepageSulfatedpolymannuroguluronate(SPMG),anovelanti-acquiredimmunedeficiencysyndrome(AIDS)drugcandidate,inhibitsTcellapoptosisviacombatingoxidativedamageofmitochon
2、driaaabaaa,*BenchunMiao,JingLi,XueyanFu,LiGan,XianliangXin,MeiyuGengaDepartmentofPharmacology,MarineDrugandFoodInstitute,OceanUniversityofChina,Qingdao266003,P.R.ChinabDepartmentofFoodScienceandTechnology,FoodScienceandEngineeringInstitute,OceanUniversityofChina,Qingdao
3、,266003,P.R.China.1Copyright2005bytheAmericanSocietyforPharmacologyandExperimentalTherapeutics.MOL(2005/015412)RunningtitlepageElucidationoftheprotectiveactionsofSPMGonTcellsCorrespondingauthor:MeiyuGengDepartmentofPharmacologyMarineDrugandFoodInstituteOceanUniversityof
4、ChinaQingdao266003P.R.ChinaTel.:0086-532-2032066Fax:0086-532-2033054E-mailaddress:gengmy@mail.ouc.edu.cn(MeiyuGeng)Numberoftextpages:39Numberoftables:1Numberoffigures:7Numberofreferences:40NumberofwordsintheAbstract:162NumberofwordsintheIntroduction:305Numberofwordsinth
5、eDiscussion:933Abbreviations:SPMG,sulfatedpolymannuroguluronate;AIDS,acquiredimmunedeficiencysyndrome;HIV,humanimmunodeficiencyvirus;MMP,mitochondrialmembranepotential;HPLC,highperformanceliquidchromatography;FITC,fluorescein-5-isothiocyanate;PMSF,phenylmethylsulphonylf
6、luoride;ESI-MS,electrosprayionization-massspectrum;ROS,reactiveoxygenspecies;SDS-PAGE,sodiumdodecylsulfatepolyacrylamidegelelectrophoresis.2MOL(2005/015412)AbstractSulfatedpolymannuroguluronate(SPMG)hasenteredthePhaseIIclinicaltrialasthefirstanti-acquiredimmunedeficienc
7、ysyndrome(AIDS)drugcandidateinChina.Herein,wereportthatSPMGwaseffectiveatprotectingTlymphocytesagainstapoptosis.FurtherstudiesindicatedthatSPMGsignificantlyelevatedmitochondrialmembranepotential(MMP)ofTcells,inhibitedmitochondrialreleaseofcytochromec(cytoc)inTcells,enha
8、ncedtheactivitiesofmitochondrialenzymecomplexI,IIIandV,andsubsequentlyincreasedATPlevelandATP/ADPratio.Inaddit
