Altered Membrane Structure and Surface Potential in Homozygous Hemoglobin C Erythrocytes 英文参考文献.docVIP

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Altered Membrane Structure and Surface Potential in Homozygous Hemoglobin C Erythrocytes 英文参考文献.doc

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Altered Membrane Structure and Surface Potential in Homozygous Hemoglobin C Erythrocytes 英文参考文献

AlteredMembraneStructureandSurfacePotentialin HomozygousHemoglobinCErythrocytes FuyukiTokumasu1*,GlennA.Nardone2,GracielaR.Ostera1,RickM.Fairhurst3,StevenD.Beaudry3 ,Eri Hayakawa4,JamesA.Dvorak1 1BiophysicalandBiochemicalParasitologySection,LaboratoryofMalariaandVectorResearch,NationalInstituteofAllergyandInfectiousDiseases,NationalInstitutesof Health,Bethesda,Maryland,UnitedStatesofAmerica,2ResearchTechnologyBranch,NationalInstituteofAllergyandInfectiousDiseases,NationalInstitutesofHealth, Bethesda,Maryland,UnitedStatesofAmerica,3MalariaPathogenesisandHumanImmunityUnit,LaboratoryofMalariaandVectorResearch,NationalInstituteofAllergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America, 4International Research and Educational Institute for Integrated MedicalSciences(IREIIMS),TokyoWomen’sMedicalUniversity,Tokyo,Japan Abstract Background:HemoglobinCdiffersfromnormalhemoglobinAbyaglutamate-to-lysinesubstitutionatposition6ofbeta globinandisoxidativelyunstable.ComparedtohomozygousAAerythrocytes,homozygousCCerythrocytescontainhigher levelsofmembrane-associatedhemichromesandmoreextensivelyclusteredband3proteins.Thesefindingssuggestthat CCerythrocyteshaveadifferentmembranematrixthanAAerythrocytes. MethodologyandFindings:WefoundthatAAandCCerythrocytesdifferintheirmembranelipidcomposition,andthata subsetofCCerythrocytesexpressesincreasedlevelsofexternalizedphosphatidylserine.Detergentmembraneanalysesfor raftmarkerproteinsindicatedthatCCerythrocytemembranesaremoreresistanttodetergentsolubilization.Thesedata suggestthatmembraneraftorganizationismodifiedinCCerythrocytes.Inaddition,theaveragezetapotential(ameasure of surface electrochemical potential) of CC erythrocytes was 2mV lower than that of AA erythrocytes, indicating that substantialrearrangementsoccurinthemembranematrixofCCerythrocytes.Wewereabletorecapitulatethislowzeta potential phenotype in AA erythrocytes by treating them with NaNO2 to oxidize hemoglobin A molecules and