Apolipoprotein JClusterin Is a Novel Structural Component of Human Erythrocytes and a Biomarker of Cellular Stress and Senescence 英文参考文献.docVIP
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Apolipoprotein JClusterin Is a Novel Structural Component of Human Erythrocytes and a Biomarker of Cellular Stress and Senescence 英文参考文献
ApolipoproteinJ/ClusterinIsaNovelStructural
ComponentofHumanErythrocytesandaBiomarkerof
CellularStressandSenescence
MariannaH.Antonelou1,AnastasiosG.Kriebardis1,2,KonstantinosE.Stamoulis3,IoannisP.
Trougakos1*,IssidoraS.Papassideri1*
1DepartmentofCellBiologyandBiophysics,FacultyofBiology,UniversityofAthens,Panepistimiopolis,Athens,Greece,2DepartmentofMedicalLaboratories,Facultyof
HealthandCaringProfessions,TechnologicalandEducationalInstituteofAthens,Athens,Greece,3BloodTransfusionCenter,Nikea,Piraeus,Greece
Abstract
Background:SecretoryApolipoproteinJ/Clusterin(sCLU)isaubiquitouslyexpressedchaperonethathasbeenfunctionally
implicatedinseveralpathologicalconditionsofincreasedoxidativeinjury,includingaging.Nevertheless,thebiologicalrole
ofsCLUinredbloodcells(RBCs)remainedlargelyunknown.InthecurrentstudyweidentifiedsCLUasacomponentof
humanRBCsandweundertookadetailedanalysisofitscellulartopology.Moreover,westudiedtheerythrocyticmembrane
sCLUcontentduringorganismalaging,inconditionsofincreasedorganismalstressandacceleratedRBCssenescence,as
wellasduringphysiologicalinvivocellularsenescence.
Methodology/Principal Findings: By using a combination of molecular, biochemical and high resolution microscopical
methods we found that sCLU is a novel structural component of RBCs extra- and intracellular plasma membrane and
cytosol.WeobservedthattheRBCsmembrane-associatedsCLUdecreasesduringorganismalagingorexposuretoacute
stress(e.g.smoking),inpatientswithcongenitalhemolyticanemia,aswellasduringRBCsinvivosenescence.Inallcases,
sCLUreductionparalleledtheexpressionoftypicalcellularsenescence,redoximbalanceanderythrophagocytosismarkers
whicharealsoindicativeofthesenescence-andoxidativestress-mediatedRBCsmembranevesiculation.
Conclusions/Significance:WeproposethatsCLUatthematureRBCsisnotasilentremnantoftheerythroidprecursors,but
anactivecomponentbeingfunctionallyimplicatedinthesignallingmechanismsofcellularsenescenceandoxidativestress-
responsesinbothhealthyanddiseasedorganism.Theredu
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