SiderocalinLcn2NGAL24p3 Does Not Drive Apoptosis Through Gentisic Acid Mediated Iron Withdrawal in Hematopoietic Cell Lines 英文参考文献.docVIP

Siderocalin/Lcn2/NGAL/24p3DoesNotDriveApoptosis ThroughGentisicAcidMediatedIronWithdrawalin HematopoieticCellLines ColinCorrenti1.,VeraRichardson2.,AllysonK.Sia3.,AshokD.Bandaranayake4,MarioRuiz5 ,Yohan SuryoRahmanto2,Zaklinaˇ Kovacˇevic′2,MatthewC.Clifton6,8,MargaretA.Holmes1,BrettK.Kaiser1, JonathanBarasch7,KennethN.Raymond3,DesR.Richardson2*,RolandK.Strong1* 1DivisionofBasicSciences,FredHutchinsonCancerResearchCenter,Seattle,Washington,UnitedStatesofAmerica,2IronMetabolismandChelationProgram,Discipline ofPathologyandBoschInstitute,UniversityofSydney,NSW,Australia,3DepartmentofChemistry,UniversityofCalifornia,Berkeley,California,UnitedStatesofAmerica, 4Department of Immunology, University of Washington, Seattle, Washington, United States of America, 5Instituto de Biolog?′a y Gene′tica Molecular, Universidad de Valladolid, UVa-CSIC, Valladolid, Spain, 6Emerald Biostructures, Bainbridge Island, Washington, United States of America, 7College of Physicians and Surgeons of ColumbiaUniversity,NewYork,NewYork,UnitedStatesofAmerica,8SeattleStructuralGenomicsCenterforInfectiousDiseases(SSGCID),Washington,UnitedStatesof America Abstract Siderocalin(alsolipocalin2,NGALor24p3)bindsironascomplexeswithspecificsiderophores,whicharelowmolecular weight,ferricion-specificchelators.Ininnateimmunity,siderocalinslowsthegrowthofinfectingbacteriabysequestering bacterial ferric siderophores. Siderocalin also binds simple catechols, which can serve as siderophores in the damaged urinarytract.Siderocalinhasalsobeenproposedtoaltercellularirontrafficking,forinstance,drivingapoptosisthroughiron efflux via BOCT. An endogenous siderophore composed of gentisic acid (2,5-dihydroxybenzoic acid) substituents was proposed tomediate cellular efflux. However, binding studies reported herein contradict the proposal that gentisic acid forms high-affinity ternary complexes with siderocalin and iron, or that gentisic acid can serve as an endogenous siderophoreatneutralpH.Wealsodemonstratethatsider