Dysregulation of IRP1-Mediated Iron Metabolism Causes Gamma Ray-specific Radioresistance in Leukemia Cells 英文参考文献.docVIP
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Dysregulation of IRP1-Mediated Iron Metabolism Causes Gamma Ray-specific Radioresistance in Leukemia Cells 英文参考文献
DysregulationofIRP1-MediatedIronMetabolismCauses
GammaRay-specificRadioresistanceinLeukemiaCells
KurtisJ.Haro1,2,AneeshSheth1,2,DavidA.Scheinberg1,2
*
1MolecularPharmacologyandChemistryProgramandLeukemiaService,MemorialSloan-KetteringCancerCenter,NewYork,NewYork,UnitedStatesofAmerica,2Weill
CornellGraduateSchoolofMedicalSciences,DepartmentofPharmacology,NewYork,NewYork,UnitedStatesofAmerica
Abstract
Ironisrequiredfornearlyallorganisms,playingimportantrolesinoxygentransportandmanyenzymaticreactions.Excess
iron,however,canbecytotoxic.Emergingevidencesuggeststhatradioresistancecanbeachievedinlowerorganismsby
theprotectionofproteins,butnotDNA,immediatelyfollowingionizingradiation(IR)exposure,allowingforimprovedDNA
repair.Onepotentialmechanismforproteinprotectioniscontrollingandlimitingtheamountoffreeironincells,ashas
beendemonstratedintheextremophileDeinococcusRadiodurans,reducingthepotentialforoxidativedamagetoproteins
duringexposuretoIR.Wefoundthatironregulatoryprotein1(IRP1)expressionwasmarkedlyreducedinhumanmyeloid
leukemia HL60cells resistant tolow linearenergy transfer (LET) gammarays, but nottohigh LET alpha particles. Stable
knockdownofIRP1byshort-hairpinRNA(shRNA)interferenceinradiosensitiveparentalcellsledtoradioresistancetolow
LETIR,reducedintracellularFentonchemistry,reducedproteinoxidation,andmorerapidDNAdouble-strandbreak(DSB)
repair.Themechanismofradioresistanceappearedtoberelatedtoattenuatedfreeradical-mediatedcelldeath.Controlof
intracellularironbyIRPsmaybeanovelradioresistancemechanisminmammaliancells.
Citation: Haro KJ, Sheth A, Scheinberg DA (2012) Dysregulation of IRP1-Mediated Iron Metabolism Causes Gamma Ray-specific Radioresistance in Leukemia
Cells.PLoSONE7(11):e48841.doi:10.1371/journal.pone.0048841
Editor:DominiqueHeymann,Faculte′ deme′decine deNantes,France
ReceivedApril11,2012;AcceptedOctober1,2012;PublishedNovember14,2012
Copyright: ? 2012 Haro et al. This is an open-access article distributed under the terms of the Creative Commons Att
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