Functional Induction of the Cystine-Glutamate Exchanger System Xc- Activity in SH-SY5Y Cells by Unconjugated Bilirubin 英文参考文献.docVIP

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Functional Induction of the Cystine-Glutamate Exchanger System Xc- Activity in SH-SY5Y Cells by Unconjugated Bilirubin 英文参考文献.doc

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Functional Induction of the Cystine-Glutamate Exchanger System Xc- Activity in SH-SY5Y Cells by Unconjugated Bilirubin 英文参考文献

FunctionalInductionoftheCystine-Glutamate ExchangerSystemXc-ActivityinSH-SY5YCellsby UnconjugatedBilirubin PabloJ.Giraudi1.,CristinaBellarosa1*.,CarlosD.Coda-Zabetta1,PaoloPeruzzo1,ClaudioTiribelli2. 1CentroStudiFegato,FondazioneItalianaFegato,Trieste,Italy,2DipartimentoUniversitarioClinicodiScienzeMediche,ChirurgicheedellaSalute,Universita`DegliStudi diTrieste,Trieste,Italy Abstract WehavepreviouslyreportedthatexposureofSH-SY5Yneuroblastomacellstounconjugatedbilirubin(UCB)resultedina + markedup-regulationofthemRNAencodingfortheNa -independentcystine:glutamateexchangerSystemXc2(SLC7A11 andSLC3A2genes).InthisstudywedemonstratethatSH-SY5YcellstreatedwithUCBshowedahighercystineuptakedue to a significant and specific increase in the activity of System Xc2, without the contribution of the others two cystine transporters(XAG2andGGT)reportedinneurons.Thetotalintracellularglutathionecontentwas2foldshigherinthecells exposedtobilirubinascomparedtocontrols,suggestingthattheinternalizedcystineisusedforgluthathionesynthesis. Interestingly,thesecellsweresignificantlylesssensitivetoanoxidativeinsultinducedbyhydrogenperoxide.IfSystemXc2 issilencedtheprotectionislost.Inconclusion,theseresultssuggestthatbilirubincanmodulatethegluthathionelevelsin neuroblastomacellsthroughtheinductionoftheSystemXc2,andthisrendersthecelllesspronetooxidativedamage. Citation:GiraudiPJ,BellarosaC,Coda-ZabettaCD,PeruzzoP,TiribelliC(2011)FunctionalInductionoftheCystine-GlutamateExchangerSystemXc-Activityin SH-SY5YCellsbyUnconjugatedBilirubin.PLoSONE6(12):e29078.doi:10.1371/journal.pone.0029078 Editor:MasatoAsanuma,OkayamaUniversityGraduateSchoolofMedicine,DentistryandPharmaceuticalSciences,Japan ReceivedMarch22,2011;AcceptedNovember21,2011;PublishedDecember27,2011 Copyright: ? 2011 Giraudi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsource