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Brain Activation by Peptide Pro-Leu-Gly- (MIF-1)英文文献资料.doc

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Brain Activation by Peptide Pro-Leu-Gly- (MIF-1)英文文献资料

HindawiPublishingCorporation InternationalJournalofPeptides Volume2010,ArticleID537639,10pages doi:10.1155/2010/537639 ResearchArticle BrainActivationbyPeptidePro-Leu-Gly-NH2(MIF-1) ReasS.Khan, 1 ChuanhuiYu, 1 1 AbbaJ.Kastin, YiHe, RudolphH.Ehrensing, 1 1 2 andWeihongPan 1 HungHsuchou, KirstenPruferStone, 1 1 2 Blood-BrainBarrierGroup,PenningtonBiomedicalResearchCenter,BatonRouge,LA70808,USA TheOchsnerClinicFoundation,NewOrleans,LA70121,USA CorrespondenceshouldbeaddressedtoWeihongPan,weihong.pan@ Received26October2009;Revised12January2010;Accepted13January2010 AcademicEditor:YvetteTach′e Copyright?2010ReasS.Khanetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense, whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited. MIF-1 (Pro-Leu-Gly-NH2) is a tripeptide for which the therapeutic potential in Parkinson’s disease and depression has been indicatedbymanystudies.However,thecellularmechanismsofactionofMIF-1arenotyetclear.Here,weshowthespeci?cbrain regionsresponsivetoMIF-1treatmentbyc-Fosmapping,anddeterminethekineticsofcellularsignalingbywesternblotting ofpERK,pSTAT3,andc-Fosinculturedneurons.Theimmunoreactivityofc-Foswasincreased4hoursafterMIF-1treatment inbrainregionscriticallyinvolvedintheregulationofmood,anxiety,depression,andmemory.Thenumberofcellsactivated wasgreaterafterperipheraltreatment(intravenousdelivery)thanafterintracerebroventricularinjection.InculturedSH-SY5Y neuronalcells,c-Foswasinducedtime-anddose-dependently.Theactivationofcellularc-Foswasprecededbyatransientincrease ofmitogen-activatedproteinkinasepERKbutareductionofphosphorylatedSignalTransducerandActivatorofTranscription (pSTAT3)initially.WeconcludethatMIF-1canmodulatemultiplecellularsignalsincludingpERK,andpSTAT3toactivatec-Fos. Thecellularactivationinspeci?cbrainregionsillustratesthebiochemicalandneuroanatomicalbasisunderlyingthetherapeutic e?ectofMIF-1inParkinson’sdiseaseanddepre