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Angiotensin II Increased Neuronal Stem Cell Proliferation Role of AT2R.doc

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Angiotensin II Increased Neuronal Stem Cell Proliferation Role of AT2R

AngiotensinIIIncreasedNeuronalStemCell Proliferation:RoleofAT2R JieChao1,LuYang2,ShilpaBuch2,LieGao1* 1DepartmentofCellularandIntegrativePhysiology,UniversityofNebraskaMedicalCenter,Omaha,Nebraska,UnitedStatesofAmerica,2DepartmentofPharmacology andExperimentalNeuroscience,UniversityofNebraskaMedicalCenter,Omaha,Nebraska,UnitedStatesofAmerica Abstract AngiotensinII(AngII),knownapotentvasoactivesubstanceintherenin-angiotensinsysteminthebrain,playsacriticalrole insystemicbloodpressurecontrol.However,increasingevidenceindicatedthatthephysiologicalroleofAngIIgobeyond itsvasoactiveeffect.Inthepresentstudy,wedemonstratedthatAngIItype-1receptor(AT1R)andtype-2receptor(AT2R) were expressed in primary rat hippocampal neuronal stem cells (NSCs). Treatment of rat hippocampal NSCs with Ang II increasedcellproliferation.PretreatmentofNSCswithspecificAT2R,butnotAT1R,antagonistsignificantlysuppressedAng II-induced cell proliferation. Furthermore, Ang II stimulated ERK and Akt phosphorylation in NSCs. Pretreatment of MEK inhibitor, but not PI3K inhibitor, inhibited Ang II-induced ERK phosphorylation as well as cell proliferation. In addition, stimulation of NSCs with Ang II decreased expression of KV 1.2/KV 3.1 channels and blocked K+ currents which lie downstreamofERKactivation.Takentogether,thesefindingsunderpintheroleofAT2Rasanoveltargetthatregulatescell proliferationmediatedbyAngIIwithimplicationsfortherapeuticinterventionforregulationofneurogenesis. Citation: Chao J, Yang L, Buch S, Gao L (2013) Angiotensin II Increased Neuronal Stem Cell Proliferation: Role of AT2R. PLoS ONE 8(5): e63488. doi:10.1371/ journal.pone.0063488 Editor:RenpingZhou,RutgersUniversity,UnitedStatesofAmerica ReceivedDecember11,2012;AcceptedApril3,2013;PublishedMay15,2013 Copyright: ? 2013 Chao etal. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsource