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1、NitricOxide32(2013)36–42ContentslistsavailableatSciVerseScienceDirectNitricOxidejournalhomepage:www.elsevier.com/locate/ynioxUricacidattenuatesnitricoxideproductionbydecreasingtheinteractionbetweenendothelialnitricoxidesynthaseandcalmodulininhumanumbilicalveinendothelialcel
2、ls:Amechanismforuricacid-inducedcardiovasculardiseasedevelopmenta,1a,1abc,?a,?Jung-HyunPark,YoonMiJin,SoojinHwang,Du-HyongCho,Duk-HeeKang,InhoJoaDepartmentofMolecularMedicine,EwhaWomansUniversitySchoolofMedicine,Seoul158-710,SouthKoreabDepartmentofNeuroscience,SchoolofMedic
3、ine,KonkukUniversity,1Hwayangdong,Gwangjin-gu,Seoul143-701,SouthKoreacDivisionofNephrology,DepartmentofInternalMedicine,EwhaWomansUniversitySchoolofMedicine,Seoul158-710,SouthKoreaarticleinfoabstractArticlehistory:Theelevatedlevelofuricacidinthebodyisassociatedwithincreased
4、riskofcardiovasculardiseases,Received22January2013whichismediatedbyendothelialdysfunction.However,itsunderlyingmechanismisnotfullyunder-Revised2April2013stood,althoughdysregulationofendothelialnitricoxide(NO)productionislikelytobeinvolved.UsingAvailableonline23April2013huma
5、numbilicalvascularendothelialcells(HUVEC),weexploredthemolecularmechanismofuricacidonendothelialNOsynthase(eNOS)activityandNOproduction.Althoughhighdoseofuricacid(12mg/dlKeywords:for24htreatment)signi?cantlydecreasedeNOSactivityandNOproduction,itdidnotaltereNOSexpres-Uricac
6、id1177495114sionandphosphorylationsateNOS-Ser,eNOS-ThrandeNOS-Ser.Underthiscondition,wealsoNitricoxidefoundnoalterationsinthedimerizationandacetylationofeNOS,comparedwiththecontrol.Further-EndothelialnitricoxidesynthaseCalmodulinmore,uricaciddidnotchangetheactivityofarginas
7、eII,anenzymedegradingL-arginine,asubstrateCardiovasculardiseaseofeNOS,andintracellularlevelofcalcium,acofactorforeNOSactivation.Wealsofoundthaturicaciddidnotalterxanthineoxidaseactivity,suggestingnoinvolvementofxanthineoxidase-derivedOpro-2ductionintheobservedinhibitoryeff
8、ects.Invitroandincellcoimmunoprecipitationstudies,however,revealedthaturicacidsign
