Uric acid attenuates nitric oxide production by decreasing the interaction between endothelial nitric oxide synthase and calmodulin in human umbilical vein endothelial cells

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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)significantlydecreasedeNOSactivityandNOproduction,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