氧化应激与糖尿病PPT课件.ppt

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1、OxidativeStressandDiabetesJianLiBeijingInstituteofGeriatricsMinistryofHealthRedox"rheostat“invascularcellsReactiveoxygenspecies(=ROS)O2O2-H2O2acidicpH,SuperoxydeDismutase(SOD)NADPHoxidaseSuperoxideanionHydrogenperoxideProposedfunctionsofROSkillingofmi

2、croorganismsDNAdamagecancerogenesisageingcelldeathNOinactivationandperoxynitritegenerationregulationofcellgrowthanddifferentiationregulationofcellfunctionoxygensensingactivationofredox-sensitivetranscriptionfactorsactivationofredox-sensitivesecondmesse

3、ngersystemsWhereandwhyarereactiveoxygenspeciesgenerated?Mitochondriaby-productoftheoxidativemetabolismPhagocyteNADPHoxidasemicrobialkillingNADPHoxidaseofnon-phagocyticcellscellgrowth,cellsignalingNOX-typeNADPHoxidasesassuperoxide-producingenzymesFeFeou

4、tsideinsideIVIIVIIIIIVNH2HHHHHHNADPHFADCOOHH115O2O2-e-TheNOXfamilyofNADPHoxidasesReview:Lambethetal.Novelhomologsofgp91phox.TrendsinBiochemicalSciences25:459-461,2000.gp91phoxhomologyEF-handsNox1colonNox2phagocytesNox3innerearNox4kidneyNox5testisandlym

5、phoidtissuesO2O2-NADPHe-StructureoftheNAD(P)HoxidaseCharacteristicsofneutrophilandvascularNAD(P)HoxidaseNAD(P)HOxidaseActivationAdenovirus-inducedoverexpressionofPKC-β2causesthemembranoustranslocationofp47phoxandp67phoxAmodelillustratinghowincreasedROS

6、productioninaccumulatedfatcontributestometabolicsyndromeMechanismforincreasedROSproductioninducedbydiabetesandinsulin-resistantstateLinkingvariousriskfactorstoROSgenerationinthedevelopmentofIDDMInitiationandamplificationoftheimmune/inflammatoryresponse

7、byROS-inducedNFκBactivationinβ-celldeathSchematicillustrationofROS-mediatedNFκBactivationElevatedglucoseandFFAlevelscontributetothepathophysiologyofdiabetesviathegenerationofROSTheroleofserinekinaseactivationinoxidativestressinducedinsulinresistanceVas

8、culareffectsofreactiveoxygenspecies(ROS)ModulationofcellularfunctionbyROSincardiovasculardiseasesPotentialroleofNADPHoxidaseinthepathogenesisofdiabeticnephropathyEffectofhighglucoselevelandPMAonROSproductioninaorticsmoothmusclecells(A)a