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ID:208484
大小:1.83 MB
页数:33页
时间:2017-07-03
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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
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