通过葡萄糖诱导氧化应激，刺激血管内皮细胞中的NADPH氧化酶4活性和表达的增加

《通过葡萄糖诱导氧化应激，刺激血管内皮细胞中的NADPH氧化酶4活性和表达的增加》由会员上传分享，免费在线阅读，更多相关内容在教育资源-天天文库。

1、IncreasedactivityandexpressionofNADPHoxidase4stimulatedbyglucoseinducesoxidativestressinvascularendothelialcellsJianLIKeyLaboratoryofGeriatrics,BeijingInstituteofGeriatrics,MinistryofHealth,Beijing100730,Chinaβ-cellliverobesityβ-CellDysfunctionInsulinResistanceFFAVLDLFFAVLDLGlucoseOx

2、idativestressHypothesisRedox"rheostat“incellsWherearereactiveoxygenspeciesgenerated?Mitochondrialrespirtion-chainenzymecomplexxanthineoxidase,NOS,lipoxygenasePhagocyteNADPHoxidaseNADPHoxidaseofnon-phagocyticcells＊NADPHoxidaseisamajorsourceofvascularROSproduction.NOX-typeNADPHoxidases

3、assuperoxide-producingenzymesFeFeoutsideinsideIVIIVIIIIIVNH2HHHHHHNADPHFADCOOHH115O2O2-e-StructureoftheNADPHoxidaseTheNOXfamilyofNADPHoxidasesgp91phoxhomologyEF-handsNox1colonNox2phagocytesNox3innerearNox4kidneyandvascularcellsNox5testisandlymphoidtissuesO2O2-NADPHe-ABCDDPI:NOXinhib

4、itor;Rotenone:inhibitorofmitochondrialrespirtion-chainenzymecomplex;L-NAME:NOSinhibitor;Oxypurinol:xanthineoxidaseinhibitorNADPHoxidaseisamajorsourceofvascularROSproductioninducedbyglucoseA:negativecontrol;B:HUVEC;C:20mMglucosetreatedHUVEC;D:positivecontrolGlucoseinducesapoptosisofHU

5、VECAGCCGCGC:HUVEC;G:20mMglucose-treatedHUVECWesternblotGlucoseup-regulatestheexpressionofNOX4β-actinNOX4NOX2p22phoxp47phoxp67phoxRac1MAN1N2N3N4p22p47p67Rac1RT-PCR0102030glucose(mM)A:negativecontrol;B:transfectedwithGFP-pcDNA3.1;C:transfectedwithNOX4-pcDNA3.1Over-expressionofNOX4incre

6、asesthelevelofROSandresultsinapoptosisABCABCABCABCNOX4-siRNAdecreasestheexpressionofNOX4andthelevelROSinHUVECCC+GS-FAMS-FAM+GS-NOX4S-NOX4+GCS-FAMS-NOX4******MechanismforincreasedROSproductioninducedbydiabetesandinsulin-resistantstateDiabetesHighglucoselevelInsulinresistanceObesityEle

7、vatedNEFAlevelDenovoDAGsynthesisVascularcellsPKCactivationNADPHoxidaseactivationSuperoxideROSActivationofNADPHoxidaseImmunoflurescencestainingofp47phoxPKC/p47phoxregulatestheactivationofNOX4ROSlevelControlNaOHDMSOHypericinGlucosePMAROSlevelControlGlucoseDPIApocininSchematicillustrati

8、onofROS-medi