susceptibility of cem cell clones to gc-evoked apoptosiscem细胞克隆诱发细胞凋亡的gc敏感性

《susceptibility of cem cell clones to gc-evoked apoptosiscem细胞克隆诱发细胞凋亡的gc敏感性》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、ROLEOFINTRACELLULARCALCIUMINGLUCOCORTICOID-EVOKEDLYMPHOIDCELLAPOPTOSISDevinMorrisCaliforniaStateUniversity,NorthridgeApoptosisReleaseofcyctochromecEffectorCaspasesApoptosisStimuli/DeathsignalsApoptosomeformationActivationofcaspasecascadeApaf-1Caspase9ProliferationCellPopulationCellDeathDevelopment

2、HomeostasisDiseasePhysiologicalrolesofapoptosisRIPCABCIPCRIPCRRRRRligandreceptorinteractingproteinscoactivatorcomplexbasaltrans.factors1234GlucocorticoidPathwaySusceptibilityofCEMCellClonestoGC-EvokedApoptosisGC-inducedIncreaseinIntracellularCalciuminGC-SusceptibleCEMcellsTime-&GC-Dose-DependentInc

3、reasein[Ca+2]iinCEM-C7-14CellsEtOH100nMDex1mMDex24hours48hours4.4%6%14.1%5%24.8%62.1%ABCDEFModulatorsof[Ca+2]iLevelsInfluenceGC-EvokedDeathofCEMCellsEGTASuppressesGC-EvokedIncreasein[Ca+2]iLevelsinCEM-C7-14CellsEtOH100nMDex1mMDexEthanol20mMEGTAABCDEF4.4%16.4%35%2%12.4%23.1%GlucocorticoidSignalingP

4、athwayPathwayInhibitorsNormalPathwayInhibitionofCalmodulinProtectsCEM-C7-14CellsfromGC-evokedDeathInhibitionofCalmodulinKinaseIIProtectsCEM-C7-14CellsfromGC-evokedDeathInhibitionofCalcineurinProtectsCEM-C7-14CellsfromGC-evokedDeathConclusionsGCsincrease[Ca+2]ilevelsonlyintheGC-susceptibleCEM-C7-14c

5、elllineinadosedependentmanner;notintheGC-resistantsistercellline,CEM-C1-15.CalciumchelationbyeitherBAPTAorEGTAprotectedCEM-C7-14cellsfromGC-evokedapoptosis,inconjunctionwithareductionintheamountoffree[Ca+2]i.ThecalciumionophoreA23187causessensitizationofCEM-C1-15cellstoGC-evokedapoptosis.Inhibition

6、ofcalmodulin,calmodulinkinaseIIorcalcineurin,allintermediatesinthecalciumsignalingpathway,impartvaryingdegreesofprotectiontoCEM-C7-14cellsfromGC-evokedapoptosis.OurdatademonstrateaclearcorrelationbetweencalciumsignalingandGC-evokedapoptosisFutureGoalsFurtherstudieswillaimtounderstandCa+2-dependentc

7、hangesingeneregulationthatcontributetoapoptosis.CandidategenessuchasthetranscriptionalrepressorE4BP4,anditsdownstreamtargetsarebeingstudied.OurultimategoalistounderstandthemolecularpathwayforapoptosisinT-ly