史娟医科院基础(jīchǔ)所新科研楼607E-mail:shijuantt@yahoo.com细胞(xìbāo)凋亡和细胞(xìbāo)自噬第一页,共一百四十一页。第二页,共一百四十一页。Outline1.Historyofapoptosisresearch2.Characterizationofapoptosis3.PhysiologicalSignificances4.ApoptosisSignalingPathways5.RegulationofApoptosis6.ApoptosisandAutophagy第三页,共一百四十一页。第一节凋亡(diāowánɡ)的研究历史1842CarlVogetInitialobservationthatcelldeathinpartofnormaldevelopment1972Kerr,WyllieandCurrie--introducedterm‘apoptosis’todescribecelldeathwithasetofcommonmorphologicalfeatures-Celldeletionwascontrolledunderphysiologicalconditionsinadults-Deregulationcouldleadtomanydiseases-MorphologicallyidenticaltodevelopmentalCDanddistinctfromaccidentalcelldeath第四页,共一百四十一页。1980WyllieBiochemicalchangesinapoptoticmorphology:-DNAfragmentation-Requiresexpressionofdeathgenes1988Bcl-2wasfoundtobeanti-apoptotic1991cedgeneswereidentifiedinC.elegan1992Fas/APO-1/CD95wasidentified1993Aroleofp53inregulationofapoptosiswasdescribedFasligandwasidentifiedICEwasfoundtobehomologofced-3inmammalianIAPswereidentified1994Theroleofmitochondriaduringapoptosis1996TheroleofcaspasesduringapoptosisReleaseofcytochromecfrommitochondriaduringapoptosiswasdiscovered1997Apafswereidentified第五页,共一百四十一页。NobelPrize2002inPhysiologyandMedicineSydneyBrennerJohnE.SulstonRobertH.Horvitzfortheirdiscoveriesconcerning"geneticregulationoforgandevelopmentandprogrammedcelldeath"第六页,共一百四十一页。“GeneticcontrolofprogrammedcelldeathinthenematodeCaenorhabditiselegans”“Youcanobservealotbywatching.”Y.Berra第七页,共一百四十一页。第二节凋亡细胞(xìbāo)的特征第八页,共一百四十一页。凋亡(apoptosis)的形态学特征为染色质凝集、边缘化,细胞皱缩,细胞膜内侧的磷脂酰丝氨酸外翻,细胞出泡形成凋亡小体。细胞凋亡受到一系列相关(xiāngguān)基因的严格调控。程序性细胞死亡(programmedcelldeath,PCD),即是指细胞在一定的生理或病理条件下,遵循自身的程序,主动结束其生命的过程,这种死亡由基因决定的。大多数程序性细胞死亡,呈现细胞凋亡的形态学特征。第九页...