北大细胞生物学课件13细胞凋亡.pptVIP

Chapter 13;PRIZED Horvitz, and Sulston share Physiology or Medicine Nobel （2002） “for their discoveries concerning genetic regulation of organ development and programmed cell death” ;机体结构;;?A simplified model of one way that mitogens stimulate cell division;Human cells have a built-in limitation on the number of times they can divide;; Morphological and biochemical characteristics of apoptosis;A、Normal cell ;? Biochemical characteristics of apoptosis :;Contrast ofApoptosis and necrosis;3.Molecular mechanisms of apoptosis;线虫体细胞凋亡研究：PCD相关基因15个，分为四组： 1、与PCD有关的基因，负责PCD控制：ced-3、ced-4和ced-9。 2、与PCD过程吞噬作用有关：ced-1、ced-2、ced-5-8 和 ced-10。 3、核酸酶基因（nuc-1）, 控制DNA降解，但非PCD所必须。 4、影响特异细胞类型PCD的基因：ces-1、ces-2、cgl-1、和 her-1. 保守性高，在哺乳动物中有相应同源物： Ced-3=ICE, Ced-4=Apaf-1, Ced-9=Bcl-2.; Apoptosis is carried out by a proteolytic system — caspase ;Apoptosis can be divided into two phases：; How to activate caspases?;Procaspases are activated by binding to adaptor proteins;The target proteins of caspase are the following: ;?The inhibitor of CAD (Caspase-activated Dnase, an endonuclease). Cleavage of CAD inhibitor lead to activation of CAD, once activated, CAD translocates from the cytosol to the nucleus severing DNA into fragments. ?Enzymes involved in DNA repair. Which are inactivated by caspase cleavage. DNA repair is a homeostatic activity that is inappropriate in an apoptotic cell. ; Molecular pathways of apoptosis;(1) Extrinsic pathway: Fas Signaling Pathway;;(2) Intrinsic pathway: Mitochondrial pathway;Activation of caspase-2 is required for permeabilization of mitochondria, release of cytochrome c, and apoptosis;Pathways to cell death in C. elegans and mammals