细胞凋亡与衰老讲义 Cell apoptosis

Morphological and biochemical characteristics of apoptosis
Morphologi changes:
Early : Chromosome condensation, cell body shrink Later : Blebbing and Nucleus and cytoplasm fragment— Apoptotic bodies At last: Phagocytosed
衰老
机体结构
细胞增殖
细胞分化
细胞凋亡
细胞信号转导
染色体
（DNA与蛋白质的相互作用）
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
Lane 1．0 h 2．1 h 2.0kbp 3．2 h 4．3 h 1.0 5．4 h 6．Control 0.5 7．Marker
0.2
Contrast ofApoptosis and necrosis
Apoptosis
Necrosis
Death by apoptosis is a neat, orderly process
A、Normal cell
B、Apoptosis: Apoptotic bodies
Biochemical characteristics of apoptosis :
180~200bp DNA ladder, Accumulation of tTG, PS flip-flop
Apoptosis induced by Cyto C
Cell apoptosis
1. Extracellular cotrol of cell division,
cell growth, and apoptosis
Mitogens stimulate G1-Cdk and G1/S-Cdk activities
1090 –131= 959(cells)
3.Molecular mechanisms of apoptos源自文库s
Early researches (MIT: Robert Horrid , 1986)
C. elegans:1090 cells, 131 cells death.
The Finding of CED3 mutant Without losing any of their
2.Apoptosis, Programmed cell death
Biological functions of apoptosis 细胞凋亡是多细胞生物在发育过程中，一种由基因控制
的主动的细胞生理性自杀行为。
In development, homeostasis, tumor
surveillance, and the function of the immune system.
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.
Mammalian: CED3 is related to mammalian interleukin1ß–converting enzyme (ICE or
Apoptosis is carried out by a proteolytic system — caspase
PRIZED Horvitz, and Sulston share Physiology or Medicine Nobel （2002） “for their discoveries concerning genetic regulation of organ development and programmed cell death”
(1) Why called caspase? Active site: Cysteine Cleavage site: Asparatic acid Cysteine Asparatic acid specific protease
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
The cell division is cotrolled not only by extracellular mitogens but also by intracellular mechanisms that can limit cell proliferation.
Cell-cycle arrest or apoptosis induced by excessive stimulation of mitogenic pathways.
cells to apoptosis.
CED3 gene play a crucial role in the process of apoptosis.
C elegans: a millimeter long, transparent body only a few cell types, from zygote to mature adult only in 3.5days.
Extracellular growth factors stimulate cell growth
Activation of cell-surface receptors
Activation of PI 3-kinase Activation of elF4E (translation initiation factor) and S6 kinase(phosphorylates ribosomal protein S6) Increasing protein synthesis and cell growth