文档介绍：生物细胞细胞凋亡与衰老
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PRIZED Horvitz, and Sulston share Physiology or Medicine Nobel
（2002）
“fo22年，星期一
Contrast ofApoptosis and necrosis
Apoptosis
Necrosis
Death by apoptosis is a neat, orderly process
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mechanisms of apoptosis
Early researches (MIT: Robert Horrid , 1986)
C. elegans:1090 cells,
The Finding of CED3 mutant
Without losing any of their
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 .
131 cells death.
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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.
Mammalian: CED3 is related to mammalian interleukin-
1ß–converting enzyme (ICE or caspase-1)
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Apoptosis is carried out by
a proteolytic system — caspase
(1) Why called caspase?
Active site: Cysteine
Cleavage site: Asparatic acid
Cysteine Asparatic acid specific protease
Aps-Xxx
天冬氨酸特异性的半光氨酸蛋白水解酶
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Apoptosis can be divided into two phases：
Activation phase：
The cell responds to “death signals” that commit it to undergoing self-destruction.
Execution phase：
The death sentence is carried out.
Apoptosis cells are recognized by phagocytes because they carry exposed markers, called “eat me” signals.
The best studied “eat me” signal is the presence of phosphatidylserine molecules in the outer leaflet of PM of apoptotic cells (by flop-flipase).
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How to activate caspases?
All caspases expressed as proenzymes— Procaspases
Procaspase
NH2-terminal prodomain: Highly variable
Large subunit (20kD)
Small subunit (10kD)
How are procaspases activ