《程序性细胞死亡与细胞衰老ppt》由会员分享，可在线阅读，更多相关《程序性细胞死亡与细胞衰老ppt（63页珍藏版）》请在金锄头文库上搜索。
1、第十三章 程序性细胞死亡与细胞衰老 Section 1: Programmed Cell Death (PCD) Cells are balanced between life and death DAMAGEPhysiological death signals DEATH SIGNALDEATH SIGNALDEATH SIGNALDEATH SIGNAL PROAPOPTOTIC PROTEINS ANTIAPOPTOTIC PROTEINS Three ways of animal cell death Apoptosis：细胞凋亡 Necrosis：细胞坏死 Autophagy：细胞
2、自噬 PCD Versus Apoptosis Apoptosis History: 1965, Kerr, Observance; Definition in 1972 Conception: Apoptosis(Apo-ptosis), interchangeably with “programmed cell death”: The cells activate an intracellular death and kill themselves in a controlled way History of cell death / apoptosis researchHistory o
3、f cell death / apoptosis researchHistory of cell death / apoptosis researchHistory of cell death / apoptosis researchHistory of cell death / apoptosis researchHistory of cell death / apoptosis researchHistory of cell death / apoptosis researchHistory of cell death / apoptosis research 1800sNumerous
4、observation of cell death 1908Mechnikov wins Nobel prize (phagocytosis) 1930-40Studies of metamorphosis 1948-49Cell death in chick limb 138:33-41. view abstract (2) Yuan J, Finney M, Kim S, Horvitz HR. Tc4, a C. elegans transposon with an unusual foldback structure. Proc. Natl. Acad. Sci. USA 199119
5、9119911991; 88:3334-3338. view abstract (3) Yuan J, Horvitz HR. The C. elegans cell death gene ced-4 encodes a novel protein and is expressed during the period of extensive programmed cell death. Development 1992199219921992; 116:309-320. view abstract (4) Yuan J, Shaham S, Ledoux S, Ellis HM, Horvi
6、tz HR. The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 converting enzyme. Cell 1993199319931993; 75: 641-652. view abstract download PDF (5) Miura M, Zhu H, Hartwieg EA, Rotello R, Yuan J. Induction of apoptosis in fibroblasts by interleukin-1 converting enz
7、yme, a mammalian homolog of C. elegans cell death gene ced-3. Cell 1993199319931993; 75: 653-660. view abstract download PDF (6) Gagliardini V, Fernandez PA, Lee RKK, Drexler HCA, Rotello R, Fishman M, Yuan J. Prevention of vertebrate neuronal death by the crmA gene. Science 1994199419941994; 263: 8
8、26-828. view abstract download PDF (7) Rotello R, Fernandez PA, Yuan J. Anti-apogens and anti-engulfens: monoclonal antibodies reveal specific antigens on cells undergoing programmed cell death in developing chick embryos. Development 1994199419941994; 120: 1421-1431. view abstract (8) Fernandez PA,
9、 Rotello R, Rangini Z, Doupe A, Yuan J. Expression of a specific marker of avian programmed cell death in both apoptosis and necrosis. Proc. Natl. Acad. Sci. 1994199419941994; 91:8641-8645. view abstract download PDF (9) Wang L, Miura M, Bergeron L, Zhu H, Yuan J. Ich-1, an Ice/Ced-3 related gene, e
10、ncodes both positive and negative regulators of programmed cell death. Cell 1994199419941994; 78:739-750. view abstract download PDF (10) Miura M, Friedlander RM, Yuan J. Tumor Necrosis Factor-induced apoptosis is mediated by a CrmA-sensitive cell death pathway. Proc. Natl. Acad. Sci. USA PNAS. 1995
11、199519951995; 92: 8318-8322. view abstract download PDF Apoptosis is carried out by Apoptosis is carried out by Apoptosis is carried out by Apoptosis is carried out by a proteolytic a proteolytic a proteolytic a proteolytic system system system system caspasecaspasecaspasecaspase (1) Why called casp
12、ase?(1) Why called caspase?(1) Why called caspase?(1) Why called caspase? Active siteActive siteActive siteActive site: Cysteine: Cysteine: Cysteine: Cysteine Cleavage siteCleavage siteCleavage siteCleavage site: Asparatic acid: Asparatic acid: Asparatic acid: Asparatic acid C C C Cysteine ysteine y
13、steine ysteine AspAspAspAsparatic aratic aratic aratic acid specific proteacid specific proteacid specific proteacid specific proteaseaseasease Aps-Xxx 天冬氨酸特异性的半光氨酸蛋白水解酶 How to activate caspases? How to activate caspases? How to activate caspases? How to activate caspases? All caspases expressed as
14、proenzymesAll caspases expressed as proenzymesAll caspases expressed as proenzymesAll caspases expressed as proenzymes Procaspases Procaspases Procaspases Procaspases ProcaspaseProcaspaseProcaspaseProcaspase NH2-terminal prodomainNH2-terminal prodomainNH2-terminal prodomainNH2-terminal prodomain: Hi
15、ghly variable: Highly variable: Highly variable: Highly variable Large subunit (20kD)Large subunit (20kD)Large subunit (20kD)Large subunit (20kD) Small subunit (10kD)Small subunit (10kD)Small subunit (10kD)Small subunit (10kD) How are procaspases activated to initiate the caspase cascade?How are pro
16、caspases activated to initiate the caspase cascade?How are procaspases activated to initiate the caspase cascade?How are procaspases activated to initiate the caspase cascade? The activation is triggered by adaptor proteins that bring multiple copies of The activation is triggered by adaptor proteins that bring multiple copies of The activation is triggered by adaptor proteins that bring multiple copies of The activation i
