CELL SENESCENCE AND DEATH - PowerPoint PPT Presentation

About This Presentation
Title:

CELL SENESCENCE AND DEATH

Description:

cell senescence and death ... – PowerPoint PPT presentation

Number of Views:606
Avg rating:3.0/5.0
Slides: 47
Provided by: cell75
Category:

less

Transcript and Presenter's Notes

Title: CELL SENESCENCE AND DEATH


1
???????????
CELL SENESCENCE AND DEATH
2
??? ????
  • Aging ,Senescence,?????????,??????????,???????????
  • ??????????,?????????????????????????????

3
???????????
  • ??????????????????????????3?? ???? ? ?????
    ??????
  • ??????????,???????
  • ??????????,??????
  • ????????????????

4
?????????(?)????
5
(?)???????
  • 1. DNA???????,??DNA?mtDNA???DNA???????????,??????
    ??
  • 2.  RNA?????
  • 3. ???????,????????
  • 4.  ????????????,????
  • 5. ????????????

6
???????????
  • 1. ??????????,?????(AD)?????ß-??????
  • 2.???DNA???????????,mtDNA?????,???????
  • ?????????????,???????
  • caloric restriction???????50-70?

7
  • Thin rat bury fat rat
  • The rats are both 1000 days old, very old for
    rats. The one on the right was calorie
    restricted. The one on the left is near death and
    shows typical signs of old age similar to what
    happens in humans.
  • Image cited from Clive McCay 1939.

8
3.?????(free radical theories)
  • ????????????????,???????????????(?OH)?????(H)??
    ??????????
  • ????????(???)?????
  • ????????????????????????????(?MFO)?????????

9
  • ??????DNA???????????????,????DNA?OH8dG????????
  • ??????????????????
  • ???SOD?CAT?GSH-PX?
  • ???????E???????
  • Orr?Sohal(1994),?SOD??????,?????????1/3?

10
4.?????(programmed senescence)
  • ???????????????????????,??????????????????
  • ?1. ?????,???????????????(cAAT)?A?,??????,??????B?
    cAAT
  • ?2. ??????????2???????

11
5.?????(replicative senescence)
  • ???????????,?Hayflick??????????????60-70??
  • DNA????????????,??????,???DNA????,????????????????
    ??14-18bp?
  • ????????,???????????

12
6. ??????
  • ?????????????????????????????
  • ??????39???,47???????????1???,1218?????
  • ?????????????? ?
  • ???,??????(SAG)????,?senescent cell derived
    inhibition of DNA synthesis ?

13
  • Werner's syndrome

A 37 years old patient, Adoue DFP 1997
14
  • Hutchinson-Gilford syndrome

15
??? ???????
  • ???????????????????????????,????????????????

16
?????????
  • (?)????
  • ??????????,??????????
  • ?????????????????
  • ?????????????????,?????(autolysis)???????????????
    ??,????(heterolysis)?

17
  • ??????,???????????????,??????????,???????,????????
    ?
  • ?????,????????,???/??????????
  • ??????,???????(??????)?
  • DNA????,???????,?????

18
(?)????
  • ??????????????????
  • ???????????????
  • ??????
  • ???????????,????????
  • ??????,DNA????,????????
  • ???????????,?????????

19
www.roche-applied-science.com/
20
????
??
??
21
????
??
??
22
(No Transcript)
23
(?)???????
  • ???????(PCD)?????????????????
  • PCD?????????????
  • PCD??????,?????????
  • PCD????????,????????????
  • PCD???????????

24
  • C. elegans???PCD?????(?????,?????)?
  • http//www.news.wisc.edu

25
  • C. elegans???1031??????1000??????
  • ?????302?????,???407?????,105??????PCD?
  • ????PCD????Ced-3?Ced-4?Ced-9?
  • Ced-3? Ced-4????
  • Ced-9??Ced-3?Ced-4????

26
2002?10?7????Sydney ????Horvitz????Sulston
,??PCD???????????????????
  • Sydney Brenner

H. Robert Horvitz
John E. Sulston
27
???????????????
  • (?)?????
  • 1. ????????????(????)??????????
  • 2. ??????????
  • 3. ?????????DNA?????????????????

28
  • Sculpting the digits in the developing mouse paw
    by apoptosis(Wood 2000)

29
(?)?????
  • 1. ?????
  • ????HIV
  • ????Poxvirus
  • 2. ??????
  • ??,??????
  • 3. ??????
  • ???????(AD,????)?????? ??????????????

30
???????????
  • 1. ???,??,??
  • 2. DNA????ladder
  • 3. ?????
  • 4. ?????????
  • 5. ?????
  • 6. Annexin V????????PS
  • 7. TUNEL???

31
  • 8. ???????????
  • ??????(FDA),????,??????
  • Hoechst 33342?33258,DAPI,???(AO),???,?????????????
    ?
  • ????(EB)?????(PI)?????D(7-AAD),???,??????????
  • ????????????????????

32
  • Human embryo at day 4 morula containing 23 nuclei
    labelled with DAPI (blue), including seven
    TUNEL-labelled condensed nuclei (pink, arrow)
    that were excluded from development (Kate Hardy
    1999).

33
??? ?????????
34
????????????
  • ????????????????????????????
  • ??????ICE?Apaf-1?Bcl-2?Fas/APO-1?c-myc?p53?ATM? ?

35
1.Caspase??
  • ??????ced-3,????????????
  • ???????cys??????
  • ????asp??????,??caspase(cysteine
    aspartate-specific protease)?
  • ??????????,??????????????,????????

36
  • Caspase classification(Zimmermann 2001)

Executioner or effector
Autocatalytic initiator
37
2.Apaf-1
  • ???????-1(apoptotic protease activating
    factor-1),???????ced-4?
  • ???????????,??????,????????,??????
  • Apaf-1?cyt c?ATP/dATP???,??caspase-9,?????(apoptos
    ome),??caspase-3,??caspase?????

38
3. bcl-2????
  • ??1-4?Bcl-2?????(BH1-4)?????????,?Bcl-2?????,?
    Bax?
  • ??????????????????,??cyt c??,?????
  • bcl-2??????ced9???????????????ER????,???????????

39
  • Bcl-2 gene family(Zimmermann 2001)

40
4. Fas
  • fas???APO-1,?TNF?????
  • 1993????????????????CD95?
  • fas??????????45KD??????
  • Fas???Fas????Fas??,???????caspase?

41
  • 5.P53
  • ?????????????DNA?????ATM??p53,??????,???Fas???,???
    ??
  • 6.Myc
  • ????,??????,Bcl-2?????,??????,?????????
  • 7. ATM
  • ?DNA???????????,???P53?

42
(?)Fas???????
  • Fas??????????,?????DD?(Death domain)?????FADD?DD??
    ??
  • FADD N???DED?(death effector domain)?Caspase-8????
    ,Caspase-8??????? ?

43
  • Caspase-8??caspase????,??Caspase-3?6?7?
  • Caspase???????????????????????????
  • Caspase????CAD( caspase-activated Dnase
    )?????,???CAD,CAD?????,??????????DNA?

44
  • ?????(type I),??????,caspase-8????????????,???Bcl-
    2????Fas?????
  • ?????(type II),?????, Caspase- 8????,?????????????
    ???
  • Caspase?????PT???,??????
  • Cyt c??????????Caspase-9,?????Caspase-3,???????

45
  • Mitochondria function during cell apoptosis

R. Chris Bleackley and Jeffrey A. Heibein 2001
46
  • Next topic is tumor cell.
Write a Comment
User Comments (0)
About PowerShow.com