Your SlideShare is downloading. ×
Upcoming SlideShare
Loading in...5

Thanks for flagging this SlideShare!

Oops! An error has occurred.


Saving this for later?

Get the SlideShare app to save on your phone or tablet. Read anywhere, anytime - even offline.

Text the download link to your phone

Standard text messaging rates apply



Published on



Published in: Technology

1 Comment
1 Like
No Downloads
Total Views
On Slideshare
From Embeds
Number of Embeds
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

No notes for slide
  • Transcript

    • 1. Apoptosis By : najmaldin saki 2008 Department of Hematology School of Medical Sciences Tarbiat Modares University
    • 2.  
    • 3.  
    • 4.  
    • 5.  
    • 6.  
    • 7. Caspases
    • 8. Ligand-induced cell death “ The death receptors” Ligand-induced trimerization FasL Trail TNF Death Domains Death Effectors Induced proximity of Caspase 8 Activation of Caspase 8
    • 9. CASPASES CAN BE INHIBITED BY VIRUSES ... CrmA ... Baculovirüs p35 ... Ebstein Barr Virüs BHRFI proteini ... Ebstein Barr V irüs LMP-1 proteini
    • 10. 3 mechanisms of caspase activation a. Proteolytic cleavage e.g. pro-caspase 3 b. Induced proximity, e.g. pro-caspase 8 c. Oligomerization, e.g. cyt c, Apaf-1 & caspase 9 Back
    • 11. Bcl-X L Bad Bcl-X L Bax Bcl-2 Bax Bax Bax Bcl-2 Bad CELL SURVIVAL CELL DEATH
    • 12.  
    • 13. Controlling the cell-proliferation and death machinery P53 is able to activate p21 P21 binds to the CDK-cyclin complex and inhibits its protein kinase enzymatic activity
      • - CDK’s target proteins are not phosphorylated
      • - Cell cycle is unable to progress
      • When the DNA mismatches have been repaired,
      • the drop of p53 levels & a cessation of inhibition
      G1-to-S checkpoint block The cell cycle: negative intracellular controls Intracellular signals
      • Fail-safe systems (checkpoints) ensure that the cell cycle does not progress
      • until the cell is competent.
    • 14. The bcl-2 family Receptor domain phosphorylation Raf-1 calcineurin Pore formation Membrane anchor Ligand domain BH4 BH3 BH1 BH2 TM N C Group I Group II Group III Bcl-2 bax Bad bid bik
    • 15. Bcl-2 Protein (with BH3 Peptide) Bcl-2 Protein
    • 16.  
    • 17.  
    • 18.
      • 65000 papers
      • Apoptsis in anucleate platelets wa first reported in 1997 by Vanags et al.
      • It was demonstrated that apoptosis within megakaryocytes & megakaryoblastic is causal for platelet production (NO , TNF α , BCL 2 )
    • 19.
      • Models of platelet apoptosis
      • apoptosis of platelets was induced by the calcium ionophores ionomycin , A23187 which induce apoptosis in nucleate cells.
      • apoptosis was provoked by platelet storage in culture where washed platelets were aged by incubation for 18–24 h at 37 C in a culture medium or plasma in capped tubes
      • apoptosis was induced by platelet aging in vitro during storage of leukodepleted platelet concentrates (PCs) under standard blood banking conditions at 22 C
      • apoptosis was associated with platelet aging in vivo in dogs with thrombopoiesis suppressed by estradiol injection .
      • platelet apoptosis was reported in mice with thrombocytopenia caused by malaria infection and induced by injection of TNF or anti-platelet antibodies
    • 20.
      • Apoptotic changes in platelet morphology
      • These morphologic changes included:
      • platelet shrinkage
      • cytoplasm condensation
      • plasma membrane blebbing
      • extension of filopodia.
      Originaly , these changes were described as “ platelet activation ” and only since 1997 did some investigetors begin to consider these morphologic chenges as apoptotic.
    • 21.  
    • 22. Li et al, found that platelets express mRNA for death ligand TRAIL , death receptors TNFR1, DR3 , DR4 and DR5 , and adapter proteins TRADD and RIP . In contrast , Fas receptor and Fas ligand were not detected in platelets as determined by mRNA and immunoblot and anti-Fas antibodies had no effect on platelets.
    • 23. ᴪ m In normal undamaged nucleate cells, mitochondria have a high ᴪ m; breakdown of ᴪ m is characteristic of early apoptosis . ᴪ m in platelets can be measured by the cell-permeable lipophilic cationic dyes JC-1 and DiOC6 . Using JC-1 , we have demonstrated depolarization of ᴪ m in PCs starting from days 13_14 of storage.
    • 24. Cytochrome c, Diablo/Smac and Apaf-1. Cytochrome C and Apaf-1 have been found by immunoblot in whole lysates of fresh nonactivated platelets.
    • 25.  
    • 26.