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.
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
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.
