Cell Death Flashcards
What are the mechanisms of cell death?
Apoptosis Necrosis Necroptosis Autophagy Anoikis Senescence
What caspases are utilized in necroptosis?
None, it is a caspase-independent form of ‘cell suicide’ that is pro-inflammatory
What is the signaling pathway of necroptosis?
1) TNFa engages TNFR1
2) RIPKs are activated (ripoptosome)
3) MLKL is phosphorylated and permeabilizes membranes, releasing DAMPs
What is mitotic catastrophe?
If cells are unable to properly segregate their chromosomes (e.g. anaphase bridge), there is considerable DNA damage/lost. The loss of DNA triggers cell death in a delayed fashion
What are markers of cellular senescence?
p16 and SA-beta-gal
When do the following occur after radiation:
1) apoptosis
2) mitotic catastrophe
3) necrosis
1) 6-24h
2) 15h to 2w
3) days to weeks; can occur within hours at very high doses
What is the intrinsic apoptosis pathway?
1) ATM sense DNA damage and signals p53
2) p53 activates Bax/Bak/Bad
3) Bax/Bak/Bad place pores in mitochondrial membrane, releasing cytochrome c
3) Cyt c activates caspase 9
What is the extrinsic apoptosis pathway?
1) Fas or TNFR receptor is engaged
2) caspase 8 is activated
What are the initiator caspases?
8 (extrinsic) and 9 (intrinsic)
How does EBV interrupt apoptosis?
makes a viral homolog of bcl-2
How does HPV interrupt apoptosis?
E6 degrades p53
E7 binds Rb, releasing E2F
Describe the jejunal crypt stem cell assay
1) Mice intestines irradiated to destroy villi
2) After 3-4 days, crypts start to regenerate
3) count crypts per circumference
Describe the bone marrow stem cell assay
1) Experimental mice (donors) irradiated with an experimental dose
2) Recipient mice irradiated with an ablative dose (>9Gy)
3) Experimental mouse marrow injected into recipient mice
4) After 10 days, isolate spleen and count colonies
Describe the skin island assay
1) Ablative dose of radiation used to create a necrotic skin ‘moat’
2) island in the middle irradiated with a test dose
3) in 12-24 days, count the nodules that arise
