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What are the four types of cell death?
Describe programmed cell death.
- Requires gene activation of specific genes.
- Prevention of auto-immune disease.
- Uncontrolled cell death.
- Protein precipitation.
- Leads to inflammation in tissue.
- ATP loss.
- Swelling of cells and organelles (burst).
Describe lysosomal/typeII/autophagic cell death.
- Formation of autophagic vessicles.
- "intermediate" step in some cases.
Cleavage of ___ can ___ apoptotic pathways.
When both pro- and anti-apoptotic signals are present ___.
Stronger signalling "wins"
What are some characteristics of apoptotis/cell death?
- Cell shrinkage
- Membrane blebbing
- Chromatin fragmentation
- Leaky mitochondria (Cyt C)
- Nuclear condensation
- Flipping of phosphatidyl serine to outside.
- Formation of apoptotic bodies.
What are the two basic apoptotic pathways?
- Extrinsic - death receptor
- Intrinsic - mitochondrial
Describe extrinsic pathway.
- Ligand binds to death receptor (TNF-a, dimer).
- Cytoplasmic side binds to FADD
- Procaspase 8/10 is cut to caspase 8/10 (active form).
- Caspase 8/10 activates procaspase 3 -> apoptosis, and Bid (which can lead to intrinsic).
Which apoptotic pathway can lead to the other?
Extrinsic can lead to intrinsic, but not vice versa.
Describe intrinsic pathway.
- Caspase 8 cuts BID.
- Bid sends Bax to mitochondial membrane to dimerize with Bak.
- Mitochondia is damaged/dimerized(Bax/Bak) - releases Cyt C
- Cyt C cuts procaspase 9 to caspase 9 (active form).
- Caspase 9 and Apaf-1 bind to from Apoptosome (7-er)
- Apoptosome activates caspase3 -> apoptosis.
- Cut to Flips - survival.
- Cut to FlipL - high concentration apoptotic.
- low concentration survival.
Pathways are dependent on ___.
The BCL2 family including ___, can be ___ or ___.
- Bax, Bak, Bid, etc.
Integrin binding to ECM leads to ___ including what three proteins?
- Survival pathway.
- JNK, AKT, ERK
Pro-caspases are activated by ___.
Study of apoptosis has led to therapies that might be helpful in treating ___.