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What are the four types of cell death?
- Programmed
- Necrosis
- Apoptosis
- Lysosomal/TypeII/autophagic
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Describe programmed cell death.
- Embryonic.
- Requires gene activation of specific genes
- Prevention of auto-immune disease
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Describe necrosis.
- Uncontrolled cell death.
- Protein precipitation.
- Leads to inflammation in tissue.
- ATP loss.
- Swelling of cells and organelles (burst).
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Describe apoptosis.
Caspase-dependent.
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Describe lysosomal/typeII/autophagic cell death.
- Caspase-independent.
- Formation of autophagic vessicles.
- "intermediate" step in some cases.
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Cleavage of ___ can ___ apoptotic pathways.
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When both pro- and anti-apoptotic signals are present ___.
Stronger signalling "wins"
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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.
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What are the two basic apoptotic pathways?
- Extrinsic - death receptor
- Intrinsic - mitochondrial
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Describe extrinsic pathway.
- Ligand binds to death receptor (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).
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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.
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Describe Flip.
- Cut to Flips - survival.
- Cut to FlipL - high concentration apoptotic.
- low concentration survival.
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Pathways are dependent on ___.
Cell type
-
The BCL2 family including ___, can be ___ or ___.
- Bax, Bak, Bid, etc.
- Survival
- Apoptotic
-
Integrin binding to ECM leads to ___ including what three proteins?
- Survival pathway.
- JNK, AKT, ERK
-
Pro-caspases are activated by ___.
BCl-2 proteins
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Study of apoptosis has led to therapies that might be helpful in treating ___.
Cancer
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