Cancer 6: apoptosis Flashcards
(22 cards)
What is the definition of necrosis?
-unregulated cell death associated with trauma, cellular disruption and an inflammatory response
What is the definition of apoptosis?
- regulated cell death, controlled disassembly of cellular contents without disruption
NO inflammatory response
What are the key features of necrosis?
- plasma membrane becomes permeable
- cell swelling and rupture of cellular membranes
- release of proteases leading to autodigestion and dissolution of the cell
- localised inflammation
What are the two phases of apoptosis?
latent phase
execution phase
What occurs during the execution phase
- loss of microvilli and intercellular junction
- cell shrinkage
- loss of plasma membrane asymmetry
- chromatin and nuclear condensation
- DNA fragmentation
- formation of membrane blebs
- fragmentation into membrane-enclosed apoptotic bodies
What is apoptosis- like PCD?
apoptosis like programmed cell death
- has some but not all the features of apoptosis
What is necrosis- like PCD?
variable features of apoptosis before cell lysis
Which are the initiator caspases?
2,8,9,10
-they have targeting subunits that direct them to a particular location
CARD - caspase recruitment domain
DED - death effector domain
How do caspases become active?
- procaspases undergo proteolytic cleavage to form large and small subunits
- after cleavage you will get folding of 2 large and 2 small chains to form active L2S2 heterotetramer
What are the main 3 aims of a caspase cascade
- amplification
- divergent responses
- regulation
WHat do the initiator caspases do?
trigger apoptosis by cleavage and activating
What do the effector caspases do?
-carry out the apoptotic programme
WHat 2 ways do the effector caspases carry out the apoptotic programme?
-cleave and inactivate protein or complexes e.g. nuclear lamins leading to nuclear breakdown
-
WHat 2 ways do the effector caspases carry out the apoptotic programme?
- cleave and inactivate protein or complexes e.g. nuclear lamins leading to nuclear breakdown
- activate enzymes e.g. CAD by direct cleavage or cleavage of inhibitory molecules
What are the mechanisms of caspase activation?
- death by design (receptor mediated pathways)
- death by default (mitochondrial death pathway)
What do death receptors in cells consist of?
- extracellular cystine rich domain
- singular transcellular domain
- cytoplasmic tail
the receptors are only activated when they come into contact with death ligands e.g. fas
Which two adaptor proteins are very important in the extrinsic pathway?
- FADD - positive regulator and promotes cell death
- FLIP - negative regulator, inhibits the death pathway
How does signalling occur through death receptors?
- Fas ligand binds to Fas receptor on the surface of cytotoxic T cells
- this causes trimerization of the death domains which the recruit the positive adapter protein FADD through its DD
- this causes the recruitment and oligomerisation of procaspase 8 through its DED to FADD DED
- This then causes a death inducing signalling complex (DISC)
What occurs next?
- procaspases bind via their DED domains to FADD
- this brings 3 initiator procaspases into close proximity, which allows cleavage and release of the active initiator caspase 8 tetramer
How many procaspases do you need to form an active tetramer?
at least 2
How does FLIP inhibit procaspase 8 activation?
- competes for binding to receptor tails via DED domains
- it incorporates into receptor-procaspase complexes and interferes with trans cleavage
Summarise what occurs during the mitochondrial regulation of apoptosis
internal stresses cause a loss of mitochondrial membrane potential
- this results in a release of cytochrome C and other apoptosis-inducing factors
- these stimulate the formation of the apoptosis complex
