cell death Flashcards
how is the autophagosome formed?
portions of the cytoplasm are engulfed by a double membrane vacuole
how is the autolysosome formed?
autophagosome is acidified
how is autophagy “pro-survival”
helps cells to survive in times of low nutrients through catabolism
how is autophagy “pro-death”
through autophagy or the induction of apoptosis
which types of dlls can be observed undergoing autophagic death?
cells with accumulations of misfiled proteins- Huntington’s dz, prion dz, breast CA cells treated with tamoxifen
what will lead to the intrinsic pathway of apoptosis?
intracellular stressors (pH, oxidative stress, mitochondrial stress, DNA damage)
which are the anti-apoptotic proteins?
Bcl-2 and Bcl-xl
how do the anti-apoptotic proteins work?
present in the mito membrane, inhibit the function of pro-apoptotic proteins
which are the pro-apoptotic proteins?
Bax, Bak
how do the pro-apoptotic proteins function?
dimerization results (indirectly) in cytochrome c release (ions released first)
what are the “activators”? “decoys”?
activators- Bid and Bim
decoys- Bad, Bik
how do the “activators” work?
pro-apoptotic
help form the pore
how do the “decoys” work?
pro-apoptotic
inhibit the function of the anti-apoptotic
what is the initiator in the intrinsic pathway of apoptosis?
procaspase-9
discuss the steps in the intrinsic pathway of apoptosis
-cytochrome c is released from mito
-cytochrome c binds Apaf-1 adapter protein
-cytoC+Apaf-1 complexes will aggregate and bind procaspase-9 to form “apoptosome”
-procaspe-9 activated to caspase-9
-caspase cascade triggered
= apoptosis
what are the receptors used with extrinsic apoptosis?
Fas receptor, tumor necrosis factor receptor
what are FADD/TRADD?
death domains that include adapter proteins
what is the initiator for the extrinsic apoptosis pathway?
procaspase-8
what are some of the effects of the caspase cascade (intrinsic/extrinsic)?
DFF- DNA fragmentation factor
CD- caspase activated DNase
cleave lamins, fragment nucleus
externalized phos-serine –> “eat me signal”
what type of signaling is used in the extrinsic apoptosis pathway?
juxtracrine
describe the extrinsic apoptotic pathway
-fas-ligand on t-cell binds fas-protein on target
- adapter proteins facilitate binding of procaspases to receptor/ligand complexes
- procaspase-8 cleaved to caspase 8
- caspase cascade triggered
= apoptosis
what are the links between the intrinsic and extrinsic pathways of apoptosis? (2)
1- both caspase 8 and caspase 9 will activate caspase 3
2- caspase 8 (extrinsic) can cleave and activate Bid (pro-apoptotic activator) and trigger intrinsic pathway
when does anoikis occur?
when cell becomes detached from the ECM
what is the relation of anoikis to tumor mets?
anoikis must be overcome for mets to occur
