Topic 8: Apotosis Flashcards
what are the types of cell deaths?
- apoptosis
- necrosis
what is apoptosis
a rapid but controlled cell suicide program in animal cells lead by caspases where the insides are degraded
what is necrosis
it is when the cell dies due to tissue damage so all the insides come out
what is the function of the 3 types of proteins needed to cause apoptosis
1) Killer protein to initate the protein
2) Destruction proteins to digest DNA and protein in the dying cell
3) Engulfment Proteins that put a signal of the extracelluar surface of the cell to get it to be phagocyted
how does it look when a cell undergoes apoptosis?
it blebs and swells
how does it look when a cell undergoes necrosis?
it swells and circles until it explodes
how would an apoptosis cell look like in a gel?
it would have most of the down in chunks and slowly move down in chunks of 2-3 histomes
how would a necrosis cell look like in a gel?
it would be spread out because it isn’t in organized chunks
how can apoptotic cells be identified?
by TUNEL: TdT-mediated dUTP nick end labeling technique
- it labels the nicks found in DNA
what are caspases and what from do they start out in?
they are proteases with cystine in their active site and they cleave protiens that have asparagric acid residue
they start out in procaspase form
how does procapases turn into active initiator caspases?
caspases 8 & 9 are in pro cascade form until they get activated by adaptor proteins from an apopotic signal
what does an active intitator caspases (9) do?
it activates the executioner casapse by cleavage
what does the executioner caspases do?
capaseses 3, 6 and 7 cleave a wide variety of cellular proteins of the nuclei lamina and cytoskeleton that dismantles the cell
examples of proteins the executioner caspases cleave and why?
- flippases: causes cell asymmetry
- nuclear lamin: breaks nuclear envelope
- ICAD (inhibitor of capase-activated DNAase): makes CAD active and cleaves DNA
- poly(ADP-ribose) polymerase (PARP): enhances DNA fragmentation
what is the signal that initiates activation of the initiator 9 caspases?
the mitochrondria releases cytosome C which binds to Apaf 9, to turn into the adaptor protein apoptosome and bind to caspase 9 activating it
what is bcl2 function normally and what happens if it gets mutated or overproduced?
its normal function is to stop apoptosis. If it gets mutated, it causes embryonic lethality. In cancer however, there is a mutated where it is over expressed and that allows the cancer to survive
how does bcl2 control apoptosis?
the pro-apotoptic proteins Bax and bak of bcl2 form pores to release of the cytochrome C from the mitochondria making it the regulator of the instrinic pathway
how does the bcl2 mutation cause cancer cells to survive?
the anti-apoptotic bcl2 family is located outside the cell and will inhibit the pro apoptotic cell from forming pores
what is BH3-only and what’s its job
it gets signalled by an apoptosis signal to inhibit the anti -apoptotic bcl2 family so apopotisis can occur
what are IAP and what do they do?
they are inhibitors of apoptosis and they stop the formation of caspases
how are IAPs stopped?
the mitochondria releases SMAC (anti-IAP) to inhibit the IAP
how do nerve cells affect apoptosis
they send survival factors to target cells, if target cells dies then the neuron dies as well
what are the 3 ways apoptosis can be inhibited extracellularly
a survival factor can
- increase the production of the anti-apoptotic Bcl2 family
- inactivate the the BH3- only protein
- inactivate the anti IAPs
how does apoptosis get triggered
by a withdrawal of survival factors (aka tropic factors)
what do the tropic factors do
they activate RTKs and cytokine receptors to trigger PI-3 kinase to the membrane to stop apopotisis
what is the role of the PI-3/Akt pathway
to inactivate pro apoptotic genes
how does PI3 work with Akt to stop apoptosis?
1) PI3 phosphorylates PIP3 so its a docking site for PDK1
2) PDK1 phosphorylates Akt releasing it to phorylate Bad to release an activate apotheosis inhibitory protein
3) apoptosis is stopped
what is the extrinsic pathway of apoptosis?
1) a killer lymphocyte ha a Fas ligand and it binds to the Fas receptor of the target cell
2) this causes conformation change to disc formation of caspases 8
3) the capase 8 gets cleaved and it activates caspase 3 (the executioner caspase)
How is the apoptotic cell cleared?
after the cell dies it shows phosphotidylserine on the extracelluar face which is a signal for phagocyte to come eat it
how does the phosphotidylserine end up on the top excellauar face of the cell
the executioner caspase inactivates flippase (who was keeping it inside) and activates scramblase (who puts it outside) by cutting regulatory portion of both
