Cours 9 - Cell Cycle III: Apoptosis Flashcards
What is the difference between apoptosis and necrosis?
Necrosis comes from the injury of a cell.
- ↓ ATP & NA+/ATPase activity followed by lysis
Apoptosis: programmed cell death
Why do apoptosis occurs?
- Balance of cell division with death
- Avoids the disadvantages of necrosis
What are the structural changes that occurs during apoptosis?
Step 1
- Chromatine condense
- cytoplasm shrinks
Step 2
- nucleus fragment,
- lost of adhision,
- DNA laddering (fragmentation of the genetic material),
- blebbing (looks like a bubble),
- cell fragmentation.
- The cell membranne change and loose it’s symetry.
- Negative charged phosphatidylserine are exposed outside the cell
- The cell is then marked for phagocytosis by a macrophage
Step 3
phagocytosis
What are the 2 apoptosis pathway and how to we differentiatte them?
intrinsic
extrinsic
Is the signal comming from inside or outside the cell
in 1 sentence for each, describe:
- What are caspase
- how they work
- how they are activated
They are proteases that cleave essential proteins.
This enzyme has a cysteine residue at its catalytic site and cleaves other protiens at an aspartate site.
they phosphorylate each other
What essential protein do caspase cleave?
- Protein Kinases
- Lamins
- Cytoskeleton
- CAD = caspase-activated DNAse
What does the cleavage of protein kinase by caspase does in the cell?
Particularly, the cleavage of FAK (focal adhesion kinase) causes the cell to loose adhesion.
FAK is a transmembrane protein that allows a cell to adhere to a substrate in the extracellular matrix
What does the cleavage of Lamins by caspase does in the cell?
Lamins are important for structure of the nuclear membrane
the cleavage of lamine leads to:
- the degradation of the nuclear lamina
- causes the shrinkage of the cytoplasm
- the fragmentation of the nucleus.
What does the cleavage of the cytoskeleton by caspase does in the cell?
- It induces changes in cell shapes
- cell cannot go locomotion
- no more division
What does the cleavage of CAD by caspase does in the cell?
CAD = caspase-activated DNAse
CAD will become active and fragment the DNA
Describe procaspase activation of caspase (excluding caspase cascade)
Normally, Initiator (or “pro”) caspases are inactive
An apoptotic signal triggers assembly of adaptor proteins that activate procaspases.
Those adaptor protein bring procaspases closer together so that they can cleave each other at the aspartate site. That protolitic interaction (cleavage) is what renders procaspase active.
Procaspase will then activate caspase by cleavage.
then caspases will activate cascade that will lead to apoptosis
What are the 2 types of caspase?
initiator and executionor
describe the intrinsic pathway apoptosome formation of caspase
- Initiated by DNA damage or loss of survival factor.
- An intracellular death signal initiates caspase cascade and cell death.
- Apoptotic signal activates Bcl2 family proteins (e.g. Bax) to form aggregates in outer mitochondrial membrane. This forms a pore releasing cytochrome C
- Bcl-2 inhibits apoptosis (is deactivated)
- Bax and Bak act on mitochondria and release cytochrome c.
- Activation of Apaf1 by cytochrome c
- assembly of Apaf1 through it’s CARD domaine in apoptosome
- recruitment of caspase-9 through CARD domaine
- Caspase now is now active and will activate executioner caspase
Describe the caspase extrinsic signal pathway
- Procaspase activation triggered from outside the cell.•FAS death receptors is expressed on the outside of the cell
- Extracellular signal (Fas ligand) activates death receptor (Fas protein).
- Recruitment of FADD adaptor protein and caspase 8
- Caspase 8 is active and activates executionor caspase
Describe how survival factor blocks the intrinsic apoptosis pathway
- Survival factor links to receptor
- signal activates PKB
- PKB phosphorilate BAD which causes it to release Bcl-2
- active Bcl-2 now inhibites cytochrome C release from mitochondria
In parallele:
- Survival factor signal inhibites bax preventing it from releasing cytochrome C from mitochondria
If DNA damage:
- Stable active P53 will activate bax
During the Developpement of the Nervous System, a lot of nervous cell undergo apoptosis. Why?
Nerve growth factors are also survival factors
it is released by the target cell until it is linked to a nerve
Cell death matches the number of nerve cell to the number of target cell because tou need one nerve cell per target cell. The extra will go through apoptosis.
