L15- Cell death Flashcards
What is necrosis?
Accidental cell death, or death by injury
What is apoptosis?
Programmed cell death, or cell suicide
What happens first to the apoptotic cell?
It’s phagocytosed, usually by macrophages
What does the apoptotic cell release?
ATP which attracts macrophages
What signals for the macrophage to eat a cell?
Changes to the apoptotic cell plasma membrane liipid composition
Why is apoptosis needed?
To remove: Unnecessary/obsolete cells (eg tail) Excess cells Harmful cells Day to day housekeeping (match growth with cell death)
If a cell has DNA or other damage what happens?
Cell produces p53-
blocks the cell cycle if the damage is minor
OR triggers apoptosis if there’s major damage that can’t be repaired
How do cells die in Heart attack or stroke?
1st wave of cell death by necrosis
2nd wave of massive apoptosis (lots of factors released when lack of oxygen-> kills next cells)
What is apoptosis mediated by?
An intracellular proteolytic cascade. With caspases. Caspases have cysteine in active site and cleave targets at specific aspartate residues.
How is the first caspase activated?
Adaptor proteins bring together 2 procaspase moleecules by cleavage-> turns to on active caspase molecule.
What does the first caspase then do? (after being activated)
It cleaves and activates other caspase molecules causing a cascade.
So once it starts, the cell deconstructs itself completely really fast.
Which proteins do caspases cleave?
Specific subset- mostly structural proteins e.g. nuclear lamins, cytokeratin.
What are nuclear lamins?
Filament underlying the nuclear envelope, forming the nuclear lamina
What are the 2 pathways that trigger apoptosis?
- Intrinsic pathway- cell damage e.g. DNA
2. Extrinsic pathway- extracellular singals-> removal of survival factors receipt of death signal.
How does the instrinsic pathway recruit caspases?
If there’s an apoptotic signal, cytochrome C is released and recruits caspases outside the organelle.