theme 3- CB17 Cell death Flashcards
What is the role of cell death in development?
- remove or remodel tissues (formation of digits)
- formation of complex tissues e.g. CNS
What is the role of cell death in the cell cycle?
it is the end of the cell cycle as a result of
1) stressed /damadge cels: DNA damadge or build up of misfolded protein
2) Removal of infected cells: killing by cytotoxic T cells
3) control cell numbers: e.g. useless or dangerous lymphocytes in the thymus- find out what the thymus is
4) During development
a) What is the molecular mechanism for cell apoptosis?
b) In more detail what are the function of the enzymes?
a) procaspases cleaved = active form called caspase protease
Caspases activate other caspases (making pathway self-amplifying and irreversible) or carry out function.
b) Functions of caspases:
1) Cleave other caspases as part of activation cascade
2) cleave nuclear lamins (structural proteins of the nucleus which leads to nuclear fragmentation)
3) activate DNase which cut DNA into fragments
4)Cleave cytoskeleton= cell detaches from neighbours, loses contact with ECM and cell rounds up
What are the 2 forms of cell death? When do they occur? how does the cell die?
- necrosis- acute injury, cell swells, bursts (lysis) and contents is released into tissues = inflammatory response = more damadge
- apoptosis- programmed cell death where suicide pathway is activated
Explain what occurs during cell apoptosis:
1) cytoskeleton collapses= Cell shrinks and collapses
2) Surface bulging develop
3) DNA and nucleus fragments form (which is why electrophoresis results in multiple bands the further along apoptosis)
4) Membrane changes trigger phagocytosis
5) cell engulfed and digested cleanly
What external factors supress apoptosis?
1) survival factors, mitogens, & growth factors
2) contact with the ECM (remember intergrin dimers embedded in membrane (attached to actin via adapter proteins on cytosolic side) are attached to fibronectin which is attached to collagen fibril)
What external factors activate mitosis?
1) hormonal signals
2) Cytokine signals (Tumour nekrosis factor- family e.g. Fas-L)
3) Direct signal from contacting cell
What is the role of survival factors in the formation of nervous tissues?
a large number of cells are produced and grow outwards, only those whos axon has suffiecient contact with target cell survive, as these receive signals from survival factors secreted by nerve cells.
What are the regulators of apoptosis? What are the 2 sub groups +e.g.s
Bcl-2 family
Promotors of apoptosis: Bax, Bad, Bak
Inhibitors of apoptosis: Bcl-2, Bcl-X
What are the promoters of apoptosis?
How do they work?
Bax, Bak and Bad
they activate caspases and the formation of the apoptosome (protein that activates initiator caspase)
- Bax and Bad do this by inducing cytochrome C release from the mitochondria
What are the inhibitors of apoptosis?
Bcl-2, Bcl-X
balance regulates susceptibility to apoptosis
How does mitochondrial injury result in apoptosis?
1) cytochrome C leaks from cell membrane
2) Cytochrome C in cytosol activates caspases
3) Caspase cascade =apoptosis
Name one inhibitor of apoptosis and state how it works:
Bcl-2 inihibits apoptosis by stopping Bax and Bak from activating release of cytochrome-c
How does p53 cause apoptosis when DNA damdge cannot be repaired?
trigger apoptosis by stimulating Bax
