Cell Signalling 6 Flashcards
(26 cards)
What is apoptosis ?
A process seen in multicellular organisms, by which specific cells are killed and removed for the benefit of the organism
What is the need for apoptosis ?
It maintains homeostatic balance in organisms.
It makes sure we have the right balance of cell proliferation and cell death.
What does too much apoptosis cause ?
Degenerative diseases eg. Alzheimer’s or heart disease
What does too much cell proliferation cause ?
Solid tumours, leukaemia
Why would cells be damaged beyond repair ?
- DNA damage- proteins won’t be able to function properly
- Accumulation of misfolded proteins
- Cells infected by certain viral agents
What are the morphological features of apoptosis ?
- Cell shrinkage
- Chromatin condensation (common shape is a crescent moon through microscope)
- Fragmentation of intracellular contents and membrane blebbing (bubble)
- Formation of apoptopic bodies (ABs)
- Phagocytic ingestion of AB and degration
Why is it important that the plasma membrane maintains its integrity throughout apoptosis?
So that no toxic substances are released, causing harm to nearby cells
What mediates apoptosis in animal cells ?
A family of suicide proteases called caspases
What do we know about caspase structure and function? How is it activated ?
It has cysteine as the active site.
It cleaves target proteins at specific aspartic acids .
Activated by proteolytic cleavage at own aspartic residues.
What are initiator caspases ?
They undergo autocleavage.
Activated other caspases
What are effector caspases ?
Activate other effector caspases after cleavage by initiator caspase.
Cleave cellular caspases
What is the key ‘engulf me’ signal on the surface of apoptopic bodies ?
Phosphotidylserine (PS)
What is scramblase ?
The action of caspases activated the enzyme scramblase which mediates PS flipping, to move them to the outer leaflet of the plasma membrane to be engulfed.
What are examples of intrinsic apoptosis pathways ?
- DNA damage
- Protein misfolding
- Lack of tropic factor-induced signalling
What is another name for the intrinsic pathway ?
Mitochondrial pathway
How is the intrinsic apoptosis pathway activated?
If signalling molecules allow the release of cytochrome C from the mitochondria into the cytosol
What are pro-apoptopic molecules? Name some examples
Molecules that promote apoptosis
Eg. BAX, BAK, BAD
What are anti-apoptopic molecules? Name some examples
Preventing apoptosis
Eg. BCL-2, BCL-Xl
How does BCL-2 work ?
It inhibits apoptosis by preventing the release of cytochrome C from the mitochondria by blocking action of BAX and BAK
How do BAX/BAK work ?
They promote apoptosis by forming channels in the outer mitochondrial membrane to allow cytochrome c release
What is procascape?
A molecule of caspase that hasn’t been activated yet, it cannot cut anything
How do growth factors or survival factors suppress apoptosis ?
By:
1. Increasing the transcription and translation of anti-apoptopic molecules
2. Signal transduction kinases which are activated by stimulation of trophic receptors, phosphorylate and inactivate pro-apoptopic molecules
What is the initiator caspase used in the extrinsic pathway ?
Procaspase 8
What is the initiator caspase used in the intrinsic pathway ?
Procaspase 9
