Apoptosis Flashcards
What is apoptosis?
A programmed form of cell death which is tightly regulated
How can apoptosis by initiated?
It can be initiated by stimuli from within the cell (such as DNA damage or protein misfolding)
It can also be initiated by signals from outside the cell
Give examples of physiological apoptosis
- embryogenesis
- cell turnover
- hormone withdrawl (in hormone dependant tissues)
- self reacting lymphocyte elimination
- death of neutrophils after acute inflammation
Give examples of pathological apoptosis
- cell death in certain infections
- pathological atrophy in parenchymal organs
What are the morphological changes which occur during apoptosis?
Cell shrinkage
Chromatin condensation
Formation of cytoplasmic blebs and apoptotic bodies
Lastly phagocytosis of apoptotic bodies GONE
Why does apoptosis not elicit the inflammatory response?
The plasma membrane remains intact in apoptosis and the contents of the cell does not spill out and trigger inflammation as in necrosis
Describe the discovery of apoptosis by Sulston during his studies with C. Elegans
Sulston calculated that the nematode, throught developement, should have produced 1090 cells. However, when counting cells of developed C. Elegans they would have 959 cells. Hence there must have been a form of cell death (not necrosis) which played a fundamental physiological role in development
Describe the genes of Apoptosis
10-20 genes control apoptosis, highly conserved throughout specis
What is the key step in the activation of apoptosis (both in intrinsic and extrinsic pathways)?
The activation of Caspase 8
Describe the chain of events after the activation of Caspase 8
- Activation of BCL2 members (e.g. BID) on the mitochondrial membrane, causing the formation of channels
- Efflux of cytochrome C from the mitochondia (via channels formed)
- Cytochrome C together with Apaf-1 form the apoptosome
- The apoptosome activase pro-caspase 9 into active caspase 9
- Active caspase 9 can activate caspase 3 - which is the ultimate effector of apoptosis
Who is the ultimate effector of apoptosis?
Caspase 3
Under which other circumstances can cytochrome C be released from the mitochondrion?
When Ca++ concs are high
In the presence of free radicals
Why does apoptosis have a fundamental role in cancer prevention?
Apoptosis eliminates cells with damaged DNA
Note: mutations in apoptosis genes lead to tumour growth
Which pathologies may disregulated apoptosis lead to?
Neurodegenerative disease
Ischemic Injury
Cancer
Autoimmune disorders
