Lecture 10: Cell death Flashcards
how do cells die?
Most die through:
- Necrosis
- Apoptosis
- –‘falling of leaves’
- –programmed cell death
- – cell suicide
-More than one mechanism may be involved in the death of a cell
necrosis is characterised by
- Loss of cell components by lysis
- Inflammation
- Autolysis
- Debris (pus)
- (Calcification)
–uncontrolled cell death?
Apoptosis characterised by
- Shrinkage
- Nuclear breakdown
- Phagocytosis
- Requires protein synthesis (cycloheximide-sensitive)
–controlled cell death? (autophagy)
necrosis is associated with
- physical damage
- -gut epithelium
- -drying e.g. nasal epithelium
- -trauma e.g. cuts and burns
- infections
- acute toxicity
- acute hypoxia / ischaemia
- rapid loss cell energy
apoptosis is associated with
- Developmental cell loss
- Senescence
- –Hayflick number
- Chronic toxicity
- Removal of growth factors
- Detachment from substrate
- –(Anoikis - homeless cells)
is it just Necrosis or apoptosis ?
both can occur in the death of a cell.
Brain ischaemia
-cells in the middle die through necrosis
-cells at the edge die through apoptosis
2 mechanisms of apoptosis
- in development
- in the haematopoietic system
developmental apopstosis:
death is common
- metamorphosis e.g. tadpole - frog
- digit formation
- nervous system
CED genes, how many
10+ genes
- recognition to engulfment (most)
- 4 key: RGL-1, Ced 3, Ced 4, Ced 9
decreased Ced 3/4 gives
excess adult cells
decrease Ced 9 gives
massive cell death
ced genes are known as
pro- and anti- apoptotic genes
EGL-1 blocks
Ced 9
Ced 9 blocks Ced 4,
Ced 4 activates Ced 3, Ced 3 triggers cell death
CED genes: mammalian homologues:
- EGL-1 and BH3-only proteins
- Ced 9 and Bcl-2
- Ced 4 and APAF-1
- Ced 3 and the caspases
Caspases are
the executioners of cell death
- no caspase activity, no apoptosis
