Apoptosis Flashcards
1
Q
key features of necrosis
A
- triggered by sustained ischemia, physical, or chemical trauma
- cells swell, organelles damaged, chromatin randomly degraded
- cells lyse, organelles destroyed
- leads to inflammation
2
Q
key features of apoptosis
A
- triggered by specific signals that activate certain genes
- cells shrink, organelles are intact, chromatin degraded systematically
- membrane blebs, cell contents retained
- cells are phagocytosed
3
Q
classes of inducers of apoptosis
A
- physiologic
- damage-related
- therapy associated
4
Q
modulation of apoptosis
A
Bcl proteins (intrinsic only)
5
Q
executioners of apoptosis
A
-caspases followed by endonucleases
6
Q
-physiologic inducers of apoptosis
A
- TNF-a
- FasL
- growth/survival factor withdrawal
- glucocorticoids
7
Q
damage related activators
A
- viral infection
- heat shock
- toxins
- tumor suppressors
- oxidants/free radicals
8
Q
therapy associated activators
A
- UV/gamma radiation
- chemo
9
Q
Bcl family proteins
A
- both pro and anti apoptotic
- ratio determines if the cell will live or apoptose
- these work exclusively through the intrinsic pathway via the mitochondria
- antiapoptotic Bcl: prevent phosphorylation of channel proteins on the mitochondrial membrane, inhibiting the release of cytochrome c
- pro-apoptotic Bcl: phosphorylates channel proteins on the mitochondrial membrane, opening the channel and allowing cyt c to leak out into the cytoplasm
10
Q
TNF-a and Fasl
A
- both mediate the extrinsic pathway
- upon binding their receptor on the cell surface, the caspase cascade is initiated within the cell
11
Q
intrinsic pathway steps
- stimulus
- intracellular mech
A
- stimulated by withdrawal of growth factor or hormones
- pro-apoptotic Bcl proteins phosphorylate channel proteins on the mitochondria
- this allows cyt c to leak out into the cytoplasm
- cyt c then intiates the caspase cascade
- cyt c also causes DNA damage, causing a build up of p53 which is another pro-apoptotic protein
12
Q
extrinsic pathway steps
A
- mediated by death receptors: TNF-1 and FasR
- TNF-a binds to its receptor on the cell membrane
- on the intracellular side of the TNF-ar, the caspase cascade is initiated
13
Q
Fasl and immunological privilege
A
- the cap beds in the eyes and the testis are immunologicaly privileged sites
- endothelial cells in these vessels express FasL, so that when leukocyts come through the vessel (which all express FasR) they will be triggered to initiate apoptosis so they do not create an inflammatory response
- note: if you express, FasL then you are fine but if you express FasR then you are at risk
14
Q
caspase 3
A
- both pathways result in a large amount of activity of this protein
- chief executioner of the cell
15
Q
role of caspases
A
- activate endonucleases which cleave DNA in linker regions between nucleosome
- cleave cytoskeletal proteins resulting in the formation of blebs (membrane bound cytoplasmic buds containing intact organelles)
