Apoptosis Flashcards
Summarise apoptosis
Condensation and segmentation of nuclei with fragments of chromosomal DNA into nucleosome fragments
Condensation and fragmentation of the cytoplasm with subsequent phagocytic clearance
The cell surface membrane also flips phosphatidylserine dto the outer leaflet to promote phagocytosis and forms blebs
Compare necrosis to apoptosis
Apoptosis - from external or internal signals, energy dependent, single cells, cells shrink and are engulfed, normally no inflammation
Necrosis- ischemia/toxins/radiation, groups if cells, cells swell and burst, marked inflammation
Describe the mechanism of apoptosis
Bcl2 family- antagonises the action of caspases and Apaf1 and therefore apoptosis- Bcl2 pro-survival, Bax and BH3 only family pro-apoptosis
Caspases- caspase1- interleukin 1b converting enzyme (ICE), initator caspases (8,9,10,12), which cleave and activate the executioner caspases (2,3,6,7) degrade cell cycle regulators, DNA (via DNase), DNA repair components, cell signalling and adhesion molecules, cytoskeleton
Mitochondria- changes on mitochondria membrane potential releases cytochrome C which forms a cokmpkex with Apaf1 dimer and procaspase 6 to activate caspases 9 which activates the caspases cascade, Bcl2-BH3 heterodimer and Bax homodimers on the mitochondrial membrane cause the release of cytochrome C
Apaf1 and the apoptosome- Apaf1 is a scaffold protein that forms the apoptosome which recruits AMD processes caspase 9 now the complex can activate executioner caspases
What is the difference between the intrinsic and extrinsic pathways to apoptosis?
Intrinsic- mitochondrial response to apoptotic signal
Extrinsic- death ligand binds to death receptor to activate the caspase cascade eg. Fas and FasL recruit FADD activate caspase 8 and 10
How do cell stress signals activate apoptotic pathways?
DNA damage activates p53 which can lead to the activation of the caspases cascade by the mitochondria and cytochrome C
What is the relationship between cancer and apoptosis?
Apoptotic pathways are suppressed in cancer and survival pathways are activated
Cancers can be treated by activating apoptosis
What is autophagy?
Has roles in: Antigen presentation Survival during short term starvation Organelle turnover Protection against metabolic stress and DNA damage Clearance of aggregate prone proteins Regulation of cell size Longevity Programmed cell death Defence against intracellular pathogens FoxO3, PTEN, reactive oxygen species, GTPase and low ATP act to promote autophagy Ra's, PI3, Akt, mTOR act to promote autophagy
Describe autophagy in cancer
Pro-tumour- escape from stress, tumour cell fitness, treatment resistance, dormancy
Anti-tumour- inhibits chromosomal instability, oxidative stress, inflammation and promotes senescence
