apoptosis Flashcards
(19 cards)
Hallmarks of Necrosis (4)
- cell rupture 2. tissue injury 3. inflammatory response 4. takes hours
Hallmarks of Apoptosis (4)
- cell destruction w/o rupture 2. no tissue damage 3. phagocytosis of cell corpses (apoptotic bodies) 4. takes minutes
Examples of apoptosis in the body
- embryonic development 2. death of immune cells 3. death of cells induced by cytotoxic T cells 4. hormone-dependent involution in adults
What happens to the cell in apoptosis?
- cell seize decreases 2. chromatin condenses 3. DNA is fragmented 4. blebbing of plasma membrane 5. phagocytosis (all 5 steps take about 1 hour)
What is the difference between intrinsic and extrinsic mechanisms of apoptosis?
INTRINSIC (cell suicide) - stimulated by withdrawal of growth factors or cytokines, by radiation or radical-induced damage EXTRINSIC (cell murder) - stimulated by cytotoxic T cells via death receptor or Fas/Fas-ligand interaction
5 general constituents of the apoptotic pathway
- signal 2. adaptors 3. regulators 4. caspases 5. scramblase/phagocytosis
Intrinsic apoptotic signal
withdrawal of growth factors/cytokines or radiation damage, hypoxia, thermal damage
Extrinsic apoptotic signal
death receptor activation or tumor necrosis factor receptor activation (Fas receptor - Apo1 or CD95)
Intrinsic apoptotic adaptors
Apaf-1 (Pro-apoptotic protease activating factor -most common) - recognizes signal and can bind many caspases so that they can cross proteolyse and activate each other
Extrinsic apoptotic adaptors
FADD (Fas-assocaited w/ death domain) - aggregated caspases when receives signal
Intrinsic apoptotic regulators
Bcl-2 family - coiled coil interactions between alpha-helical BH domains to form complexes that can either inhibit or promote cell death - balance is IMPORTANT
Bcl-2 family of proteins - pro-survival
Bcl-2 binds Apaf-1 and prevents it from activating caspases, also can bind and inhibit pro-apoptotic members (Bax) in mitochondiral membrane
Bcl-2 family of proteins - pro-apoptosis
Bad and Bax. Bad binds Bcl-2, which liberates Bax to form pores in the mitochondrial membrane for cyctochrome C to get out
Extrinsic apoptotic pathway
Types of Caspases
- initiating capases (Ced8 & 9) activated by aggregation 2. Execution caspases (Ced 3, 6, & 7) carry out cleavage of proteins inside the cell
How do caspases work?
They are proenzymes, they are synthesized in the inactive form and must be cleaved of their autoinhibitory domain to be active. They are specific, so protein degredation is controlled and precise
How do cells signal phagocytosis?
enzyme scramblase moves phosphatidyl serine to the outer leaflet of the plasma membrane, which is recognized by CED1 receptor on macrophages
Intrinsic apoptotic pathway
What happens when apoptosis doesn’t work?
- suppression = cancer (example - p53 is mutated and can’t trigger apoptosis) 2. excess = neurodegenerative diseases
