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20 Cards in this Set
- Front
- Back
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How is apoptosis different from necrosis? How does DNA look? How long does it take? How many cells involved?
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Apoptosis doesn't involve the leakage of cellular contents into the cellular matrix to damage other cells. Apoptotic cells emit signals which get them rapidly phagocotyzed.
Apoptotosis happens on single cells, not groups (in necrosis) It's rapid (necrosis can take days) precise cleavage of DNA (see large going to small fragments) - necrosis results in random smear fragments. Apoptotis = no inflamation, no collapse of tissue structure (opposite of necrosis) |
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If looking on FACS, how can you detect apoptosis?
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Sub G1 shoulder or peak of DNA, containing a low amount of DNA. This is due to breakdown of the nucleus and the vessicle-ization of the DNA.
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What are the 4 steps of apoptosis?
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A signal (minus growth factors, erythropoetin - in absence, the progenitor undergoes apoptosis radiation, etc)
Regulatory control proteins execution of cascade phagocytosis |
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What are the 4 signals that can start apoptosis?
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DNA damage
growth factor withdrawl death receptor activation cytotoxic t-cell activity |
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What is P53? how does it work?
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If DNA damage detected by ATM, p53 gets stabilized. if damage is manageable, it induces CDKi's to halt cell division and begin repair.
if it's too bad, it induces Bax (apoptosis) and suppresses Bcl-2 (apoptosis) |
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If DNA damage is detected, what happens to P53?
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P53 is normally degraded by MDM2. If DNA damage, ATM induces Chk2 to phospho P53, keeping it more stable. It can then go to work. Also, ARF (transcribed by p53) degrades MDM2. Arf = p53 stabilizer.
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Without growth factors, what pathway turns off?
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PI3/AKT/PkB pathway (which is ANTI-apoptotic) turns off. Bbl-2 off, Bad on, bax on, cytochrome c leaks out.
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Tell me about death domains
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Fas receptor binds its ligand (fasL or TNFa), trimerizes, activates capsase 8 = apoptosis.
Receptor = FADD (fas-associated death domain) |
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Cytotoxic T cells - what factors do they release that induce apoptosis? how do they work?
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Granzyme and perforin. Perforin makes channels in the target that granzyme can get through, it can induce capsase (no bax/bad/BCL-2)
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Name some proteins in the BCL-2 pathway. Are they pro or anti apoptotic?
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Pro-apoptotic: bax, bad, bim
anti: bcl2, bcl XL |
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How do growth factors keep act through the BCL-2 pathway?
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GF's activate PI-3/AKT/PKB, which phosphorylate BAD (keep it sequestered).
W/out, Bad free - binds up BCL-2, which releases Bax - Bax opens channels in mito, release cytochrome C, interacts with APAF1 = caspase activation = apoptosis. |
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What are IAP's? How are they inactivated?
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Inhibitors of Apoptosis - effectors floating in cytosol, binding up capsases.
Injure mito. release SMAC/DIABLO - bind up IAP's, free capsase = apoptosis. |
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What is forkhead? What inhibits it?
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Pro-FasL (death domain) TF.
The PKB/IP3/ATK pathway inhibits forkhead. |
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How is capsase activated?
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Capsase is always a ZYMOGEN - pre-capsase. Cyrochrome C release activates APAF1 (gets an ATP hydrolyzed) - binds into 7-subunit apatosome - this cleaves Capsase 9, activate other capsases.
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How can apoptosis be initiated without a mitochondria?
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Use a death cell receptor (fasL) - activate pro-Capsapse 3, activate it.
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How is capsase amplification achieved?
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Capsease 8/9 can activate lots of other capsases, each with its own way of promoting apoptosis.
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What are 3 structural changes that signal for phagocytosis?
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Formation of THROMBOSPONDIN binding sites
Exposing side chain sugars PS - phosphatidyl serine exposure. |
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What mutation should follicular B cell lymphoma make you think of?
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BCL-2 (b-cell lymphoma!) - gets way turned up, prevents apoptosis.
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How do viruses keep cells from apoptosis?
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Mimic BCL-2, sequester Bad, keep cell alive. Also, adenoviruses make E1B, inhibits P53 to prevent apoptosis.
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What do heart attacks have to do with apoptosis?
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Ischemic stress may induce apoptosis in surrounding cells (see increased capsase 9/3)
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