Term
Apoptosis - self killing
vs
Autophagy - self eating |
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Definition
•Apopotosis - normal cell response to physiological signals
–No lysis. Stealth process. The lack of disturbance to tissue retarded the recognition of apoptosis as an important process.
•Autophagy - normal cell response to nutrient stress.
–Protects cell from death
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Term
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Definition
–1) cell death
•Chromosome breakage, nuclear fragmentation
•Expression of cell surface ‘death’ signals
•Cell blebbing and fragmentation
–2) Phagocytosis of corpse by neighboring cells
•Response to ‘death’ signals
•Activation of cytoskeleton to engulf cell fragments
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Term
Apoptosis is required for..... |
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Definition
•Development:
–General morphological development- tissue sculpture
–Nervous system
•Immune system development
–elimination of cells
•Maintenance of cell homeostasis
–Immune response, stress response, Cancer.
–Highly regulated. Too little or too much can lead to disease.
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Term
Human Analogs of C. Elegans Ceds |
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Definition
worm Ced-9 = human Bcl-2
worm Ced-3 = human capsase
worm Ced-4 = human Apaf-1
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Term
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Definition
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•11 human caspases
–Some are involved in apoptosis (2,3,6,7,8,9 and 10)
–Others are required for cytokine maturation.
•caspases translated as inactive zymogen (pro-caspase).
–activated by proteolysis
–activation is key to regulation
Active caspase contains two peptides. Both are products of caspase zymogen
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Term
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Definition
–Initiator caspases. auto-activate themselves under certain conditions. Have an extended amino terminus Caspases 2, 8, 9, and 10
–Effector/Executioner caspases. require activation by another protease (usually another caspase). Have a short amino terminus. Caspases 3, 6, and 7
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Term
Activation of initiator caspases |
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Definition
-by dimerization and by proteolysis
-are activated by the assembly of the procaspases into large complexes- a platform for autoactivation
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Term
Two major platforms of activating Initiator Caspases
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Definition
Extrinsic pathway
Death receptor pathway
TNF receptor mediated
Fas/FasL as example
Intrinsic pathway
Mitochondrial pathway
Membrane permeabilization
Release of cytochrome c
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Term
Intrinsic Apoptosis pathway |
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Definition
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•Triggered by change in mitochondrial permeability.
–induced by genetic or toxicological damage or deprivation of growth factors.
•Release of cytochrome c from mitochondria activates the apoptosome.
–multisubunit complex formed from Apaf-1 and cytochrome c.
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Term
Other proteins released from mitochondria play a role in apopotosis. |
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Definition
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•SMAC (second mitochondrial activator of caspases) (Diablo in Drosophila).
–Sequesters caspase inhibitors, IAPs
(XIAP)
•Originally identified as a protein that inhibited apoptosis in insect cells
• Large family of related proteins that bind to surface of caspases and inhibit catalysis
•Some have RING finger domains that act as ubiquitin ligases. Induce proteolysis of caspases
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Term
AIF (apoptosis-inducing factor) |
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Definition
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-released from the mitochondria
-conserved oxoreductase
–Isolated as a factor that induced caspase-independent chromatin condensation and nuclear fragmentation in isolated nuclei but AIF-/- cells are sensitive to apoptosis-inducing agents, suggesting that AIF may not have a role in apoptosis
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Term
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Definition
–May act in combination with CAD
(caspase-activated deoxyribonuclease)
Inactivation of C.elegans Endo G protects cells from pro-apoptotic effects of weak Ced-3 mutants |
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Term
Mitochondrial permeability regulated by Bcl-2 family members |
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Definition
•Key to control of intrinsic pathway is regulation of mitochondrial permeability by a family of related proteins (Bcl-2 protein family).
•Bcl-2 protein family consists of 24 members in humans
•Three basic classes:
–anti-apoptotic proteins (Bcl-2, Bcl-XL)
–pro-apoptotic BH123 proteins. (Bax, Bak)
–pro-apopotic BH3-only proteins (Bid, Bad, Bik, Puma, Noxa)
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Term
Pro-apoptotic Bcl-2 members facilitate.... |
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Definition
-forming a pore in the outer Mitochondrial membrane.
•Pro-apoptotic Bcl-2 members (Bax/Bak) facilitate pore formation in the outerMitochondrial membrane.
–allows the escape of cytochrome c and other pro-apoptotic factors.
•Anti-apoptotic Bcl-2 members(Bcl-2) reside in the mitochondrial membrane and antagonize Bax/ Bak
•BH3- only proteins (group III) act by antagonizing anti-apoptotic Bcl-2 proteins or activating Bax/Bak
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