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C2-21 Apoptosis I : Morphologic Features
Cell Death
14
Biology
Professional
10/19/2010

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Cards

Term

 

Apoptosis - self killing
vs
 
Autophagy - self eating

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

Term

 

 

 

Two parts of Cell Death

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

Term




Apoptosis is required for.....

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. 

Term

 

 

 

Human Analogs of C. Elegans Ceds

Definition

worm Ced-9 = human Bcl-2

 

worm Ced-3 = human capsase

 

worm Ced-4 = human Apaf-1

Term

 

 

 

caspases

Definition

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

 

Term

 

 

 

procaspases

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

Term



Activation of initiator caspases

Definition

-by dimerization and by proteolysis


-are activated by the assembly of the procaspases into large complexes- a platform for autoactivation

Term

 

 

 Two major platforms of activating Initiator Caspases

Definition

Extrinsic pathway

Death receptor pathway

TNF receptor mediated

Fas/FasL as example


Intrinsic pathway

Mitochondrial pathway

Membrane permeabilization

Release of cytochrome c

Term




Intrinsic Apoptosis pathway

Definition

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.

 

Term

 

 

Other proteins released from mitochondria play a role in apopotosis.

Definition

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

 

Term

 

 

 

AIF (apoptosis-inducing factor)

Definition


-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

 

Term



 

Endonuclease G. 

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

Term



Mitochondrial permeability regulated by Bcl-2 family members

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)

Term




Pro-apoptotic Bcl-2 members facilitate....  

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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