White Lecture 5 "Apoptosis" Flashcards
What are the two forms of cell death?
Apoptosis and necrosis
Define necrosis
accidental cell death
dirty way of dying
when it dies, the cell contents leak out. yuck
Define apoptosis
routine controlled cell death that minimizes spread of damage and or inflammation
cell death under physiological conditions
clean way of dying
cell programmed death
What happens to cells when they are no longer needed?
They die
True or false: apoptosis is not important in development of mature forms
FALSE: They are important in development of mature forms
Describe the “phenotype” of apoptosis
- overall shrinkage in volume of cell and its nucleus
- loss of adhesion to neighboring cells
- formation of blebs on surface
- DNA fragmentation
- Cytoskeleton collapses
- nuclear envelope dissembles
- rapid engulfment of dying cell by phagocytosis
Why is apoptosis important in the cell?
Can get rid or any abnormal, non-functional, or dangerous cells
eliminate lymphocytes after destroying microbes
keep liver the right size
DNA damaged cells
What is the marker of apoptosis?
cytochrome c that is released from mitochondria
What is in charge of cleaving DNA into a ladder of fragments in distinctive sizes?
Where do these cleavages occur?
endonuclease
They occur in the linker regions of the nucleosomes
Define caspases
cysteine aspartyl specific protease
proteases that mediate apoptosis; targets the proteins and cleaves them in their sequence where an aspartic amino acid occurs
Describe procaspases
Inactive precursors of caspases
activated by protease cleavage
Describe the activation of caspases
cleaved at specific sites to form large and small subunits which forms a heterodimer then caspases activate them
What are the 2 major classes of caspase?
Initiator and Executioner
Define initiator caspase
initiates apoptosis
Define executioner caspases
destroys actual targets and executes apoptosis
Where do the caspases cleave, target, and what do they attack?
The cleave downstream proteins and inactive endonucleases
Target cytoskeleton
attack cell adhesion proteins
True or false: The caspase cascade it irreversible
TRUE
What are the two apoptosis pathways?
internal and external
What are the internal and external stimuli?
Internal are the abnormalities or DNA and the external are the removal of the survivial factors and proteins of the tumor necrosis facto family
Describe the intrinsic pathway
mitochondrial dependent
cells can activate from inside the cell; responds to injury
translocation of cytochrome c from the intermediate space of the mitochondria
This is released to the cytosol and will bind to the adaptor protein to activate the procaspases
Describe what happens when cytochrome c is released from the mitochondria in the intrinsic pathway
- binds to the procaspase-activating adaptor proteins (Apaf-1)
- Apaf-1 forms an apoptosome which activates caspase-9
- caspase-9 activates downstream executioner caspases
Which caspase is common to both pathways?
caspase 3
Describe the extrinsic pathway
- Fas binds to the Fas Death receptor
- FADD adaptor and the procaspase 8 come to the death effector domain
- trimers are formed that bring the death domains together to from the DISC (death inducing signal complex)
- activates caspar 8 or 10
- Activates downstream executioner caspases
Define decoy receptors
inhibitory protein that restrain the extrinsic pathway;
have a ligand binding domain but no death domain
Define FLIP protein
a protein resembling initiator procaspase with no proteolytic domain
competitive inhibitor against procaspase 8 and 10
prevents apoptosis
Describe the Bcl2 family of proteins
regulate the intrinsic pathway
Bcl2 controls the release of cytochrome c
What are the two types of the Bcl2 proteins?
antiapoptotic and proapoptotic
Define anti-apoptotic
prosurvivial obvs
blocks the release of cytochrome c
has 4 distinctive domains
Define pro-apoptotic
promotes the release of cytochrome c
BH123 and BH3 only
Describe the BH-123 protein in apoptosis
pro-apoptotic
apoptotic stimulus triggers intrinsic pathway
activated and form aggregation in mitochondrial outer membrane and induce the release of cytochrome c then an apoptsome formed by binding to Apaf1
Describe anti-apoptotic Bcl2 proteins
located on the cytosolic of the outer mitochondrial membrane
prevents apoptosis by binding to the pro-apoptotic proteins and prevent aggregation into the active form
Describe the BH3-only protein
cytosolic
translocates to the mitochondria after apototic signal activates it
inhibits anti-apoptotic Bcl2 protein from inhibiting aggregation to relate cytochrome c
PROAPOPTOTIC
What do IAPs do?
Inhibitors of Apoptosis
bind and inhibit caspases
some IAPs add ubiquitin to caspases to mark them for destruction by proteasome
block apoptosis
help with the auto-activating issue
ANTI_APOPTOTIC
What do anti-IAPs do?
released from the mitochondria to block the activity of the IAP’s so that the executioner caspases can be blocked
LIBERATE caspases
What happens in the event that there is excess Bcl2?
development of cancer by inhibiting apoptosis;
B cell lymphoma
What can occur in the event of excessive apoptosis?
heart attacks and strokes
