Apoptosis Flashcards
What are the modes of cell death
Necrosis
Apoptosis
Autophagic cell death
Cornification
What are the types of apoptosis we care about today
Intrinsic
Extrinsic
There are 12 but we’re not doing them all. Thank god.
How is apoptosis pronounced
Trick question. No one cares. Don’t be pretentious
Why do cells undergo apoptosis
To allow for proper development - fingers and toes, nerve connections
Allow for tissues growth and regression in adults - remodeling, return to original size
Remove cells that threaten organism (DNA damage, viral infection, immune system homeostasis)
Morphologic changes of apoptotic cells
Cells shrink
Chromatin aggregates
Nuclear envelope breaks up
Blebbing of cell surface
Separation of cells into membrane-bound bodies
Engulfed by phagocytes/macrophages
Is there an immune response with apoptosis
No
How can apoptosis be seen with microscopy (what are the signs)
Relocalization of cytochrome c from mitochondria –> cytoplasm
Can fluorescently label phosphatidylserine (eat me signal)
How can apoptosis be seen with gel electrophoresis
DNA ladder of 180bp caused by internucleosomal DNA cleavage
How can apoptosis be seen using enzymatic assays
Caspase protease activity measured
What are the extracellular signals that induce apoptosis
Increase in bone morphogenic proteins (stimulate digit development)
T-cell clearance - death ligands
Lack of survival factors
What are intercellular signals that induce apoptosis
Increased levels of cellular oxidant
DNA damage –> increased levels of p53 protein
What do both apoptotic pathways result in (not the end result, a common step)
Activation of caspase cascade
What initiates the extrinsic pathway
Death receptors
How do cell death receptors contribute to apoptosis
Transmembrane proteins that bind death ligands (such as TNF)
Result in death-inducing signaling complex (DISC)
which includes death receptor, FADD protein, and initiator caspase
What are caspases
Proteases, synthesized as zymogens (inactive precursors), activated by proteolytic cleavage
What are the tyopes of caspases
Initiator
Executioner
Initiator caspases:
Closely linked to apoptotic signal, cleave and activate executioner caspases
Executioner caspases:
Cleaves proteins in cell (cytoskeletal, nuclear)
Run down of the extrinsic pathway
Extracellular signal –>
Binds to death receptor –>
DISC formation –>
Procaspase cleaved to form active caspase –>
Caspase cascade –>
Executioner caspases activated –>
Destruction of cellular proteins
Who initiates the intrinsic pathway
BcI-2 protein family
What are the forms of the the Bcl-2 protein family & what do they do
Anti-apoptotic - prevent protein release from the mitochondria
Pro-apoptotic - enhance protein release from the mitochondria
Who is in the ‘live’ Bcl-2 group
Bcl-2
Bcl-xL
l = live
Who is in the die (Apoptosis Inducer) Bcl-2 group
Bax, Bak, Bad, Bid, Bim, Puma, Noxa
a & i = apoptosis and die
How does Bcl-2 prevent apoptosis
anti-apoptotic Bcl-2 prevents oligomerization of pro-apoptotic Bcl-2 family proteins (Bax, Bak)
