Flashcards in 31_Apoptosis Deck (22)
What results in inflammation due to necrosis?
cells die and release intracellular contents into tissue/bloodstream; releases antigens not seen as "self" and activates immune response
What are two diseases that can involve inappropriate (excessive) apoptosis?
AD & PD
How is apoptosis required in mammary glands?
plays a role in the formation of epithelial ducts of mammary gland
required for elimination of secretory cells @ weaning
How is an apoptotic cell characterized on EM?
blebs (cellular contents not released, but maintained in apoptotic bodies)
What provides a phagocytosis signal in an apoptotic cell?
movement of phosphatidylserine from the inner leaflet to the outer leaflet of the PM
Briefly describe the morphological changes in an apoptotic cells (sequential order).
1) shrinkage of cell & nuclear volume
2) loss of adhesion to neighbouring cells
3) bleb formation
4) DNA, chromatin, nuclear, cellular fragmentation
What protein kinases do caspases cleave?
>12 of them, including FAK, PKC, Raf 1 (MAPKKK)
What is the consequence of lamin cleavage by caspases?
disassembly of nuclear envelope
What proteins do caspases activate? What are their functions?
endonuclease (cuts between nucleosomes)
DNAse (cleaves DNA)
What groups of proteins do caspases inactivate (through cleavage)?
protein kinases, lamins, intermediate filaments & actin, DNA repair enzymes
In a DNA ladder apoptosis assay, a DNA ladder of ______ bp steps is observed.
What are some general cases in which an extrinsic, receptor-mediated apoptosis pathway could be observed?
viral infection, toxic agents
How many subunits does the TNF receptor have?
What does the TNFR1 death domain recruit?
FADD (Fas-associated death domain)
TRADD (TNFR-associated death domain)
Which caspase is the initiator caspase? How does it activate itself?
Procaspase 8 (2 subunits) proteolytically cleaves itself into initiator caspase 8 (4 subunits).
What does initiator caspase 8 cleave?
What are some situations that can induce intrinsic, mitochondria-mediated apoptosis?
excessive Ca2+, starvation from GFs, irreparable DNA damage
What family of proteins does Bax belong to?
Once translated, where does Bax integrate? What is released as a result
integrated into OMM; cytochrome c released
What is the apoptosome composed of?
7 each of: cytochrome c, pro-caspase 9, and cytoplasmic factors (e.g. Apaf-1)
What do the apoptosomes cleave?