14 - Cell Death Flashcards
What are the 2 types of cell death?
apoptosis | necrosis
What is apoptosis?
a signal is what causes cell death | everything condenses = cell blebbing = apoptotic bodies
What is necrosis?
injury causes cell death (ie: lack of O2) | lose integrity of cell = membrane stops working = water rushes in = cell lysis
What is the difference between apoptosis and necrosis?
apoptosis = cell membrane remains intact | necrosis = membrane is broken
How can necrosis lead to inflammation?
cell lysis = genetic material escapes = immune system sees that and induces inflammation
How are the apoptotic bodies removed?
macrophages phagocytose them
What are the 2 pathways to induce apoptosis?
intrinsic and extrinsic
What is the intrinsic pathway of apoptosis?
mitochondrial pathway
What are the 2 sides to the Bcl-2 family? Who is the main player of each family and who has the bigger family?
pro-survival side = Bcl-2 | pro-apoptotic side = Cax (bigger family)
What is the function of the pro-apoptotic proteins?
pro-apoptotic proteins inhibit Bcl-2-like proteins and its activities | form an octamer complex on mitochondrial membrane
What is displacement in the mitochondrial pathway (intrinsic)?
originally Bax is sequestered by Bcl-2 | Bim displaces Bax = Bcl-2+Bim so Bax can oligomerize = octamer complex on mitochondrial membrane
What is an octamer complex?
pore on mitochondrial membrane = stuff inside leaks out into cytoplasm
What is the main reason why octamer complex happens on the mitochondrial reason? Why do you want stuff from mitochondria to leak out?
release cytochrome c into cytoplasm
What is the role of cytochrome c in the intrinsic apoptosis pathway?
to complete the apoptosome formation
What are the 3 proteins that form the apoptosome?
cytochrome c | Apaf-1 | procaspase-9
What is the main function of the apoptosome?
to cleave procaspase-9 into caspase-9 = initiates caspase cascade
What are caspases?
proteases | inactive unless prodomain is cleaved into smaller subunits which associate = active caspase
What is the executioner caspase?
caspase 3
What is the role of caspase 3?
to proteolytically cleave the other inactive caspase = speeds up apoptosis
Until when can apoptosis be paused and reversed? What is the point of no return?
until the DNA is chopped up
In apoptosis, what chops up the DNA and what is the nature of this molecule?
CAD = DNase
What inhibits CAD?
ICAD
How is CAD activated?
caspase 3 cuts ICAD from CAD = activates CAD
What is PARP?
a detector of DNA damage like ATM and ATR = tells p53 of the damage
In the DNA degradation step of apoptosis, what prevents PARP from telling p53 to fix the DNA degradation happening?
caspase 3 cleaves PARP = inactive PARP = no DNA repair
What is another term for the extrinsic apoptosis pathway?
receptor-mediated apoptosis
What are the 2 ways that extrinsic apoptosis pathway can be carried out?
death receptors | perforin/granzymes
Which cells are responsible for the extrinsic apoptosis pathway?
CTLs and killer cells (NK cells)
How is the extrinsic apoptosis pathway carried out using perforin/granzymes?
CTLs expel perforin = forms pore on target cell membrane | CTLs throw in granzymes that will cleave caspase pro-domains
There are many death receptors and all cells have them. What is one that is commonly used and discussed?
Fas/Fas ligand
How is the extrinsic apoptosis pathway carried out using the death receptors?
target cell has Fas receptor | CTL/NK cell has Fas ligand | 3 FasR/FasL = forms complex with procaspases = get cleaved = apoptosis
When do cells know they have to die?
their telomeres getting short
How can cells escape cell death? What are 2 genes should they turn on?
telomerase | Bcl-2
What are 2 cells that you don’t want to die?
stem cells | neurons
What are IAPs?
inhibitors of apoptosis proteins
What is the function of IAPs?
to bind to active caspases so they can’t cleave all of their targets
Do tumor cells use IAPs?
Yes, they up-regulate IAP expression so they don’t die
How would you target the DNA of the tumor cell?
UV light | drugs that target the DNA
What is the key to keeping macrophages away?
CD31 adhesion receptor interaction
What does the tumor need to do with CD31 in order to not get phagocytosed by macrophages?
needs to express CD31 so it repels and detaches macrophages
