L12 resisting cell death Flashcards
definition of apoptosis, necrosis and autophagy
apoptosis- programmed cell death
necrosis- accidental cell death
autophagy- recycling of cellular components
is apoptosis passive or active?
active
what are the human homologues of ced 3,4,9
ced 3= caspase-9
ced 4= apaf-1
ced9= bcl2
what are the stages of apoptosis?
condensaton of nuclei, fragmentation of DNA
condensation and fragmentation of cytoplasm
formation of apoptotic bodies
phagocytic clearance
explain stage 2 of apoptosis: cell shrinkage and chromatin condensation
cytoplasm shrinks following cleavage of actins and lamins
organelles tightly packed
chromatin condenses following chromatin and nuclear structural protein breakdown
nuclei= horse shoe appearance
what genes need to be switched off for apoptotic pathways to begin?
normally apoptosis is repressed
so need to repress the repressors
bcl2 repression/ switch off= activation of cytochrome c and apaf-1= activation of caspase 9= apoptosis
how do caspases become activated and once activated how do they activate others? what is this process known as?
cleavage of their n-terminal polypeptide sequence= activation
proteolytic cascade= one caspase activates another to amplify response
what are the initiator caspases and which are the executioner/ effector caspases?
initiator= 8, 9, 10, 12
effector= 2, 3, 6, 7
function of FLIP protein?
turn off activation at different stages of extrinsic pathway to control apoptosis
what protein is necessary for intrinsic and extrnsic pathway cross talk?
BID protein
caspase 8 in extrinsic pathway causes cleavage of BID
punch holes in mitochondria membrane= activation of intrinsic pathway
in the granzyme pathway, granzyme b enters the cell what is its functions once in the cell?
activates caspases to degrade proteins
bind icad and prevent icad inhibition on cad= cad degrades dna
granzyme cleaves BID= intrinsic pathway
why might the cell undergo necrosis instead of apoptisis?
decrease in availability of caspases or intracellular atp
metabolic stresses- change in ph, hypoxia
what are some morphological differences between apoptosis and necrosis?
apoptosis- individual cells. necrosis- groups
apoptosis- decreased cell volume. necrosis increased
apoptosis- condensed chromatin. necrosis fragmented
how does mtorc work in autophagy?
nutrient rich= mtorc active= inhibits atg14 proteins by phos
nutrient poor- mtorc inhibited= atg protiens form phagophore
phagophore- double membranebound vesicle engulfs components to form autophagosome
what are some alternative methods to induce apoptisis without targeting p53?
stimulate death receptors
downregulate bcl2
introduce wiltype bcl2
genome editing with CRISPR
