Cell Cycle pt.4 Flashcards
Necrosis
uncontrolled cell death
Necrosis: cell membrane
swelling and rupture
Necrosis: cytoplasm
increased vacuolation, organelle degeneration, and mitochondrial swelling
Necrosis: nucleus
clumping and random degradation of nuclear chromatin and DNA (karyolysis)
Necrosis: cells involved
all cell types
Necrosis: inflammation
yes
Necrosis: features
failure of normal phys. pathways like homeostasis, ion transport, ATP depletion, ph balance
Necorsis: MOA
RIP1 and PARP-1 involved
stress/ca overload stimulates mitochondrial uncoupling as well as RIP3/RIP1 complex
this makes NADPH oxidase/increased O2 consumption
ROS are made as a result
ATP depletes and necrosis ensues
no caspases involved
Apoptosis
programed cell death
apoptosis: cell membrane
blebs and fragments into membrane bound apoptotic bodies
apoptosis: cytoplasm
fragmentation and shrinkage
apoptosis: nucleus
chromatin condensation and degradation by DNA cleavage leading to nuclear fragmentation
apoptosis: cells involved
hematopoietic cells and related (liquid tumors)
plays a role in solid tumors, which is most of cancers
apoptosis: inflammation
no
apoptosis: features
membrane loses asymmetry and PS is displayed
caspase/mitochondria dependent
apoptosis: MOA
fas ligand binds to receptor on surface
DISC is made with caspase 8
caspase 8 acts on caspase 3 to cause cell death
caspase 8 can also act on bid bid makes tbid tbid makes Bak Bak and Bax go to mito and cytochrome C makes apoptosome with capsase 9 and activates caspase 3 to cause cell death
BH3 proteins actovate bax
Bcl2, Bclxl inhibit bak
DNA damage stimulates ATM which goes to nucleus and stimulates p53 which stimulates BH3 proteins
apoptosis: triggers
DNA damage (membrane): trigger ATM, p53 Death receptor signaling (membrane): caspase 8 mediated cell membrane (membrane): sphingomyleniase turns it toc ceramide Mitochondrial damage (mitochondria): ceramide mediated
apoptosis: sensors
ATM
receptor
mitochondria
apoptosis: mediators
p53 BCL2 (antiapoptotic) BH3 and Bax(pro apoptotic) cytochrome C apoptotic protease activating factor 1
apoptosis: effectors
caspases
initiators: caspases 8, 9, 10
executioner: 3, 6, 7
apoptosis: pro/anti apoptotic mechanisms
Bax and Bak induce permeability by forming pores upon oligomerization
pro-apoptotic BH3 (bid, bim, bad, noxa, puma) activate bax /bak by binding anti-apoptotic Bcl2 proteins OR BH3 proteins can directly bind and activate bax/bak
Autophagy
self eating/recycling
degrades long lived cells
mostly survival response to several stresses
autophagy: cell membrane
membrane blebbing
autophagy: cytoplasm
accumulation of 2 membrane autophagic vacuoles
autophagy: nucleus
partial chromatin condensation
no nuclear and DNA fragmentation
autophagy: cells involved
all cell types
autophagy: inflammation
no
autophagy: features
no caspases, increases lysosomal activity
autophagy: MOA
complex
uses autophagy related genes (proteins) (ATG)
coiled-coil myosin-like BCL2-interacting protein (beclin-1) (Atg6)-initiation of the formation of the autophagosome (nucleation)
microtibile associated protein 1A/1B-light chain 3 (LC2) conjugation and elongation
More autophagy MOA
release of belcin from bcl2 forms class III PI3K that contributes to formation of nucleation complex
two conjugation cascades, LC3-II and Atg5-12 cascades serve to elongate nucleation complex to generate the limiting membrane
sole transmembrane Atg9 delivers addtiional membranes for limtiing membrane formation
the limiting membrane sequesters cytosolic cargo and seals itslef to form an autosome
fusion to lyosomes results in cargo degradation and nutrient release into cytosol
mitotic catastrophe
cell death that is caused by aberrant mitosis
associated with deficiencies in cell cycle checkpoint
mitotic catastrophe: membrane
no change
mitotic catastrophe: cytoplasm
larger cytoplasm with the formation of giant cell
mitotic catastrophe: nucleus
micronucleation and multinucleation, nuclear fragmentation, premature chromosome condensation, formation of nuclear envelopes around clusters of missegregated chromosomes
mitotic catastrophe: cells involved
most dividing cells
mitotic catastrophe: inflammation
no
mitotic catastrophe: features
no caspase in the early stage, abnormal CDK1/cyclin B activation
mechanisms for the induction of the mitotic catastrophe
- defects in cell cycle checkpoints
- hyperamplification of centrosomes
3, caspase-2 activation during metaphase
defects in cell cycle chekpoints that trigger mitotic catastrophe
p53-G2 checkpoint
PUB-related kinase (BUBR) spindle checkpoint
increased expression of APC genes-spindle assembly
hyperamplification of centrosomes that trigger mitotic catastrophe
usually in subsequent cell cycle CDK2/cyclin E/A (S phase)
caspase-2 activation during metaphase that trigger mitotic catastrophe
delayed apoptosis
DNA damage at G2/M interferes with
p53
fate of cells with abberant mitosis
die without exiting mitosis-mitotic death
proceed to G1 and continue division for amny cycles and then die-delayed cell death
exit mitosis and undergo permanent G1 arrest-senescence
Senescence
permanent cell cycle arrest, reproductive death
can be a replicative senescence related to telomere shortening
antitransformation mechanism due to cellular damage
senescence: cell membrane
no change
senescence: cytoplasm
flattening and increased granularity
senescence: nucleus
distinct heterochromatic structure
senescence: cells involved
all types of cells
senescence: inflammation
yes but induced by secretory factors from the senscent cell
two pathways of senescence pathway
p53-p21
p16-Rb