74922
Description
Mind Map by tanitia.dooley, updated more than 1 year ago
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Created by tanitia.dooley
almost 11 years ago
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Apoptosis
- Basic requirements
- Nutrients & O2, cell need to be in contact
with each other and this contact is signalling
chemically-so a mismatch/problem with
either signal or receptor will cause problems
- Nutrients & O2, cell need to be in contact
with each other and this contact is signalling
chemically-so a mismatch/problem with
either signal or receptor will cause problems
- humans loose between 50% & 75% of the cells
generated during cotrical development- through
programmed cell death=APOPTOSIS
- Essential in normal development &
maintaining tissue homeostasis
- Failure to regulate apoptosis= cancer, AIDS,
alzheimer's disease, parkinsons disease=
thought to be a result of deregulation of apoptosis
- 2 ways in which a cell can die: 1.
apoptosis 2. Killed by injurious agents
- Essential in normal development &
maintaining tissue homeostasis
- TNF- released from macrophages & initiate apoptosis.
- Fas= TNF family= when binds to its receptor it activates apoptosis
- Fas= TNF family= when binds to its receptor it activates apoptosis
- SMACs released from mitochondria when an
increase in permeability- bind to apoptotic
inhibitor proteins (BCL2) in cytosol which usually
inhibit apoptosis therefore apoptosis can occur
- Genetic considerations
- It is possible to breed mice with inactivated CPP32 (apoptotic factor that promotes cell
death)- they have extra layers of cells in the retina & cortex which are usually removed by
apoptosis as it removes non essential cells- however the mice have inactivated CPP32
therefore this doesnt happen. The mice die because the gene is neurone specific
- It is possible to breed mice with inactivated CPP32 (apoptotic factor that promotes cell
death)- they have extra layers of cells in the retina & cortex which are usually removed by
apoptosis as it removes non essential cells- however the mice have inactivated CPP32
therefore this doesnt happen. The mice die because the gene is neurone specific
- Death by injury
- Cells that are damaged eg by mechanical
damage (e.g. radiotherapy can disrupt
nucli and promote p53=activator of
apoptosis) & exposure to toxic chemicals
- Can be used to promote apoptosis when it is
failing to work- eg. chemotherapy-more than
one trigger/ multiple pathways for apoptosis
- Resulting in cell swelling (membrane damage, internal
& external) & cell leakage (membrane damage) =
inflammation of surrounding tissues (cytokines etc)
- Cells that are damaged eg by mechanical
damage (e.g. radiotherapy can disrupt
nucli and promote p53=activator of
apoptosis) & exposure to toxic chemicals
- Pathways
- Apoptosis
- Caspase activation- inhibition of mRNA translation=
condensation of cell & organelles= chromatin
condensation, DNA fragmentation=loss of
membrane asymmetry= membrane remains
impermeable (form smaller packages= cell
blabbing)= cells fall apart into apoptotic bodies-
these are targetted for safe removal (by lysosomes)
- Cytosol never exposed to extracellular fluid of healthy cells
- Caspase activation- inhibition of mRNA translation=
condensation of cell & organelles= chromatin
condensation, DNA fragmentation=loss of
membrane asymmetry= membrane remains
impermeable (form smaller packages= cell
blabbing)= cells fall apart into apoptotic bodies-
these are targetted for safe removal (by lysosomes)
- Necrosis
- Pro-inflammatory signalling &
cytokine production= swelling of
the cell and
organelles=chromatin
condensation= loss of mem
asymmetry= rapid loss of men
permeability= cell-membrane
explodes, remains stay
together= contents released=
inflammation of surrounding cells
- Pro-inflammatory signalling &
cytokine production= swelling of
the cell and
organelles=chromatin
condensation= loss of mem
asymmetry= rapid loss of men
permeability= cell-membrane
explodes, remains stay
together= contents released=
inflammation of surrounding cells
- What starts it?
- 1. Withdrawal of positive signals- growth factors for
neurons, interleukin 2 for mitosis 2. The receipt of
negative signals-oxidants, UV, X-rays, Chemotherapy.
Death activation factors (TNF, lymphotoxin & FasL)
- Signals that arise within the cell
- Internal signals
- Healthy cells outer mem of mitoch express Bcl-2 on their
surface- Bcl-2 is bound to Apaf-1. Internal damage
releases Apaf-1=cytochrome c leaks out of mitoch. Apaf-1
+ cytochrome c bind to caspase9 forming the apoptosome=
then activates caspases 3, 6 & 7 (effector caspases)
- p53 can also trigger activation of
caspases 8 & 10=causes
condensation of chromatin &
increases the permeability of
mitochondrial membrane causing
cytochrome C to leak out
- CASPASES-family of proteases cleaving aspartic acid
residues. They cleave eachother so caspase 9 activates
other caspases=cascade of activation. Digestion of
structural proteins, DNA degradation & phagocytosis.
Once activated cant be deactivated- packaged as part of
blebbing process to protect other cells
- p53 in cytosol can influence BCL2, Bax
interaction-BCL2 no longer inhibiting-Bax interferes
with mitochondrial mem & releases cytochrome c
- CASPASES-family of proteases cleaving aspartic acid
residues. They cleave eachother so caspase 9 activates
other caspases=cascade of activation. Digestion of
structural proteins, DNA degradation & phagocytosis.
Once activated cant be deactivated- packaged as part of
blebbing process to protect other cells
- Healthy cells outer mem of mitoch express Bcl-2 on their
surface- Bcl-2 is bound to Apaf-1. Internal damage
releases Apaf-1=cytochrome c leaks out of mitoch. Apaf-1
+ cytochrome c bind to caspase9 forming the apoptosome=
then activates caspases 3, 6 & 7 (effector caspases)
- External signals
- Fas & TNF receptors are
integral mem proteins.
Binding of their respective
death activation factors
signals the activation of
caspase 8 and so on
- FasL interaction with death domain on
internal face of membrane can lead to
destruction of mitoch/activation of
casphase 8- can then lead to DNA damage
& p53 release (further apoptotic signal)
- FasL interaction with death domain on
internal face of membrane can lead to
destruction of mitoch/activation of
casphase 8- can then lead to DNA damage
& p53 release (further apoptotic signal)
- Fas & TNF receptors are
integral mem proteins.
Binding of their respective
death activation factors
signals the activation of
caspase 8 and so on
- Internal signals
- Triggered by death activation factors
which bind to receptors at the cells surface
- Signals that arise within the cell
- 1. Withdrawal of positive signals- growth factors for
neurons, interleukin 2 for mitosis 2. The receipt of
negative signals-oxidants, UV, X-rays, Chemotherapy.
Death activation factors (TNF, lymphotoxin & FasL)
- Apoptosis
- Death by suicide
- cells shrink=mitchondria breaks down with the release of cytochrome
C= DNA degradation in their nuclei=break up into membrane wrapped
fragments= this exposes phospholipid phosphatidylserine
- Phospholipid phosphatidylserine is normally hidden in the plasma men- when
exposed it is bound by receptors on phagocytic cells (macrophages)= they engulf
the cell fragments= phagocytic cells secrete cytokines these inhibit inflammation
- Phospholipid phosphatidylserine is normally hidden in the plasma men- when
exposed it is bound by receptors on phagocytic cells (macrophages)= they engulf
the cell fragments= phagocytic cells secrete cytokines these inhibit inflammation
- cells shrink=mitchondria breaks down with the release of cytochrome
C= DNA degradation in their nuclei=break up into membrane wrapped
fragments= this exposes phospholipid phosphatidylserine
- Development
- Resorption of a tadpole tail during metamorphosis, formation of fingers & toes
of the fetes requires removal of the tissue between them, sloughing off the inner
lining of the uterus during menstruation, proper synapse formation in the brain
- Resorption of a tadpole tail during metamorphosis, formation of fingers & toes
of the fetes requires removal of the tissue between them, sloughing off the inner
lining of the uterus during menstruation, proper synapse formation in the brain
- Maintenance
- Viral infection- cytotoxic T cells kill virus infected cells by induction of
apoptosis, defects in apoptotic machinery is associated with autoimmune
diseases, DNA damage leads to improper embryonic development & cancer
- DNA damage=increased p53 produced (potent inducer of apoptosis)- mutated forms of the p53 genes are often
found in cancer cells-this permits the cell to live. Radiation & chemical used in cancer therapy induce apoptosis
- DNA damage=increased p53 produced (potent inducer of apoptosis)- mutated forms of the p53 genes are often
found in cancer cells-this permits the cell to live. Radiation & chemical used in cancer therapy induce apoptosis
- Viral infection- cytotoxic T cells kill virus infected cells by induction of
apoptosis, defects in apoptotic machinery is associated with autoimmune
diseases, DNA damage leads to improper embryonic development & cancer
- Regulation of apoptosis could account for low neuronal
counts in patients with Down's syndrome because
BCL2 (cell survival protein) is lower in post-mortem
Down's patients, while Bax remains normal- Down's
patients gernerally develop Alzheimer's disease
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