Exam 3 Apoptosis And Necrosis

Front 1

What is this?

-cell murder
-due to unexpected or accidental cell damage
-overwhelming insults by toxins, radiation, heat, trauma, lack of oxygen

Back 1

Necrosis

Front 2

what is this?

-non-traumatic cell death, “programmed cell death”, “cell suicide”
-may result from viral infections, cellular stress, DNA damage (prevention of cancer), or as part of normal development and maintenance of tissue

Back 2

Apoptosis

Front 3

is this apoptosis or necrosis?

Physiological or pathological
Single cells
Energy dependent
Cell shrinkage
Membrane integrity maintained
Role for mitochondria and cytochrome C
No leak of lysosomal enzymes
Characteristic nuclear changes
Apoptotic bodies form
DNA cleavage
Activation of specific proteases
Regulated process
Evolutionarily conserved
Dead cells ingested by neighbouring cells

Back 3

apoptosis

Front 4

Is this apoptosis or necrosis?

Always pathological
Sheets of cells
Energy independent
Cell swelling
Membrane integrity lost
No role for mitochondria
Leak of lysosomal enzymes
Nuclei lost
Do not form
No DNA cleavage
No activation
Not regulated
Not conserved
Dead cells ingested by neutrophils and macrophages

Back 4

necrosis

Front 5

The necrosis pathway:

-dependent on loss of membrane homeostasis, especially ...
-... influx into cytosol (from intracellular stores and from ECM) --> ... is allosteric activator of many degradative enzymes

-... --> cytosolic protease
-... --> lysosomal protease

Back 5

Ca2+ homeostasis
Ca2+
Ca2+

calpain
cathepsin

Front 6

Necrosis:

cell ..., ... form in membrane, intracellular contents leak out into surrounding tissue, eventual cell ...

Back 6

swells
holes
lysis

Front 7

necrosis:

major ... results

-cell contents leak into ECM, damaging surrounding tissue
-production of ... from Arachadonic Acid produced during lipolysis of membrane phospholipids
-recruitment of inflammatory mediators (... and ...) - cleans up cell debris

Back 7

inflammation

eicosanoids
macrophages and neutrophils

Front 8

Apoptosis is a natural normal process that’s found throughout ... and even through adulthood.
-Impt for processes like the development of the fingers
-... hands will develop if apoptosis fails here

Back 8

embryogenesis
webbed

Front 9

the apoptotic pathway:

non-traumatic, highly ordered process

3 phases involved:
-... (external or internal signals)-when a signal is received by the cell that something is wrong
-... (pro-apoptotic signals balanced against anti-apoptotic cell survival signals)
-... (carried out by proteolytic enzymes called caspases, which digest the cell)

Back 9

Initiation phase
Signal integration phase
Execution phase

Front 10

which 4 players must be present for apoptosis to occur?

-...
-... (releases cytochrome C)
-... (protein)
-... (protease that dismantles the cell)

Back 10

death receptor
mitochondrion
bcl-2 protein
active initiator caspases

Front 11

caspases:

-Cysteine aspartate specific proteases

-present in cell as ... (zymogen precursor that must be activated by proteolytic cleavage)

-inactivate cellular ... pathways and specifically activate factors that promote ...

Back 11

procaspases
survival
cell death

Front 12

classes of caspases:

1) Initiator (activator) caspases:
-generally cleave and activate ...
-activate other enzymes
2)Effector (executioner) caspases:
-requires formation of ...
-cleave cellular proteins involved in maintaining ...
-the ones that actually dismantle the cell

Back 12

procaspases

apoptosome
cellular integrity

Front 13

Death receptor pathway:

-subset of ... receptors
-receptor forms a ... that binds TNF-1 or another death ligand (Fas ligand, p53, BAX) on its external domain
-(BAX initiates process of apoptosis)
-intracellular domain attached to cytosolic ...
-activates ... caspases, which in turn activates ... caspases, which leads to the destruction of the cell

Back 13

TNF-1 (tumor necrosis factor)
trimer
adaptor proteins
initiator
execution

Front 14

mitochondrial integrity pathway (not directly linked to receptor itself):

-intracellular signals indicate death should occur (growth factor withdrawal, cell injury, release of certain steroids, inability to maintain low intracellular Ca2+)
-pathway begins with release of ... from mitochondria (1st step)
-... (one of the markers of apoptosis) binds ...(only found during cell death) and forms the ..., which in turn activates execution caspases

Back 14

cytochrome c
cytochrome c
Apaf
apoptosome

Front 15

-formation of the apoptosome by ... and ...

-apoptosome specifically activates the ...

Back 15

cytochrome c
Apaf-1

execution caspase

Front 16

the ... family are the decision making signals

Back 16

Bcl-2

Front 17

Put these into the right categories:

Categories:
-protectors (anti-apoptotic): protect cell from undergoing apoptosis
-killers (pro-apoptotic): trying to promote cell death
-regulators: go either way. Responds to both signals

1)Bax, Bak, Bok/Mtd
2)Bcl-2, Bcl-xL, Bcl-W
3)Bad, Bid, Bim

Back 17

-Protectors: Bcl-2, Bcl-xL, Bcl-W

-Killers: Bax, Bak, Bok/Mtd

-Regulators: Bad, Bid, Bim

Front 18

Anti-apoptotic Bcl-2 members (Bcl-2, Bcl-x, Bcl-w):

-can insert into outer mitochondrial membrane to ... channel-forming pro-apoptotic factors (decreases cytochrome c release)

-may prevent assembly of apoptosome complex by binding to and inactivating cytoplasmic ...

Back 18

antagonize

Apaf-1

Front 19

Pro-Apoptotic Bcl-2 members:

some may form ..., promoting cytochrome c release (Bax, Bak, Bok)

some members called ... (regulator Bcl-2 proteins Bad, Bid, Bim) bind directly to other Bcl-2 members, either activating or inactivating them

Back 19

ion channels

BH3-only proteins

Front 20

DNA changes in apoptotic cells:

1)... aggregation (forms a ring around nucleus)
2)... condensation
3)... fragmentation (not random. organized)

-ordered DNA intranucleosomal cleavage producing a characteristic ... pattern on an agarose gel (highly specific and diagnostic of apoptosis)

Back 20

chromatin
nuclear
nuclear

“laddering”

Front 21

Membrane changes in apoptotic cells:

-cell shrinking
-membrane ... (protective mechanism so its enzymes don't spill out. prevents inflammation)
-apoptotic bodies
-membrane asymmetry
-phosphatidylserine (PS) flips from ... to ... membrane = signal to other cells saying "i'm going through apoptosis!!!

Back 21

blebbing
inner
outer

Front 22

when ... is exposed on the outer leaflet of the membrane, it's a signal to the other cells that that cell is undergoing apoptosis

Back 22

phosphatidylserine

Front 23

Inflammation isn't assoicated with apoptosis because:

-no ... of lysosomal enzymes or cellular contents into surrounding tissue

-removal of apoptotic bodies does not elicit an ... response from macrophages/neutrophils

-... affected, not ... of cells

Back 23

leakage
inflammatory
individual cells
large groups

Front 24

importance of apoptosis in disease:

lack of apoptosis when it should be occuring
-...
-...

apoptosis occuring when it should not
-... diseases, like Alzheimer's and Huntingtons
-myocardial infarction
-stroke

Back 24

autoimmunity
cancer

neurodegenerative