apoptosis Flashcards

1
Q

reasons for apoptosis

A

harmful cells eg during DNA damage developmentally defective cells eg self reactive lymphocytes excess cells eg during liver regeneration/embryonic development obsolete cells eg (breast cells once lactation not needed) exploitation (chemotherapy)

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2
Q

necrosis vs apoptosis

A

unregulated cell death- inflammation associated, cell disruption regulated cell death- no cell disruption, no inflammation

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3
Q

what occurs in necrosis

A

membrane becomes permeable, cell SWELLS and ruptures (basically explodes), and proteases are released= digestion of cells local inflammation occurs

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4
Q

what occurs in apoptosis

A

two phases- latent phase where death pathways activated, but cell looks the same execution phase- loss of microvilli, cells SHRINKS (rather than swells, chromatin condenses, and membrane-enclosed bits bud off (membrane remains so NO inflammation) and are removed by macrophages

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5
Q

DNA fragmentation

A

occurs in apoptosis- cell becomes like blobs

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6
Q

other types of cell death

A

apoptosis-like PCD (programmed cell death)- some features of apoptosis necrosis-like PCD- some features of apoptosis before cell lysis thus there’s a GRADED responses

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7
Q

mechanisms in apoptosis

A

executioners- caspases starting death programme (death receptors+mitochondria) Bcl-2 family stopping death programme

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8
Q

caspases

A

they are proteases than cause proteolysis by cleaving cysteine and aspartate (C and AS= start of word caspase)

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9
Q

initiator and effector caspases- domains

A

they both have P10 and P20 domains, but initiator caspases have CARD and DED domains, which are cleaved later on

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10
Q

caspase maturation

A

they are produced as procaspases, which have prodomains eg DED- these are then cleaved

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11
Q

caspase cascade

A

like kinase cascade, except CLEAVAGE occurs rather than phosphorylation caspase 8/9 (intiator) cleave and activate caspase 3 and 7 (effector), which carry out apoptosis

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12
Q

what effector caspases do

A

cleave/inactivate proteins or complexes eg nuclear laminins also activate other enzymes by cleavage of inhibitor molecules eg nucleases

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13
Q

how caspase cascade activated

A

extrinsically (by receptors) or intrinsically (through mitochondria)

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14
Q

DIAGRAM death receptors including domains, procaspase recruited and complex formed

A

a ligand forms a TRIMERIC receptor (not dimeric like before) with cysteine rich domains, and intracellularly there are death domains (DD) FADD is recruited, and procaspase 8 is recruited to form a DISC COMPLEX- procaspase then activated

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15
Q

adapter proteins in receptor pathway and domains

A

pathway uses adaptor proteins as well, either FADD (activatory- has DD and DED domain), or FLIP (inhibitory, has only DED domains)

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16
Q

apoptosis via mitochondrial regulation

A

cell stress/DNA damage through P53 causes loss of mitochondrial membrane potential= cytochrome C release= APOPTOSOME COMPLEX (APAF-1 with caspase 9 and cyt C) forms

17
Q

DIAGRAM apoptosome and difference between necrosis and apoptosis

A

known as wheel of death- ring in middle, which has cytochrome C on outside formation of apoptosome requires ATP UNLIKE NECROSIS

18
Q

DIAGRAMS link between receptor and mitochondrial death pathways

A

caspase 8 cleaves bid, which enhances intrinsic pathway by causing more release of mitochondrial proteins

19
Q

what modulates apoptosis and proteins

A

BCL-2 family proteins, 3 groups which all have BH3 (group 3 has BH3 only)

20
Q

BCL 2 family proteins- anti-apoptotic and pro-apoptotic with difference between

A

anti- BCL-2 and BCL-xL- anti are MITOCHONDRIAL pro- Bid, bad, bax and bak: pro move between cytosol and mitochondria

21
Q

pathway in regulation of cell cycle/apoptosis

A

same receptor that activates RAS/ERK pathway activates PI3-K, which activates PDK-1, which activates PKB/AKT, causing survival

22
Q

PI3K vs PKB/AKT

A

PI3K is a LIPID kinase, PKB/Akt is a PROTEIN kinase

23
Q

what PKB/Akt does

A

phosphorylates and thus inactivates Bad AND caspase 9 inactivates FOXOS (they activate apoptosis-promoting genes) cause protein synthesis

24
Q

what opposes PI3K

A

PTEN, a lipid phosphatase, thus it’s pro-apoptosis

25
Q

other things that inhibit apoptosis apart from PI3K

A

IAPs, which bind to caspases to inhibit EXTRINSIC pathway

26
Q

summary of anti-apoptotic pathways

A

inhibition of intrinsic pathway- Bcl-2/Bcl-xL extrinsic- FLIP+IAPS PI3K growth factor pathway