SFP: apoptosis and necrosis

Question 1

what are the three modes of cell death

Answer 1

apoptosis: programmed cell death
autophagy: organelle recycling or self eating
necrosis: progressive cell injury

Question 2

what stimulates autophagy

Answer 2

nutrient depravation

Question 3

describe the major elements of apoptosis

Answer 3

• shrinkage
• chromatin compaction
• breakup of nuclear envelope
• nuclear fragmentation
  -forming of apoptotic bodies that are then taken up by phagocytosis

Question 4

describe apoptotic bodies: what they are and how they’re recognized

Answer 4

membrane enclosed fragments of cells; they are recognized by phagocytes due to phosphotidyl serine being on the outside instead of the inside of the membrane

Question 5

when DNA fragmentation is visualized in gen electropheresis, what does it look like?

Answer 5

laddering

Question 6

what are the two pathways for apoptosis

Answer 6

1. extrinsic: signal from a death ligand/receptor
2. intrinsic: directly related to mitochondrial dysfunction

Question 7

briefly describe the extrinsic apoptotic pathway

Answer 7

• TNF or FAS binds to its receptor
• adaptor proteins are created
  -initiator caspases cleave executioner caspases
  -executioner caspases degrade intracellular components

Question 8

what is a common mechanism between extrinsic and intrinsic methods

Answer 8

caspases; initiator caspases cleave procaspases into executioner caspases

Question 9

what is different about the structure of initiator caspases

Answer 9

they have a longer N terminal with CARD or DED domains that are required for activation of procaspases

Question 10

describe the structure of activated caspases

Answer 10

they are formed into tetramers composed of two small and two large subunits. the prodomain has been cleaved.

Question 11

briefly describe the intrinsic pathway

Answer 11

• there is a disruption to mitochondrial integrity
• increased ROS and oxidative stress and VDAC pore opening
• increased calcium concentration
• cytochrome C release from mitochondria
• cytochrome C drive apoptosis via capsases

Question 12

name the steps in a formation of an apoptosome

Answer 12

1. cytochrome C release
2. cytochrome C binding to apaf1
3. apoptosome formed

Question 13

what is an apoptosome

Answer 13

it acts like an initiator capsase in the intrinsic pathway; it cleaves initiator capsases

Question 14

what are Bcl2 proteins

Answer 14

they’re proteins on the mitochondria that determine whether the cell will go into apoptosis

Question 15

what are the pro-apoptotic Bcl2 family proteins? anti-apoptotic?

Answer 15

pro: BAD, bax
anti: bcl2, bcl-xl

BID binds to one of these and depending on what it binds to, cytochrome C will be repressed or released

Question 16

release of too much calcium can activate ___. what will this do?

Answer 16

calpain; lead to activation of caspases

Question 17

what are some diseases associated with increased apoptosis

Answer 17

AIDS, neurodegeneration, toxin-induced liver disease

Question 18

what are some diseses associated with decreased apoptosis

Answer 18

cancer, viral infection

Question 19

what are the stages of autophagy

Answer 19

1. isolation membranes (autophagic vacuoles) are made from the ER
2. they surround damaged organelles and form autophagosomes
3. lysosomes fuse with autophagosomes
4. lysosomal degradation allows the cell components to be recycled and reused.

Question 20

describe the role of in beclin, ATG, and LC3 in autophagy

Answer 20

beclin and ATG : involved in forming phagophore and elongation of the membrane; can be blocked by Bcl2
LC3: allows for formation of autophagosome

Question 21

how does insulin regulate autophagy

Answer 21

a lot of insulin will lead to PKB which acitvates mTOR which prevents autophagy

Question 22

what happens if an animal born is deficient is autophagy

Answer 22

they die in the first 24 hours

Question 23

describe necrosis

Answer 23

cell death due to unexpected cell damage; the process is highly inflammatory

Question 24

name the steps of necrosis

Answer 24

1. increased intracellular calcium
2. calcium activates lytic enzymes that degrade molecules in membranes
3. intracellular material spills out of the cell
4. intracellular components promote inflammation

Question 25

what are DAMPS and PAMPS

Answer 25

DAMPS: damage associated molecular patters; intracellular proteins being released from damaged cells

PAMPS: pathogen associated molecular patterns; LPS, cell wall components, flagellin

lead to formation of inflammasome

Question 26

describe forming of inflammasomes to deal with inflammation

Answer 26

1. activate pattern recognition receptors (TLR) via PAMPS or DAMPS that result in forming a scaffold of proteins
2. upregulation of inflammatory mediators (IL1 IL18)
3. activation of caspase 1
4. caspase 1 processes IL18 and mount the inflammatory response