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30 cell biology > L17 - Apoptosis, necrosis and exitotoxicity > Flashcards

L17 - Apoptosis, necrosis and exitotoxicity Flashcards

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1
Q

define apoptosis

A

programmed cell death

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2
Q

define necrosis

A

cell death from acute injury

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3
Q

define excitotoxicity

A

type of cell death in neuronal tissue

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4
Q

list some causes of necrosis

A
  1. ischaemia
  2. injury
  3. hypoxia
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5
Q

list some causes of apoptosis

A
  1. withdrawal of GF
  2. chemo
  3. contact with cytotoxic T cells
  4. development
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6
Q

what are some characteristics of necrosis

A
  1. membrane damage

2. leakage of cellular contents

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7
Q

what does leakage of cellular contents in necrosis lead to?

A

inflammatory response

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8
Q

what are some characteristics of apoptosis

A
  1. intact membrane with blebbing
  2. no leakage of cellular contents
  3. condensed chromatin
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9
Q

define blebbing

A

when the cytosol separates from the membrane leading to circular protrusions

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10
Q

why is preventing cell leakage during apoptosis important?

A
  1. avoid triggering inflammatory response

2. in neurons, release of exocytotic mediators eg glutamate from a cell can cause damage to nearby neurons

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11
Q

describe process of apoptosis

A
  1. chromatin condensation
  2. blebbing
  3. cell fragmentation forming apoptotic bodies
  4. apoptotic bodies engulfed by phagocytes
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12
Q

list some reasons why cells undergo apoptosis

A
  1. metamorphosis (tadpole tail)
  2. served developmental purpose (eg fetus hand development from bud - fingers)
  3. cells infected by virus
  4. cancer cells
  5. cells with excessively damaged DNA
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13
Q

what assay can detect apoptotic cells

A

TUNEL assay

  1. run gel electrophoresis of cells induced apoptosis
  2. overtime the ladder will increase as more fragments are forming
  3. this generates more free ends of DNA
  4. TUNEL assay uses fluorescence to detect these free ends
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14
Q

what membrane lipid can act as a signalling molecule during apoptosis and how

A

phosphatidylserine

flips and concentrates on outer layer which signals to phagocytes

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15
Q

what enzymes drive apoptosis

A

caspases (class of protease)

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16
Q

characteristics of caspases

A

proteases that contain cysteine in active site

17
Q

caspases cleave their substrate at what site?

A

aspartate sites

18
Q

what is CAD

A

Caspase dependant DNAase

19
Q

what is the role of ICAD

A

binds to CAD enzymes inhibiting apoptosis

20
Q

how do caspases trigger apoptosis?

A
  1. cleave ICAD-CAD rendering DNAase active
  2. cleave lamins leading to nuclear envelope breakdown and fragmentation
  3. cleave gelsolin causing blebbing
21
Q

what are the two apoptotic pathways

A

intrinsic (responding to intrinsic signals)

extrinsic (responding to extrinsic pathways)

22
Q

give examples of intrinsic signals

A

cytotoxic drugs

DNA damage

23
Q

describe the extrinsic apoptosis pathway

A
  1. transmembrane death receptors (part of tumour necrosis factor - TNF- receptor family) respond to extrinsic signals by activating caspases
24
Q

describe thee intrinsic apoptosis pathway

A
  1. stimuli cause leakage of mitochondrial membranes
  2. cytochrome C leaks from M into cytoplasm
  3. cytochrome C activates caspases
25
Q

what activates caspases

A

cytochrome C

transmembrane death receptors

26
Q

what amino acid can lead to excitotoxicity in nerve cells

A

glutamate

27
Q

what can cause glutamate release

A

hypoxia / hypoglycaemia

28
Q

explain the process of neuronal cell death by excitotoxicity

A
  1. hypoxia/hypoglycaemia can cause glutamate leakage from broken vesicles
  2. leads to prolonged activation of receptors (AMPA&NDMA)
  3. AMPA causes NA+ influx which depolarises membrane
  4. this dislodges Mg2+ from NMDA receptor leading to Ca2+ influx
  5. Ca2+ dependant enzymes activated (lipases, DNAases)
29
Q

why does excitotoxicity only occur in nerve cells

A

only nerve cells express surface glutamate receptors

30
Q

what enzymes are activated during excitotoxicity

A

Ca2+ dependant ones (lipases, DNAases)

31
Q

what receptors does glutamate bind to in nerve cells

A

AMPA

NMDA

32
Q

what medical conditions can lead to severe apoptosis

A

heart attack

stroke

33
Q

name a disease caused by excessive apoptosis

A

diabetes type 1

34
Q

insufficient apoptosis can lead to what disease?

A

autoimmune diseases

35
Q

how are the effects of glutamate reduced (excitotoxicity)

A

glial cells take up glutamate from the synaptic cleft and convert it to glutamine

36
Q

in what diseases can excitotoxicity occur?

A
  1. stroke
  2. epilepsy
  3. Parkinson’s
  4. Alzheimer’s
37
Q

give an example of how apoptosis can be detected

A

by binding of labelled annexin V.

38
Q

what organisms never undergo apoptosis?

A

bacteria

30 cell biology (21 decks)

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