L15: Apoptosis, Necrosis & Excitotoxicity

Question 1

3 types of cell deaths

Answer 1

1) Necrosis
2) Apoptosis
3) Excitotoxicity

Question 2

Define Necrosis

Answer 2

Traumatic cell death from acute injury (traumatic hit)

Question 3

Define Apoptosis

Answer 3

Programmed cell death

Question 4

Define Excitotoxicity

Answer 4

Specialised cell death of 1 type of tissue occuring in neural tissue

Question 5

2 main reasons why cells commit apoptosis

Answer 5

1) During metamorphosis
2) Elimination of cells that have served their purpose during development

Question 6

3 biochemical characteristics of apoptosis

Answer 6

1) DNA split by endonuclease
2) Phosphatidylserine is located inside the bilayer and releases a ‘eat me’ signal
3) Apoptotic cells lose electrochemical potential and changes membrane potential

Question 7

Role of caspases

Answer 7

Enzymes that drive apoptosis in multicellular eukaryotes

Question 8

2 examples of caspase targets

Answer 8

1. ICAD
2. Structural proteins (lamins & gelsolin)

Question 9

What does caspase cause?

Answer 9

Rapid Cell Death

Question 10

Why are caspases called caspases?

Answer 10

Proteases with Cystein at active sites and cleave their substrate at specific ASPartic sites

Question 11

2 apoptotic pathways

Answer 11

1) Extrinsic (Death receptor pathway)
2) Intrinsic (Mitochondrial pathway)

Question 12

Features of extrinsic pathway

Answer 12

1) Responds to extracellular signals to indicate if a specific cell no longer needed for organism

2) Involves transmembrane death receptors which are members of the tumor necrosis factor (TNF) receptor family

Question 13

Features of the intrinsic pathway

Answer 13

1) Apoptotic stimuli causes mitochondrial membranes to become leaky, to release cytochrome C into cytoplasm which activates caspase

Question 14

What is intrinsic pathway responsive to ?

Answer 14

1) Cytotoxic drugs that enter the cell
2) DNA damage

Question 15

Describe UV-C (180-290nm)

Answer 15

Not found in daylight as it is absorbed by ozone layer- used as sterilisation agent

Question 16

Describe UV-B (290-320nm)

Answer 16

Major mutagenic fraction of sunlight

Question 17

How does UV damage DNA?

Answer 17

• UV hits adjacent thymines, forces them to make covalent bonds, and attach
• When DNA polymerase replicates, it inserts a wrong base causing a mutation

Question 18

What can cause a form of cell death specific to neural tissue (excitotoxicity)?

Answer 18

Disturbance in glutamate homeostasis

Question 19

2 ways glutamate is synthesised

Answer 19

1) From a precursor in the Krebs Cycle, then taken up by exocytic vesicles

2) Involves what happens after it has been used as a neurotransmitter

Question 20

2nd step

What does the process involving glutamate after it has been used as a neurotransmitter involve?

Answer 20

Nerve terminals & glial cells reuptake released glutamate, via membrane transporters

Question 21

3rd step

What happens after glutamate is reuptook via membrane transporters?

Answer 21

In the glia, glutamate is converted to glutamine

Question 22

4th step

What happens after glutamate is converted to glutamine?

Answer 22

Glutamine is transported from glia into neuronal terminal via transporters in glial & neuronal terminal membranes

Question 23

5th step

What happens after glutamine is transported?

Answer 23

In neuronal terminal, glutamine is converted to glutamate

Question 24

6th step

What happens after glutamine is converted to glutamate?

Answer 24

Glutamate is taken up into vesicles & stored, then released by exocytosis

Question 25

Why is prolonged activation of receptors dangerous?

Answer 25

1) Glutamate binds to NMDA & AMPA
2) Activated AMPA receptors allow NA+ to enter the cell
3) This dislodges Mg2+ from NMDA receptor, allowing entry of Ca2+

Prolonged exposure to glutamate leads to prolonged entry of Ca2+