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Advanced Human Physiology > Apoptosis > Flashcards

Apoptosis Flashcards

1
Q

What is apoptosis?

A

Programmed cell death without causing an immune reaction

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2
Q

How are apoptosis and necrosis different?

A

Apoptotic cells don’t burst and release toxins when they die. They are phagocytosed so there are no waste products released into the tissues, meaning there is no inflammatory response induced in the host tissues.

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3
Q

Summarise the process of apoptosis.

A

Tightly regulated pathway leading to cell death
Cells about to die activate intracellular enzymes which break down nuclear DNA & cellular proteins
Plasma membrane remains intact
Apoptotic bodies targeted by phagocytes
Removed before contents leak into cytoplasm

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4
Q

Why is there no inflammatory response in apoptosis?

A

The apoptotic cell is phagocytosed before it lyses open, so the intracellular contents are not released into the surrounding tissues.

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5
Q

When DNA is fragmented, how many base pairs are the fragments made up of?

A

180bp, and multiples of 180bp (360, 540 etc…)

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6
Q

When is apoptosis important in normal processes?

A

Embryogenesis
Hormone–dependent involution
Cell deletion in a proliferating population

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7
Q

When is apoptosis seen in embryogenesis?

A

Programmed cell death (loss of webbing between toes and fingers), Metamorphosis in frogs (tadpole’s tail disappears when frog grows limbs), Organogenesis.

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8
Q

What is involution?

A

The shrinking or return of an organ to a former size

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9
Q

Give examples of apoptosis that occur during Hormone-dependent involution

A

Apoptosis of the cells that attach the uterine lining to the uterine muscle, causing menstrual flow
Regression of breast tissue when lactation ceases
Ovarian follicular atresia at the menopause

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10
Q

What is the purpose of apoptosis in a proliferating population?

A

Keeping the number of cells of the intestinal epithelia within the crypts constant

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11
Q

What external stimuli can cause cells to enter the apoptotic pathways?

A

Injurious stimuli
Viral diseases
Pathological Atrophy
Tumours

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12
Q

Give examples of injurious stimuli that can induce apoptosis

A

Radiation
Cytotoxic drugs
Anti-cancer drugs

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13
Q

Give examples of viral diseases that can induce apoptosis

A

Viral hepatitis

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14
Q

Give examples of pathological atrophy that can induce apoptosis

A

After blockage of a duct to a gland

Pancreatic cell death

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15
Q

Give an example of how tumours can display apoptosis

A

During tumour regression

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16
Q

What morphological changes to cells occur during apoptosis?

A
  1. Cell shrinkage
  2. Chromatin condensation
  3. Cytoplasmic blebs & apoptotic bodies
  4. Phagocytosis of apoptotic cells/cell bodies
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17
Q

What can be seen during cell shrinkage?

A

Smaller cells
Dense cytoplasm
Organelles tightly packed

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18
Q

What can be seen during chromatin condensation?

A

Chromatin aggregates peripherally into dense masses
Nucleus may break up into fragments
(Characteristic feature of apoptosis)

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19
Q

What can be seen in cytoplasmic blebs & apoptotic bodies?

A

Surface blebbing
Fragmentation into apoptotic bodies
Cytoplasm & organelles with/without nuclear material

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20
Q

What can be seen during phagocytosis of apoptotic cells/cell bodies?

A

Apoptotic bodies degraded within lysosomes

Allows healthy cells to replace the damaged ones

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21
Q

What are the pathways by which apoptosis can occur?

A

Extrinsic pathway

Intrinsic pathway

22
Q

How can the extrinsic pathway be activated?

A

Specific ligands that activate death receptors on the cell membrane

23
Q

How can the intrinsic pathway be activated?

A

Withdrawal of growth factors/hormones, Injury, or the action of cytotoxic T lymphocytes.

24
Q

How are the apoptotic mechanisms controlled and regulated?

A

Controlled by members of the Bcl-2 family of proteins that either inhibit or promote the cell’s death.

25
Q

What is the function of the executioner caspases?

A

Activate latent cytoplasmic endonucleases & proteases

Degrade nuclear & cytoskeletal proteins.

26
Q

What is the result of executioner caspase activation?

A

Results in a cascade of intracellular degradation, including fragmentation of nuclear chromatin & breakdown of the cytoskeleton.

27
Q

What is the end result of apoptosis?

A

The end result is formation of apoptotic bodies containing intracellular organelles and other cytosolic components

Apoptotic bodies also express new ligands for binding & uptake by phagocytic cells

28
Q

What occurs as a consequence of damage to the cell?

A

Ca2+ move into the cell and activate Calpain

29
Q

What is the function of Calpain?

A

It begins to break down the lipid bilayer of the cell, causing disruption of the cellular processes within the cytoplasm.

30
Q

In a normal cell (not undergoing apoptosis) what is the function of Bcl2?

A

Prevents Calpain from breaking down the cell membrane.

31
Q

If a cell is irradiated or chemically damaged, what happens to Bcl2?

A

The amount of Bcl2 produced is decreased.

32
Q

If the amount of Bcl2 is reduced, what happens?

A

Calpain can then begin to fragment the cell membrane.

33
Q

What is the function of Bcl2?

A

It prevents activation of Calpain and maintains the membrane potential of the mitochondria at a particular voltage.

34
Q

What happens to the mitochondria in absence of Bcl2?

A

The membrane of the mitochondria becomes unstable, causing the membrane potential to drop, and allowing cytochrome C, free radicals, and AIF to leak out into the cytoplasm

35
Q

What effect do the free radicals released from the mitochondria have on the apoptotic cell?

A

They enhance the effect of Calpain, causing further degradation of the cell membrane, causing the cell to become more permeable.

36
Q

What is AIF?

A

Apoptosis inducing factor

37
Q

What is the function of AIF?

A

Initiates the breakdown of DNA

38
Q

What happens when cytochrome C is released from the mitochondria?

A

It binds to 2 molecules of procaspase and 2 molecules of Apaf-1, forming the apoptosome.

39
Q

What is the function of the Apoptosome?

A

It activates Caspase 9, which triggers the Caspase Cascade.

40
Q

What occurs when Caspase 9 is activated?

A

It activates the Effector Caspases 3, 6, and 7, which then work to break up the DNA.

41
Q

Describe what occurs during Mitochondrial leakage.

A

Increased cytosolic Ca2+ levels induces permeability (MPT) of mitochondrial membrane.
First rate-limiting event of apoptosis.
Apoptogenic factors leak into cytoplasm from mitochondria

42
Q

Describe the effect of apoptogenic factors.

A

Cytochrome c & apoptosis inducing factor (AIF) begin cascade of proteolytic activity
Causes DNA fragmentation, DNA mutations, cell death.

43
Q

Describe the function of cytochrome C

A

A key protein in electron transport
Forms a multimeric complex with Apaf-1, a protease,
activates procaspase 9
Begins a cascade of activation of d-caspases.

44
Q

What other regulatory proteins are involved in determining whether apoptosis occurs?

A 
Smac
Diablo
Bcl-2
Bcl-X:
MPT
45
Q

What molecules can enhance the apoptotic pathway?

A

Smac

Diablo

46
Q

What is the function of Smac and Diablo?

A

Released from mitochondria
Prevents IAP (inhibitor of apoptosis) from interacting with caspase 9
Leads to apoptosis.

47
Q

What is the function of Bcl-2 and Bcl-X?

A

Prevent pore formation
Block release of cytochrome c from mitochondria
Prevent activation of caspase cascade & apoptosis

48
Q

What is MPT?

A

Mitochondrial Permeablility Transition

49
Q

What is the function of MPT?

A

MPT is involved in the mitochondrial generation of reactive oxygen species:
plays a role in the degradation phase of apoptosis
(i.e. plasma membrane alterations).

50
Q

What initiates the Extrinsic Pathway?

A

Fas ligand binds to the Fas receptor, activating the Fas Activated Death Domain (FADD). FADD activates Caspase-8.

Advanced Human Physiology (20 decks)

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