Apoptosis Flashcards

1
Q

Apoptosis general description

A

Regulated cell suicide
Via intrinsic enzymes —> acting on DNA, nuclear and cytoplasmic proteins.
—> then forms ‘apoptotic bodies’ = cytoplasm and nucleus—> these are easy targets for phagocytosis

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2
Q

List 5 situations of apoptosis in physiological situations

A
  1. Embryogenesis —> different phases
  2. Growth factor deprivation —> cells which are sensitive to hormone stimulation do not receive the hormones they need undergo apoptosis- (eg Lymphocytes: antigens + cytokines / neurons: nerve growth factor

3 Cell loss in proliferating cell population: —> eg lymphocytes in the bone marrow and thymus

  1. Elimination of self-reactive lymphocytes
  2. Death of host cells that have served their purpose —> eg neutrophils after acute inflammatory response and lymphocytes after immune response
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3
Q

List three apoptosis in pathological conditions

A
  1. DNA damage from (radiation, cytotoxic anticancer drugs and hypoxia), If repair mechanism cannot cope with injury —> ‘tumour-suppressor gene p53 induces apoptosis’
  2. Accumulation of misfiled proteins: ( from mutations in the genes encoding the proteins or extrinsic factors (free radicals) = apoptosis via the proteins accumulating on ER = the condition called ER stress —> apoptosis cell death
  3. Infections, in particular viral infections
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4
Q

Explain apoptotic cell death histologically morphologically

A

Process of creating apoptotic bodies

  • condensation and fragmentation of the nucleus (Pyknosis and karyorrhexis)
  • Blebbing of the plasma membrane (the cell’s cytoskeleton breaks up and causes the membrane to bulge outward)

Thus histologically apoptotic cells appear

  • round or oval mass
  • Intensely eosinophilic cytoplasm with fragments of dense nuclear chromatin
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5
Q

Mechanisms of apoptosis

A
  • caspases enzyme activation = cleave proteins apart
  • Proenzyme caspases —> activated caspases = two pathways
    a) mitochondrial pathway
    b) Death receptor pathway
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6
Q

Explain the mitochondrial pathway

A

major pathway
Increased mitochondrial membrane permeability = pro-apoptotic molecules releasing from inter membrane space into —> cytoplasm

BCL2 family proteins control release of pro-apoptotic proteins = three families of molecules
Anti-apoptotic
Pro-apoptotic
Sensors

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7
Q

Explain anti-apoptotic molecules

A

Lx = outer mitochondrial membranes, cytosol + ER membranes

Fx= keeping mitochondrial outer membrane impermeable = prevent leakage of cytochrome C and other death-inducing proteins into cytosol

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8
Q

Explain pro-apoptotic molecules

A

Fx = when activated
oligomerise (combine together like Voltron) with outer mitochondria membrane = promoting increase in mitochondrial outer permeability

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9
Q

Explain Sensor molecules

A

Fx = sense cellular stress + damage

= regulate balance between anti-apoptotic and pro apoptotic

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10
Q

What stimulates the production of anti-apoptotic proteins?

A

Growth factors and other survival signals

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11
Q

When and how do pro-apoptotic proteins activate?

A

cells deprived of survival signals
DNA is damaged
Misfolded proteins induce —> ER stress

The things above activate the sensor molecules which in turn activate the pro-apoptotic proteins.

Important note - sensors may also bind to + block anti-apoptotic proteins.

Net result =
- increased permeability of mitochondria outer membrane —> allowing mitochondria proteins that can activate the caspase cascade.

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12
Q

Explain the extrinsic pathway of apoptosis

A

Plasma membrane death receptors
Present on variety of cells

Best known receptor = type 1 TNF receptors and Fas

Fas Ligand on T cells attaches to Fas receptor = forming a binding site for an adaptor protein called FADD which activate intracytoplasmic Caspases

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13
Q

Explain the final phase of apoptosis

A

Both pathways converge here

DNA cleavage + degradation

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14
Q

Disorders associated with dysregulated apoptosis

A

“Too little or too much”
Too little = too many abnormal cells survive = cancer
Or lymphocytes which react to self- antigens are not apoptosised = autoimmune disorders

Increased apoptosis
neurodegenerative disease
Ischaemic injury
Death of virus-infected cells

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