Heat Shock Proteins: Psychotherapy for the Cell

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Heat Shock Proteins Psychotherapy for the Cell

• Kelly Andringa
• November 8, 2000

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Historically

• Heat shock proteins were first discovered when
  cells were heated and proteins of certain
  molecular weight were produced.
• These proteins appeared with the development of
  cell thermotolerance.

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Thermotolerance

• After an initial heating treatment it is the
  development of a resistance to subsequent heating
  treatments.

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Heat Shock Proteins

• In this picture the proteins were run on a
  polyacrylamide gel which shows the pattern of
  protein development after heat treatment of 45
  degrees for 20 min.

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Currently

• More recent discoveries have been made that show
  heat shock proteins are induced by a variety of
  stresses not just heating (hyperthermia).

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Cells Under Stress!!!!!

• Hypoxia
• Viral infections
• Oxidative stress
• Arsenite
• Ethanol

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First Experiments

• The first experiments were done with Drosophila
  Melanogaster larvae
• These larvae were put in a brief temperature
  increase and the chromosomes were viewed under
  the microscope
• What was noticed was the induction of heat shock
  puffs on the DNA after one minute

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Experiment Continued

• These puffs are translated into heat shock
  proteins (Hsp)
• After about 10 min. The puffs subside

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Experiment Continued

• After heat shock (or another stress) the
  synthesis of heat shock proteins is increased
  while the synthesis of other proteins ceases.
• Once the heat shock puffs subside the increase in
  Hsp synthesis remains the same.

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Heat Shock Protein 27

• Heat shock protein 27 or hsp27 is believed to
  help regulate many things. One of its
  interesting jobs is to negatively regulate
  apoptosis.
• Over expression of hsp27 has been shown to
  protect cells against necrosis initiated by
  anti-cancer drugs, oxidative stress, ect.

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Heat Shock Protein 27

• Molecular weight of 27 kDa
• Located on chromosome 11q22-q23
• 199 amino acid sequence
• 2 exons
• Produces a 1 kb transcript (in vitro)

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Map of Hsp27

• Hsp 27 is located on
• Chromosome 11
• Arm q
• 22nd and 23rd gene

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Cell Stress

• Stress in cells causes the arrest of the cell
  cycle and activation of DNA repair.
• In instances of irreparable DNA damage the cell
  responds with induction of apoptosis.

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Apoptosis

• As we learned earlier stress induces release of
  cytochrome c which activates caspase 9 which
  binds with Apaf 1 to activate procaspase-3 (cas3)
  the executioner caspase.
• Hsp 27 inhibits activation of cas3 by binding and
  blocking caspase 9.

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Apoptosis

• By stopping activation of cas3 the cell does not
  undergo apoptosis therefore preventing cell
  suicide.

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Stress
Cytochrome C
Caspase 9
Caspase 9/Apaf 1 complex
Apaf 1
Hsp27
Activated Cas3
Apoptosis
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Hsp27

• From this figure we see that hsp27 can inhibit
  the cytochrome c mediated activation of cas3.

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Hsp 27

• Not only can hsp27 bind with cas3 in cell free
  experiment but it also binds in vivo.

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What About Radiation?

• Unfortunately radiation inhibits the association
  of hsp 27 with cas3.

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Final Thoughts

• We have seen that hsp 27 inhibits activation of
  cas3 stopping apoptosis.
• These findings may be useful because over
  expression of hsp27 in normal tissues may help
  survival of these normal tissues in chemotherapy
  treatments.

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Why Psychotherapy?

• Psychotherapy is used to help people with their
  problems.
• Hsp 27 helps cells with their stress situations
  and helps them to not commit cell suicide.

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Thank You!