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Heat Shock Proteins: Psychotherapy for the Cell

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Heat Shock Proteins: Psychotherapy for the Cell. Kelly Andringa November 8, 2000. 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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Presentation Transcript
historically
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.
thermotolerance
Thermotolerance:
  • After an initial heating treatment it is the development of a resistance to subsequent heating treatments.
heat shock proteins
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.
currently
Currently:
  • More recent discoveries have been made that show heat shock proteins are induced by a variety of stresses not just heating (hyperthermia).
cells under stress
Cells Under Stress!!!!!
  • Hypoxia
  • Viral infections
  • Oxidative stress
  • Arsenite
  • Ethanol
first experiments
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
experiment continued
Experiment Continued
  • These puffs are translated into heat shock proteins (Hsp)
  • After about 10 min. The puffs subside
experiment continued9
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.
heat shock protein 27
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.
heat shock protein 2711
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)
map of hsp27
Map of Hsp27
  • Hsp 27 is located on:
    • Chromosome 11
    • Arm q
    • 22nd and 23rd gene
cell stress
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.
apoptosis
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.
apoptosis15
Apoptosis
  • By stopping activation of cas3 the cell does not undergo apoptosis therefore preventing cell suicide.
slide16

Stress

Cytochrome C

Caspase 9

Caspase 9/Apaf 1 complex

Apaf 1

Hsp27

Activated Cas3

Apoptosis

hsp27
Hsp27
  • From this figure we see that hsp27 can inhibit the cytochrome c mediated activation of cas3.
hsp 27
Hsp 27
  • Not only can hsp27 bind with cas3 in cell free experiment but it also binds in vivo.
what about radiation
What About Radiation?
  • Unfortunately radiation inhibits the association of hsp 27 with cas3.
final thoughts
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.
why psychotherapy
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.