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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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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.
Thermotolerance: • After an initial heating treatment it is the development of a resistance to subsequent heating treatments.
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: • 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!!!!! • Hypoxia • Viral infections • Oxidative stress • Arsenite • Ethanol
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 • These puffs are translated into heat shock proteins (Hsp) • After about 10 min. The puffs subside
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 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 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 • Hsp 27 is located on: • Chromosome 11 • Arm q • 22nd and 23rd gene
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 • 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.
Apoptosis • By stopping activation of cas3 the cell does not undergo apoptosis therefore preventing cell suicide.
Stress Cytochrome C Caspase 9 Caspase 9/Apaf 1 complex Apaf 1 Hsp27 Activated Cas3 Apoptosis
Hsp27 • From this figure we see that hsp27 can inhibit the cytochrome c mediated activation of cas3.
Hsp 27 • Not only can hsp27 bind with cas3 in cell free experiment but it also binds in vivo.
What About Radiation? • Unfortunately radiation inhibits the association of hsp 27 with cas3.
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? • 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.
