When cells from a wide variety of organisms, including man, are exposed to elevated temperatures, they preferentially synthesize a specific set of polypeptides known as heat shock proteins (HSP's). Although the function of these proteins is not known, they are presumed to be important because their sequences are highly conserved and because some of them are abundant proteins under normal culture conditions. Numerous studies have also shown a positive correlation between the degree of induction and resistance of cells to killing by hyperthermia. We have shown that synthesis, degradation and intracellular levels of the two major HSP's in murine cells (85K and 69K) are regulated in response to extracellular glucose concentration. Several lines of evidence indicate that glucose may regulate HSP levels through its role in energy production. The proposed project would systematically survey intermediary metabolites related to glucose for effects on HSP synthesis and degradation. The goal would be to identify the physiological regulators of HSP levels. It would also be determined how the availability of substrates for energy production, e.g., glucose, glutamine and pyruvate, affect HSP synthesis and cell viability after heat shock and whether heat shock affects the concentrations of presumptive regulatory metabolites. Finally, the 85K HSP which we have purified will be examined for its ability to alter the concentration of presumptive regulatory metabolites in vitro.
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