Activation of Ca²⁺-Dependent Processes during Heat Shock: Role in Cell Thermoresistance

In this brief review, it is proposed that some Ca²⁺-dependent processes are induced upon subjecting cells to hyperthermic temperature, and play an essential role in the final cell responses. The triggering signal does not involve external Ca²⁺. Instead, it is most likely to be generated by a redistribution of Ca²⁺ between the internal pools. A role for heat-induced Ca²⁺-dependent processes is supported by findings that <tex-math>${\rm Ca}^{2+}\text{-active}$</tex-math> agents such as chelators, ionophores, or anticalmodulin drugs modify the cytotoxic action of hyperthermia and that some heat shock proteins are calmodulin-binding proteins. Furthermore, within minutes at hyperthermic temperature, changes are observed in the pattern of phosphoproteins suggesting that heat shock activates kinase or phosphatase activities, processes which are often mediated by Ca²⁺. Suggestive evidence that these phosphorylation events are determinants of cell thermoresistance is provided by the fact that one of these proteins whose phosphorylation changes rapidly upon hyperthermia is a heat shock protein (HSP28) and that the content of HSP28 is elevated not only in thermotolerant cells but also in a family of thermoresistant variants isolated after mutagenesis of Chinese hamster cells.