Elucldation of the mechanism for the development of thermotolerance in cells

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The molecular mechanism for translent developmental thermotolerance is still obscue, but many studies suggest that heat shock proteins (Hsps), especially Hsp70, are involved in the development thermotolerance. The correlation between Hsps and thermotolerance has been extensively studied in in vitro systems using cultured mammalian cells so far. We investigated the relationship between Hsp40/Hsp70 synthesis and the development of thermotolerance using mouse squamous cell carcinoma in vivo. These results obtained in vivo were very similar to those in vitro. Next We examine the induction of apotosis on hyperthermia using transplanted mouse tumor. These results suggested that the induction of apotosis is closely related to the cell death caused by hyperthermia. And the antitumor effect of hyperthermia and OK-432 therapy is not ascribable to the induction of apotosis. Furthermore we investigated the induction of mammalian Hsp40 by various enviromental stresses in HeLa cells and the constitutive expression of Hsp40 in adult mouse tissues in comparison with those of Hsp70. induction pattems of Hsp40 and Hsp70 were very similar. Heat shock was the most effective. Azetidine carboxylic acid, sodium arsenite and ethanol were moderate stresses for the induction Hsps. lnterestingly, dinitrophenol and hydrogen peroxide could induce Hsp40 but not Hsp70. These results suggest differential regulation of the transcriptional activation between Hsp40 and Hsp70. Both Hsp40 and Hsp70 were expressed in all mouse tissues examined with some variation. However, Hsp40 was expressed in the testies at remarkably higher level as compared with other tissues. These results suggested that both Hsp70 and Hsp40 are ubiquitously expressed and have essential and indispensable functions as molecular chaperones and that Hsp40 in the testies might have some specific function in addition to the molecular chaperone activity.