cAMP increasing agents prevent the stimulation of heat-shock protein 70 (HSP70) gene expression by cadmium chloride in human myeloid cell lines

Treatment of U-937 human promonocytic cells with the cAMP increasing agents isoproterenol plus theophylline decreased the basal level of heat-shock protein 70 (HSP70) mRNA. In addition, the cAMP increasing agents attenuated the increase in HSP70 mRNA and protein levels produced by cadmium chloride in U-937 and other human myeloid cell lines, reduced the capacity of cadmium treatment to generate stress-tolerance, and attenuated the cadmium-produced stimulation of heat-shock factor (HSF) binding activity. By contrast, isoproterenol plus theophylline failed to attenuate the stimulation of HSP70 gene expression and HSF binding activity caused by heat-shock. Isoproterenol plus theophylline did not prevent the uptake of cadmium into the cells, and increased to a similar extent the intracellular cAMP levels in cadmium- and heat-treated cells. The cAMP increasing agents reduced the induction by cadmium of the HSP27 stress gene, but failed to attenuate other cadmium-elicited stress reactions such as the inhibition of total protein synthesis. It is concluded that cAMP does not inhibit the stress response as a whole, but it interferes with some step of the pathway by which cadmium specifically stimulates HSF binding activity and as a consequence HSP70 gene expression, in human myeloid cell lines.