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.
Vilaboa
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NE
Centro de Investigaciones Biológicas, CSIC, Velázquez, Madrid, Spain.
Calle
C
C
Pérez
C
C
de Blas
E
E
García-Bermejo
L
L
Aller
P
P
D001483:Base Sequence; D002104:Cadmium / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D019256:Cadmium Chloride; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002712:Chlorides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006358:Hot Temperature; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D007938:Leukemia; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D013806:Theophylline / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014633:Valine / Q000378:metabolism
D002712:Chlorides; D018840:HSP70 Heat-Shock Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D002104:Cadmium; D013806:Theophylline; D000242:Cyclic AMP; D014633:Valine; D019256:Cadmium Chloride; D007545:Isoproterenol