Effects of cadmium on cellular calcium and proto-oncogene expression.
Effects of the carcinogenic metal cadmium on cellular calcium signalling and proto-oncogene expression were studied in mammalian cells. Cadmium ions interfered with bradykinin- and adenosinetriphosphate (ATP)-stimulated calcium transients in rat pheocromocytoma PC12 cells, but Cd2+ as such did not evoke intracellular Ca2+ spikes. At variance, cadmium ions caused a sustained elevation of intracellular free Ca2+ by inhibition of active calcium transport systems in various cell types. Problems of mutual interference of Ca2+ and Cd2+ analysis with the fluorescent probe Fura-2 could be overcome by the use of the fluorine 19 nuclear magnetic resonance (19F-NMR) probe acetoxymethyl ester of 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N'N'-tetraacetic acid (5F-BAPTA), which allows the measurement of free intracellular Ca2+, Cd2+ and other metal ions concurrently. Furthermore, the induction of the cellular protooncogenes c-fos and c-jun by Cd2+ was studied in PC12 cells. A dose of 0.5 microM Ca2+ sufficed to induce the c-Fos and c-Jun proteins within 30 min. These results support a model which suggests that cadmium stimulates cell proliferation by interference with intracellular calcium and induction of immediate early genes.
Department of Biology and Chemistry, University of Bremen, Germany.
S
S
Hechtenberg
T
T
Schäfer
J
J
Benters
D
D
Beyersmann
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D001920:Bradykinin / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002614:Chelating Agents; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D016257:Fura-2 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D009682:Magnetic Resonance Spectroscopy; D010673:Pheochromocytoma / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011519:Proto-Oncogenes / Q000235:genetics*; D051381:Rats; D014158:Transcription, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
D002614:Chelating Agents; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D002104:Cadmium; D004533:Egtazic Acid; C039877:5,5'-difluoro-1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D000255:Adenosine Triphosphate; D001920:Bradykinin; D002118:Calcium; D016257:Fura-2