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Effects of cadmium on cellular calcium and proto-oncogene expression
S Hechtenberg1, T Schäfer, J Benters
1Department of Biology and Chemistry, University of Bremen, Germany.
Annals of Clinical and Laboratory Science
|November 1, 1996
Summary
Cadmium exposure disrupts cellular calcium (Ca2+) signaling and triggers the expression of proto-oncogenes c-fos and c-jun in mammalian cells. This interference with calcium and gene induction may promote cell proliferation.
Area of Science:
- Cell Biology
- Toxicology
- Molecular Biology
Background:
- Cadmium (Cd2+) is a carcinogenic metal with known cellular effects.
- Understanding cadmium's impact on calcium signaling and gene expression is crucial for assessing its health risks.
Purpose of the Study:
- To investigate the effects of cadmium on cellular calcium (Ca2+) signaling.
- To examine the induction of proto-oncogenes c-fos and c-jun by cadmium in mammalian cells.
Main Methods:
- Utilized rat pheochromocytoma PC12 cells.
- Employed fluorine 19 nuclear magnetic resonance (19F-NMR) probe 5F-BAPTA for precise metal ion measurement.
- Assessed intracellular Ca2+ and Cd2+ levels.
- Monitored the expression of c-Fos and c-Jun proteins.
Main Results:
- Cadmium ions interfered with bradykinin- and adenosine triphosphate (ATP)-stimulated calcium transients.
- Cadmium caused a sustained elevation of intracellular free Ca2+ by inhibiting calcium transport.
- A low dose of cadmium (0.5 microM) induced c-Fos and c-Jun proteins within 30 minutes.
Conclusions:
- Cadmium disrupts normal cellular calcium homeostasis.
- Cadmium induces immediate early genes, suggesting a role in cell proliferation.
- These findings support a model where cadmium stimulates cell proliferation via calcium interference and proto-oncogene induction.