Abstract
Zinc is involved in many physiological processes and plays a critical role in functional and structural cells. Zinc at concentrations ranging from 100 to 150 μmol L−1 has been shown to induce morphological transformation of Syrian hamster embryo (SHE) cells. At these concentrations, zinc inhibited apoptosis in SHE cells. The objective of this study was to elucidate the mechanisms of action of zinc on the apoptotic pathway. Effects of 100 and 150 μmol L−1 ZnCl2 on the expression of two members of the Bcl-2 family of proteins and on the transcription factor c-Myc in SHE cells was investigated using RT-PCR. No effect on the proto-oncogene c-myc was observed. Up-regulation of bcl-2 expression was found and bax expression was reduced. These changes have been corroborated by immunoblotting. Effects of Zn2+ on bcl-2/bax ratio were confirmed in apoptotic camptothecin-treated SHE cells. Cloned and sequenced cDNAs obtained from RT-PCR amplifications allowed us to check the RT-PCR products encoded the expected proteins. This study demonstrated that zinc acts in the early phases of the apoptotic process by modification of the bcl-2/bax ratio in normal and apoptotic SHE cells.
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Acknowledgments
The authors thank Dr P. Poupin for constructive discussions and Pr A. Hammond for assistance in revising the English form of this paper. They are grateful to Dr Methlin and his colleagues from the “Claude Bernard Hospital—Departement de Radiotherapie et de Chimiotherapie” for preparation of irradiated SHE cells. This study was funded by the French Ministry of Research and Direction for Prevention of Pollution and Environmental Risk of the Ministry of the Environment. The authors declare that the experiments comply with the current law in France and with safety requirements.
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Maire, M.A., Rast, C., Pagnout, C. et al. Changes in expression of bcl-2 and bax in Syrian hamster embryo (SHE) cells exposed to ZnCl2. Arch Toxicol 79, 90–101 (2005). https://doi.org/10.1007/s00204-004-0611-y
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DOI: https://doi.org/10.1007/s00204-004-0611-y