Changes in expression of bcl-2 and bax in Syrian hamster embryo (SHE) cells exposed to ZnCl2.
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 micromol 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 micromol L(-1) ZnCl(2) 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 Zn(2+) 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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ESE, CNRS FRE 2635, Faculté des Sciences, Université de Metz, rue Général Delestraint, 57070 Metz, France.
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D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000378:metabolism; D002478:Cells, Cultured; D002712:Chlorides / Q000633:toxicity*; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D008647:Mesocricetus; D051379:Mice; D008969:Molecular Sequence Data; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D017967:Zinc Compounds / Q000633:toxicity*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C494827:Bax protein, mouse; C494828:Bax protein, rat; D002712:Chlorides; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2; D017967:Zinc Compounds; D051028:bcl-2-Associated X Protein; C016837:zinc chloride