Zinc-metallothionein levels are correlated with enhanced glucocorticoid responsiveness in mouse cells exposed to ZnCl(2), HgCl(2), and heat shock
| Autor: | Wendy Kennette, Olga Collins, James Koropatnick, Janice M. DeMoor |
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| Rok vydání: | 2001 |
| Předmět: |
Hot Temperature
Transcription Genetic Toxicology Cell Fractionation Dexamethasone Chloramphenicol acetyltransferase Mice Glucocorticoid receptor Receptors Glucocorticoid Cadmium Chloride Chlorides Genes Reporter Heat shock protein medicine Tumor Cells Cultured Metallothionein Animals Receptor Promoter Regions Genetic Glucocorticoids Cell Nucleus Chemistry Molecular biology In vitro Zinc Biochemistry Gene Expression Regulation Cell culture Zinc Compounds Mercuric Chloride Glucocorticoid Copper medicine.drug |
| Zdroj: | Toxicological sciences : an official journal of the Society of Toxicology. 64(1) |
| ISSN: | 1096-6080 |
| Popis: | Metallothioneins (MTs) are the major low molecular weight, zinc-binding proteins in mammalian cells. It has been hypothesized that they play a role in the function of zinc-dependent signal transduction proteins and transcription factors. We investigated the capacity of zinc and other metal ions and conditions to increase both Zn-associated MT levels and the receptiveness of cells to transcriptional activation mediated by the zinc-dependent glucocorticoid receptor (GR). We studied, in a GR-responsive mouse mammary-tumor cell line, the ability of dexamethasone (DEX) to stimulate transcription of a chloramphenicol acetyltransferase (CAT) gene controlled by a mouse mammary-tumor virus promoter. In cells pretreated with 20 to 100 microM ZnCl(2), DEX-induced CAT activity correlated with zinc-induced MT levels. However, 0.05 to 0.5 microM CdCl(2) had no effect on CAT activity, despite an increase in Cd-associated MT. Copper-associated MT was detected in cells treated with 20 microM CuCl(2,) but there was no change in the level of Zn-MT, nor was CAT activity altered in cells exposed to 5 to 20 microM CuCl(2). These results may reflect a functional difference between zinc-associated MT, and MT associated with other metals. Significantly more CAT activity was observed in both heat-shocked cells and in cells exposed to 40 or 50 nM HgCl(2). Although absolute amounts of MT were unchanged by these two treatments, a higher percentage of total cellular zinc was associated with the MT protein fractions after treatment. Changes in GR levels could not account for variations in CAT activity. These data indicate that hormonal signalling can be altered by exposure to metal salts and heat shock, and the effect is correlated with the level of Zn-MT. |
| Databáze: | OpenAIRE |
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