Alterations in Cytoskeletal Organization and Homeostasis of Cellular Thiols in Cadmium-Resistant Cells
| Autor: | Iih-Nan Chou, Wande Li, H. Kagan |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Drug Resistance
Biology Toxicology Microfilament 3T3 cells Mice chemistry.chemical_compound Cytosol medicine Animals Homeostasis Metallothionein Sulfhydryl Compounds Cytoskeleton Pharmacology 3T3 Cells Glutathione In vitro Cell biology medicine.anatomical_structure Microscopy Fluorescence chemistry Cadmium |
| Zdroj: | Toxicology and Applied Pharmacology. 126:114-123 |
| ISSN: | 0041-008X |
| DOI: | 10.1006/taap.1994.1097 |
| Popis: | To understand further the mechanisms of cadmium toxicity, cytoskeletal organization and homeostasis of cellular thiols were examined in cadmium-resistant cells isolated from Swiss mouse 3T3 cells by incubation in graded concentrations of CdCl2 (Cd2+) in the culture medium. Cd(2+)-resistant cells displayed profound alterations in their cytoskeletal organization characterized by the appearance of many elongated, tadpole-shaped cells with a high density of microtubules (MT) and microfilaments (MF), with the former being mainly distributed along the long axis of the cell. Exposure of Cd(2+)-resistant cells to 50 microM Cd2+ for 16 hr did not cause apparent cytoskeletal perturbations, whereas treatment of parental cells with 5 microM Cd2+ for the same duration produced a severe loss of MT and smeared patches of MF. Thus, the cytoskeleton of Cd(2+)-resistant cells is markedly more preserved and protected against Cd2+ damage than that of their parental counterparts. Cd(2+)-resistant cells contained a higher basal level of protein sulfhydryls (PSH) in both the cytoskeletal and cytosolic fractions than the parental cells. Exposure to 50 microM Cd2+ further increased cellular PSH contents, reaching 192 and 215% of the basal levels for the cytoskeletal and cytosolic fractions, respectively. Although 5 microM Cd2+ exposure also elevated the amounts of PSH in parental cells, the "absolute" values were still below the corresponding basal levels in Cd(2+)-resistant cells. Furthermore, Cd(2+)-resistant cells also exhibited enhanced basal levels of metallothionein and cellular glutathione (GSH), amounting to 19- and 2.1-fold of the parental basal levels, respectively. Thus, the Cd(2+)-resistant cells produced larger quantities of both protein and nonprotein thiol-containing elements than the parental cells. Interestingly, exposure of Cd(2+)-resistant cells to 50 microM Cd2+ also further increased metallothionein and cellular GSH to 178 and 138% of the basal levels, respectively. Based on the affinity of Cd2+ for sulfhydryls as a mechanism of Cd2+ toxicity, we propose that the coordinately increased levels of metallothionein, GSH, and PSH in Cd(2+)-resistant cells would provide a mechanistic basis for the homeostasis of cellular thiols which may collectively contribute to the cytoskeletal preservation by protecting the cytoskeleton from Cd2+ insult. |
| Databáze: | OpenAIRE |
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