Alterations in cytoskeletal protein sulfhydryls and cellular glutathione in cultured cells exposed to cadmium and nickel ions.
To understand the mechanisms of Cd2+ and Ni2+ cytotoxicity, we have studied the effects of these two metal ions on the organization of cytoskeletal elements, microtubules (MT) and microfilaments (MF), cytoskeletal protein sulfhydryls and cellular glutathione (GSH) in cultured 3T3 cells. At a metal ion dose that caused 95% inhibition of DNA synthesis, Cd2+ (10 microM, 16 h exposure) induced MT depolymerization whereas Ni2+ (2 mM, 20 h exposure) elicited MT aggregation and bundling. Under these conditions, Cd2+ and Ni2+ also caused MF aggregation and redistribution. Furthermore, exposure of cells to Cd2+ resulted in a dose-dependent increase in cytoskeletal protein sulfhydryls and cellular GSH levels. In contrast, treatment of cells with Ni2+ resulted in a dose-dependent decrease in cytoskeletal protein sulfhydryls as well as cellular GSH content. Time course studies showed that cells exposed to 10 microM Cd2+ exhibited a biphasic response in regulating their cytoskeletal protein sulfhydryls and cellular GSH, e.g. an initial decrease followed by a steady recovery and overshooting upon prolonged incubation. However, restoration of cytoskeletal protein sulfhydryls occurred approximately 2 h after commencement of cellular GSH recovery in Cd(2+)-treated cells. These results suggest that cellular GSH may play an important role in regulating cytoskeletal protein sulfhydryls. On the other hand, decrease of cellular GSH induced by Ni2+ might facilitate oxidation of cytoskeletal protein sulfhydryls and formation of disulfide bonds between individual MT polymers which would favor MT aggregation in Ni(2+)-exposed cells. In addition, we also demonstrated that elevation of cellular GSH in Cd(2+)-treated cells probably resulted from new GSH synthesis.
Li
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Department of Microbiology, Boston University School of Medicine, MA 02118.
Zhao
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Chou
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D016475:3T3 Cells; D008841:Actin Cytoskeleton / Q000187:drug effects*; D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000032:analysis / Q000187:drug effects*; D051379:Mice; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000187:drug effects*; D009532:Nickel / Q000633:toxicity*; D013438:Sulfhydryl Compounds / Q000032:analysis*; D014316:Tritium
D013438:Sulfhydryl Compounds; D002104:Cadmium; D014316:Tritium; D009532:Nickel; D004247:DNA; D005978:Glutathione