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- W2065941352 abstract "Cytoskeletal perturbations have been associated with exposures to a variety of toxic agents as well as a number of human pathological conditions. We have observed dramatic alterations in the organization of microtubules (MT), a major component of the cytoskeleton, in 3T3 cells exposed to Ni2+. Severe perinuclear bundling and aggregation of MT occurred in both a time- and dose-dependent fashion, and this MT damage was reversible upon removal of Ni2+ from the culture media. To understand the mechanism of the Ni2+-induced MT change, we investigated the effect of Ni2+ (0.01 to 3.0 mm) on in vitro tubulin polymerization. Ni2+ at lower concentrations (0.01 to 1.0 mm) had little or no significant effect on the kinetics of MT polymerization. In contrast, in the presence of 1.5 to 2.0 mm Ni2+, a significant promoting effect on both the rate and the final extent of polymerization was observed. However, at Ni2+ concentrations higher than 2.0 mm, such stimulatory effect on the rate and the final extent of tubulin polymerization declined. Furthermore, the promoting effects of Ni2+ on MT polymerization were accompanied by a significant decrease in the lag period. Electron microscopic examination of samples of the polymerization product showed that MT, polymerized in the presence of 2.0 mm Ni2+, appeared more numerous and shorter (1.10 ± 1.02 μm) than those of control (3.81 ± 2.29 μm; p < 0.005). This was probably a direct result of an increase in the number of initiation centers in the presence of Ni2+ as a consequence of the decreased critical concentration (7%, p < 0.05) necessary for polymerization to occur. Our results suggest that Ni2+ may exert its toxic effect on MT in cultured cells by altering the normal kinetics of MT polymerization." @default.
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- W2065941352 date "1990-11-01" @default.
- W2065941352 modified "2023-09-26" @default.
- W2065941352 title "Studies on the mechanisms of Ni2+-induced cell injury: I. Effects of Ni2+ on microtubules" @default.
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- W2065941352 doi "https://doi.org/10.1016/0041-008x(90)90241-l" @default.
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