| Abstrakt: |
Cadmium, an environmental pollutant, has been reported to induce apoptosis in murine lymphocytes. To reveal the mechanism of cadmium-induced apoptosis, one of important questions is whether cadmium increases intracellular concentration of Ca2+ ([Ca2+]i), Cd2+ ([Cd2+]i) or both. It is difficult to detect the increase in [Ca2+]i using Ca2+-chelator-based fluorescent Ca2+ indicators in the presence of Cd2+ because of their sensitivity to Cd2+. Therefore, the study on membrane response such as Ca2+-dependent hyperpolarization gives a clue to reveal whether the [Ca2+]i or [Cd2+]i is increased. Cadmium at concentrations of 3 μM or more dose-dependently augmented fluo-3 fluorescence in rat thymocytes, presumably suggesting an increased [Ca2+]i. However, the membranes were not hyperpolarized although the cells possess Ca2+-dependent K+ channels. One may argue that cadmium inhibits Ca2+-dependent K+ channels so that cadmium fails to hyperpolarize the membranes. It is unlikely because the [Ca2+]i increased by A23187, a calcium ionophore, elicited the hyperpolarization in the presence of Cd2+. Furthermore, the profile of cytotoxicity induced by cadmium, examined by ethidium bromide and annexin V-FITC, was different from that induced by A23187. Taken together, it is concluded that the application of cadmium increases the [Cd2+]i rather than the [Ca2+]i in rat thymocytes, resulting in the induction of cytotoxicity. [Copyright &y& Elsevier] |
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