Laboratories of Life and Environmental Sciences, Faculty of Integrated Arts and Sciences, The University of Tokushima, Minami-Jyosanjima 1-1, Tokushima 770-8502, Japan.
Environ Toxicol Pharmacol. 2002 Mar;11(2):111-8. doi: 10.1016/s1382-6689(01)00112-0.
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 Ca(2+) (Ca(2+)), Cd(2+) (Cd(2+)) or both. It is difficult to detect the increase in Ca(2+) using Ca(2+)-chelator-based fluorescent Ca(2+) indicators in the presence of Cd(2+) because of their sensitivity to Cd(2+). Therefore, the study on membrane response such as Ca(2+)-dependent hyperpolarization gives a clue to reveal whether the Ca(2+) or Cd(2+) is increased. Cadmium at concentrations of 3 μM or more dose-dependently augmented fluo-3 fluorescence in rat thymocytes, presumably suggesting an increased Ca(2+). However, the membranes were not hyperpolarized although the cells possess Ca(2+)-dependent K(+) channels. One may argue that cadmium inhibits Ca(2+)-dependent K(+) channels so that cadmium fails to hyperpolarize the membranes. It is unlikely because the Ca(2+) increased by A23187, a calcium ionophore, elicited the hyperpolarization in the presence of Cd(2+). 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 Cd(2+) rather than the Ca(2+) in rat thymocytes, resulting in the induction of cytotoxicity.
镉是一种环境污染物，已被报道可诱导鼠淋巴细胞凋亡。为了揭示镉诱导凋亡的机制，一个重要的问题是镉是否增加细胞内钙离子浓度(Ca(2+))、镉离子(Cd(2+))或两者兼而有之。由于其对镉的敏感性，在存在镉的情况下，使用基于钙螯合剂的荧光钙指示剂检测Ca(2+)的增加是困难的。因此，对膜反应的研究，如钙依赖性超极化，为揭示是否增加了Ca(2+)或Cd(2+)提供了线索。3 μM 或更高浓度的镉剂量依赖性地增加了大鼠胸腺细胞中 flou-3 荧光，推测表明Ca(2+)增加。然而，尽管细胞具有钙依赖性钾通道，但膜没有超极化。人们可能会争辩说，镉抑制钙依赖性钾通道，因此镉不能使膜超极化。这是不太可能的，因为钙离子载体 A23187 增加的Ca(2+)在存在镉的情况下引起了超极化。此外，用溴化乙锭和 Annexin V-FITC 检查的镉诱导的细胞毒性的特征与 A23187 诱导的特征不同。综上所述，结论是镉的应用增加了Cd(2+)而不是大鼠胸腺细胞中的Ca(2+)，导致细胞毒性的诱导。
