Hechtenberg S, Beyersmann D
Department of Biology and Chemistry, University of Bremen, Germany.
Environ Health Perspect. 1994 Sep;102 Suppl 3(Suppl 3):265-7. doi: 10.1289/ehp.94102s3265.
The spatial and temporal regulation of intracellular free Ca2+ serves as a modulator of signal transduction pathways involved in cell growth and differentiation. Thus, interference of metals with intracellular Ca2+ homeostasis has been considered as a target of toxic action. We used the fluorescence indicator fura-2 to monitor the level of free Ca2+ in isolated bovine liver nuclei. Nuclei accumulated Ca2+ by an ATP-stimulated Ca2+ uptake system, which is sensitive to inhibition by thapsigargin, a specific inhibitor of intracellular Ca(2+)-ATPases. Preincubation of nuclei with nanomolar concentrations of free Cd2+ resulted in a dose-dependent inhibition of ATP-dependent nuclear Ca2+ uptake. We conclude that impairment of nuclear Ca2+ regulation caused by Cd2+ provokes alterations in nuclear events related to gene expression and cell proliferation.
细胞内游离钙离子（Ca2+）的时空调节作为细胞生长和分化相关信号转导途径的一种调节因子。因此，金属对细胞内Ca2+稳态的干扰被认为是毒性作用的一个靶点。我们使用荧光指示剂fura-2来监测分离的牛肝细胞核中游离Ca2+的水平。细胞核通过一个ATP刺激的Ca2+摄取系统积累Ca2+，该系统对毒胡萝卜素（一种细胞内Ca(2+)-ATP酶的特异性抑制剂）的抑制敏感。用纳摩尔浓度的游离Cd2+对细胞核进行预孵育导致ATP依赖性核Ca2+摄取呈剂量依赖性抑制。我们得出结论，Cd2+引起的核Ca2+调节受损引发了与基因表达和细胞增殖相关的核事件的改变。
