Modulation of intracellular calcium homeostasis by trimethyltin chloride in human tumour cells:: Neuroblastoma SY5Y and cervix adenocarcinoma HeLaS3
Modulation of intracellular calcium homeostasis by trimethyltin chloride in human tumour cells:: Neuroblastoma SY5Y and cervix adenocarcinoma HeLaS3
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DOI：
10.1016/j.tox.2005.05.029
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发表时间：
2005-12-01
期刊：
影响因子：
4.5
通讯作者：
Büsselberg, D
中科院分区：
文献类型：
--
作者：
Florea, AM;Splettstoesser, F;Büsselberg, D
细胞内Ca2+ ([Ca2+](i))水平的生理改变触发和/或调节细胞活动的多样性（如神经递质释放，突触可塑性，肌肉收缩，细胞增殖），而钙超载可能导致细胞毒性。先前，我们已经证明三甲基氯化锡（Me3SnCl； TMT）调节宫颈腺癌（HeLa S3）细胞中的钙稳态[Florea， a.m。， Dopp， E., Bfisselberg， D., 2005。TMT诱导HeLa细胞钙瞬态升高：反应的类型和水平。中国生物医学工程学报（英文版）；在这里，我们使用钙敏感染料（fluo-4/AM （fluo-4）和rhod-2/AM (rhod-2)）和激光扫描显微镜（LSM）比较三甲基氯化锡在神经母细胞瘤SY5Y和HeLa S3细胞中诱导的[Ca2+](i)-变化。tmt诱导神经母细胞瘤SY5Y和HeLa S3细胞钙升高。[Ca2+](i)上升到持续的平台或短暂的峰值。总体而言，检测到的最大钙升高平均为：0.5 μ M，接近125.6%；5亩M近似130.1%；500 μ M与HeLa S3细胞相似，为145%；0.5 μ M与HeLa S3细胞相似，为133.3%；5亩M类似136.1%；500 μ M与SY5Y神经母细胞瘤细胞相似，为147.1%。来源于内部储存的钙的增加并不明显依赖于外部溶液中钙的存在：HeLa细胞中类似于109%（不添加钙）和类似于117% （2 mM钙；5 μ M TMT）。这种差异在神经母细胞瘤SY5Y细胞中也类似，分别增加127%和136% （5 μ M TMT）。用rhod-2染色钙储存显示tmt诱导的[Ca2+](i)-减少，随后在两个细胞系的细胞核中钙浓度增加。我们的研究结果表明，暴露于三甲基锡化合物后，人类肿瘤细胞的毒性作用可能是由于[Ca2+]的升高(i)。2005爱思唯尔爱尔兰有限公司版权所有。
Physiological modifications of intracellular Ca2+ ([Ca2+](i)) levels trigger and/or regulate a diversity of cellular activities (e.g. neurotransmitter release, synaptic plasticity, muscular contraction, cell proliferation), while calcium overloads could result in cytotoxicity. Previously, we have shown that trimethyltin chloride (Me3SnCl; TMT) modulates calcium homeostasis in cervix adenocarcinoma (HeLa S3) cells [Florea, A.-M., Dopp, E., Bfisselberg, D., 2005. TMT induces elevated calcium transients in HeLa cells: types and levels of response. Cell Calcium 37, 252-258]. Here we compare [Ca2+](i)-changes induced by trimethyltin chloride in neuroblastoma SY5Y and HeLa S3 cells using calcium-sensitive dyes (fluo-4/AM (fluo-4) and rhod-2/AM (rhod-2)) and laser scanning microscopy (LSM). TMT-induced calcium elevations in neuroblastoma SY5Y as well as in HeLa S3 cells. [Ca2+](i) rose to a sustained plateau or to transient spikes. Overall, the detected averaged increase of the maximum calcium elevation were: 0.5 mu M similar to 125.6%; 5 mu M similar to 130.1%; 500 mu M similar to 145% in HeLa S3 cells and 0.5 mu M similar to 133.3%; 5 mu M similar to 136.1%; 500 mu M similar to 147.1% in neuroblastoma SY5Y cells. The calcium rise derived from internal stores did not significantly depend on the presence of calcium in the external solution: similar to 109% (no calcium added) versus similar to 117% (2 mM calcium; 5 mu M TMT) in HeLa cells. This difference was similar in neuroblastoma SY5Y cells, were similar to 127% versus similar to 136% increase (5 mu M TMT) were measured. Staining of calcium stores with rhod-2 showed a TMT-induced [Ca2+](i)-decrease in the stores followed by an increase of the calcium concentration in the nuclei of the two cell lines tested. Our results suggest that toxic effects in human tumour cells after exposure to trimethyltin compounds might be due to an elevation of [Ca2+](i). (c) 2005 Elsevier Ireland Ltd. All rights reserved.