Elevation of Intracellular Ca2+ Level by Triclosan in Rat Thymic Lymphocytes: Increase in Membrane Ca2+ Permeability and Induction of Intracellular Ca2+ Release
Elevation of Intracellular Ca2+ Level by Triclosan in Rat Thymic Lymphocytes: Increase in Membrane Ca2+ Permeability and Induction of Intracellular Ca2+ Release
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DOI：
10.1248/jhs.57.540
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发表时间：
2011-12-01
影响因子：
--
通讯作者：
Oyama, Yasuo
中科院分区：
文献类型：
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作者：
Tamura, Ikumi;Saito, Minoru;Oyama, Yasuo
三氯生是一种用于家居用品和个人护理产品的抗菌剂。由于野生动物和人类的体内可能含有这种化合物，三氯生的毒性作用是可能的，也是值得怀疑的。因此，我们用荧光探针的细胞学技术检测了三氯生对大鼠胸腺细胞内钙离子浓度的影响。1-10mU M的三氯生可显著增强检测钙离子的Fluo-3荧光强度，表明细胞内钙离子浓度升高。加入外源Ca~(2+)后，Fluo-3荧光增强更明显，且呈剂量依赖关系。相反，外源钙离子的去除大大减弱了三氯生对Fluo-3荧光的增强作用。这些结果表明，三氯生处理允许外部钙离子通过细胞膜。这一现象并非钙离子所特有，因为外加的Mn2+猝灭了三氯生诱导的Fluo-3荧光增强，表明三氯生也可以介导Mn2+的跨膜渗透。因此，这些结果表明，三氯生增加了膜对二价金属离子的通透性。此外，三氯生诱导细胞内钙离子释放，因为在三氯生处理后，即使在没有小牛体外的条件下，Fluo-3的荧光强度仍然略有增加。此外，在无钙条件下，A23187从细胞内钙库中清除钙离子时，三氯生不会增加Fluo-3的荧光强度。综上所述，这些数据表明，微摩尔浓度的三氯生影响胸腺细胞内钙稳态，可能导致细胞功能障碍。
Triclosan is an antibacterial agent used in household items and personal care products. Because wild animals and humans can harbor this compound in their systems, the toxic effects of triclosan are a possibility and are suspected. Therefore, we examined the effects of triclosan on intracellular Ca2+ concentration in rat thymocytes by cytometric techniques using fluorescent probes. Triclosan doses of 1-10 mu M significantly increased the intensity of Ca2+-detecting Fluo-3 fluorescence, indicating an increase in intracellular Ca2+ concentrations. The augmentation of Fluo-3 fluorescence became more profound in a dose-dependent manner after the addition of an external source of Ca2+. Conversely, the removal of external Ca2+ greatly attenuated the triclosan-induced augmentation of Fluo-3 fluorescence. These results suggest that triclosan treatment allows external Ca2+ to pass through cell membranes. This phenomenon was not specific for Ca2+ because external Mn2+ quenched the triclosan-induced augmentation of Fluo-3 fluorescence, indicating that triclosan can also mediate Mn2+ permeation across membranes. Therefore, these results suggest that triclosan increases membrane permeability to divalent metal cations. Furthermore, triclosan induces Ca2+ release from intracellular stores because the Fluo-3 fluorescence intensity still increased slightly after triclosan treatment, even under conditions free from external Calf. Additionally, triclosan did not increase the intensity of Fluo-3 fluorescence when Ca2+ was depleted from intracellular Ca2+ stores by A23187 under the external Ca2+-free condition. Taken together, these data suggest that micromolar concentrations of triclosan affect intracellular Ca2+ homeostasis in thymocytes, possibly resulting in cellular malfunction.