Membrane hyperpolarization and depolarization of rat thymocytes by azoxystrobin, a post harvest fungicide
Membrane hyperpolarization and depolarization of rat thymocytes by azoxystrobin, a post harvest fungicide
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DOI：
10.1016/j.cbi.2019.01.006
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发表时间：
2019-02-25
影响因子：
5.1
通讯作者：
Oyama, Yasuo
中科院分区：
文献类型：
--
作者：
Imura, Naohiro;Ae, Masamichi;Oyama, Yasuo
嘧菌酯是一种广谱杀菌剂，在农业生产中的应用日益广泛。2018年，在日本，在一批用于食品的澳大利亚大麦中检测到了五倍于正常限度的嘧菌酯。因此，需要仔细检查嘧菌酯的作用，以预测人体潜在的不良反应。在这项研究中，嘧菌酯对胸腺细胞的膜电位和细胞内Ca 2+水平的影响已被光化学检测使用流式细胞仪。嘧菌酯超极化质膜电位。这种超极化似乎是由于Ca2+依赖性K（+）通道的激活，因为细胞外Ca2+的去除和加入Charybdotoxin都减弱了观察到的超极化。在奎宁（一种阻断钙依赖性钾通道的抗疟疾药物）存在下，嘧菌酯反而使细胞膜去极化。嘧菌酯以浓度依赖性方式通过细胞外Ca2+的流入和细胞内Ca2+的释放来增加细胞内Ca2+水平，如通过在细胞外Ca2+不存在的情况下减少嘧菌酯诱导的反应所证实的。微摩尔浓度的嘧菌酯可能会改变胸腺细胞的膜离子渗透性。由于膜电位和细胞内Ca2+水平的变化发生在典型的生理淋巴细胞反应，嘧菌酯可能会干扰淋巴细胞功能。
Azoxystrobin, a broad-spectrum fungicide, has been increasingly used in the agricultural industry. In Japan in 2018, azoxystrobin at five times the normal limit was detected in a shipment of Australian barley that had been used in food products. Therefore, the effects of azoxystrobin need to be carefully examined to predict potential adverse reactions in humans. In this study, the effects of azoxystrobin on the membrane potential and intracellular Ca2+ levels of thymocytes have been photochemically examined using flow cytometry. Azoxystrobin hyperpolarized plasma membrane potential. This hyperpolarization appeared to be due to the activation of Ca2+-dependent K(+)channels, as both the removal of extracellular Ca2+ and addition of charybdotoxin attenuated the observed hyperpolarization. In the presence of quinine, an anti-malarial drug that blocks Ca2+-dependent K+ channels, azoxystrobin depolarized the membranes instead. Azoxystrobin increased intracellular Ca2+ levels in a concentration-dependent manner through the influx of extracellular Ca2+ and intracellular release of Ca2+, as confirmed by reduction in azoxystrobin-induced response in the absence of extracellular Ca2+. It appears likely that azoxystrobin at micromolar concentrations modifies membrane ion permeability in thymocytes. Since changes in membrane potential and intracellular Ca2+ levels occur during typical physiological lymphocyte responses, azoxystrobin may disturb lymphocyte function.