Rapid effect of bisphenol A on glutamate-induced Ca(2+)influx in hippocampal neurons of rats
Rapid effect of bisphenol A on glutamate-induced Ca(2+)influx in hippocampal neurons of rats
复制标题
双酚A对谷氨酸诱导的大鼠海马神经元Ca(2)内流的快速影响
DOI：
10.1016/j.mce.2019.01.024
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发表时间：
2019
影响因子：
4.1
通讯作者：
Xu Xiaohong
中科院分区：
文献类型：
--
作者：
Zhong Xiaoyu;Li Jishui;Zhuang Ziwei;Shen Qiaoqiao;Jiang Kesheng;Hu Yizhong;Wu Donghong;Xu Xiaohong
细胞内Ca ~（2+）信号在突触可塑性中起重要作用。本研究通过测定离体海马神经元胞内Ca ~（2+）荧光强度，探讨BPA对细胞内Ca ~（2+）浓度（[Ca ~（2+）]i）的影响。结果表明，BPA作用30 min对谷氨酸升高的[Ca 2 +]i产生剂量依赖性的双重效应：1-10 μM BPA抑制[Ca 2 +]i，但1-100 nM BPA增强谷氨酸升高的[Ca 2 +]i。BPA增强的[Ca ~（2+）] i可被NMDA受体拮抗剂阻断，并被雌激素相关受体γ（ERRγ）拮抗剂消除，而不被AR拮抗剂消除。MAPK/ERK和MAPK/p38抑制剂均能阻断BPA诱导的[Ca ~（2+）]i增加。BPA与17β-E2或DHT共同处理可消除17β-E2、DHT和BPA对谷氨酸升高[Ca 2 +]i的增强作用。这些结果表明，BPA在纳摩尔水平通过ERRγ介导的MAPK/ERK和MAPK/p38信号通路迅速增强NMDA受体的Ca 2+内流。然而，BPA拮抗雌激素和雄激素增强海马神经元NMDA受体介导的Ca 2+内流。
Intracellular Ca2+signaling plays an essential role in synaptic plasticity. This study examined the effect of BPA on concentration of intracellular Ca2+([Ca2+]i) by measuring fluorescence intensity of Ca2+in hippocampal neuronsin vitro. The results showed that BPA for 30 min exerted dose-dependently dual effects on glutamate-elevated [Ca2+]i: BPA at 1–10 μM suppressed but at 1–100 nM enhanced glutamate-raised [Ca2+]i. BPA-potentiated [Ca2+]iwas blocked by the antagonist of NMDA receptor and was eliminated by an estrogen-related receptor gamma (ERRγ) antagonist rather than an AR antagonist. Both inhibitors of MAPK/ERKs and MAPK/p38 blocked BPA-enhanced [Ca2+]i. Co-treatment of BPA with 17β-E2or DHT eliminated the enhancement of 17β-E2, DHT, and BPA in glutamate-elevated [Ca2+]i. These results suggest that BPA at nanomole level rapidly enhances Ca2+influx through NMDA receptor by ERRγ-mediated MAPK/ERKs and MAPK/p38 signaling pathways. However, BPA antagonizes both estrogen and androgen enhancing NMDA receptor-mediated Ca2+influx in hippocampal neurons.