The orphan nuclear receptor Nur77 plays a vital role in BPA-induced PC12 cell apoptosis
The orphan nuclear receptor Nur77 plays a vital role in BPA-induced PC12 cell apoptosis
复制标题
孤儿核受体Nur77在BPA诱导的PC12细胞凋亡中发挥重要作用
DOI：
10.1016/j.ecoenv.2021.112026
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发表时间：
2021-02-11
影响因子：
6.8
通讯作者：
Gao, Zhixian
中科院分区：
文献类型：
--
作者：
Zhang, Yingchun;Li, Shuang;Gao, Zhixian
双酚A（BPA）是一种典型的环境内分泌干扰物，可通过皮肤接触、呼吸、饮食等多种途径迁移到生物体内。BPA的生殖毒性和神经毒性已被多项毒理学研究证实。然而，BPA的神经毒性仍然存在争议。本研究以PC 12细胞为模型，探讨BPA诱导神经细胞凋亡的机制。BPA暴露降低了细胞活力，改变了细胞形态，并加剧了细胞内乳酸脱氢酶（LDH）的释放，细胞内Ca 2+浓度，活性氧（ROS）水平，细胞凋亡和线粒体跨膜电位（Δ Psi m）的降低。Western blot和RT-qPCR检测结果显示，BPA组Nur 77表达下调，NF-κ B/Bcl-2蛋白表达下调，细胞凋亡标志物c-caspase 3表达上调。然而，这些变化被显着逆转与nur 77蛋白的上调，通过引入质粒携带nur 77基因。这些结果表明BPA诱导的细胞凋亡与Nur 77介导的NF-κ B/Bcl-2通路的抑制密切相关。
Bisphenol A (BPA) is a typical environmental endocrine disruptor that can migrate into organisms through skin contact, breathing, diet and various other approaches. The reproductive toxicity and neurotoxicity of BPA has been confirmed by several toxicological studies. However, the neurotoxicity of BPA is still controversial. In the present study, we used PC12 cells as a model to investigate the mechanism of BPA-induced neuronal apoptosis. BPA exposure reduced cell viability, altered cell morphology and aggravated intracellular Lactate dehydrogenase (LDH) release, intracellular Ca2+ concentration, Reactive oxygen species (ROS) levels, apoptosis and the reduction in the mitochondrial transmembrane potential (Delta Psi m). Moreover, the results of the Western blot (WB) and Real-time quantitative polymerase chain reaction (RT-qPCR) assays indicated that the expression levels of Nur77 in the BPA group were down-regulated and accompanied by the downregulation of the NF-kappa b/Bcl-2 proteins and the upregulation of cleaved-caspase 3, which is a marker of apoptosis. However, these changes were significantly reversed with the upregulation of the Nur77 protein by introducing plasmids carrying the nur77 gene. These results indicated that BPA-induced apoptosis was closely related to Nur77-mediated inhibition of the NF-kappa b/Bcl-2 pathway.