He Qing-Zhi, Zhu Bi-Qi, Xu Xiao-Na, Zeng Huai-Cai
Department of Occupational and Environmental Health, Guilin Medical University, Guilin, China.
Department of Preventive Medicine, University of South China, Hengyang, China.
J Biochem Mol Toxicol. 2021 Jun;35(6):1-11. doi: 10.1002/jbt.22775. Epub 2021 Mar 22.
Bisphenol S (BPS) is associated with neurotoxicity, but its molecular mechanisms are unclear. Our aim was to investigate the role of the brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB)/cAMP-response element-binding protein (CREB) signaling pathway in BPS-induced cytotoxicity in SK-N-SH cells. The cells were treated with various concentrations of BPS, and cell viability, apoptosis rate, mitochondrial membrane potential (MMP), and the BDNF, cleaved-caspase-3, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), TrkB, CREB, and phospho-CREB (p-CREB) levels were determined. The effects of pretreatment with the TrkB activator 7,8-dihydroxyflavone (7,8-DHF) were also explored. BPS decreased SK-N-SH cell viability and altered their morphology. Their apoptosis rate was increased, as were the levels of the proapoptotic proteins Bax and cleaved-caspase-3, but MMP was decreased. Thus, BPS may induce mitochondria-dependent apoptosis pathways. BPS also reduced the BDNF, TrkB, and p-CREB levels, and pretreatment with 7,8-DHF alleviated its cytotoxic effects. Thus, BPS-induced cytotoxicity might be mediated by the BDNF/TrkB/CREB signaling pathway.
双酚S（BPS）与神经毒性有关，但其分子机制尚不清楚。我们的目的是研究脑源性神经营养因子（BDNF）/酪氨酸激酶B（TrkB）/环磷酸腺苷反应元件结合蛋白（CREB）信号通路在BPS诱导的SK-N-SH细胞毒性中的作用。用不同浓度的BPS处理细胞，测定细胞活力、凋亡率、线粒体膜电位（MMP）以及BDNF、裂解的半胱天冬酶-3、B细胞淋巴瘤2（Bcl-2）、Bcl-2相关X蛋白（Bax）、TrkB、CREB和磷酸化CREB（p-CREB）的水平。还探讨了用TrkB激活剂7,8-二羟基黄酮（7,8-DHF）预处理的效果。BPS降低了SK-N-SH细胞的活力并改变了其形态。细胞凋亡率增加，促凋亡蛋白Bax和裂解的半胱天冬酶-3的水平也增加，但MMP降低。因此，BPS可能诱导线粒体依赖性凋亡途径。BPS还降低了BDNF、TrkB和p-CREB的水平，用7,8-DHF预处理可减轻其细胞毒性作用。因此，BPS诱导的细胞毒性可能由BDNF/TrkB/CREB信号通路介导。
