Nrf2-mediated protective effect of alpha-lipoic acid on synaptic oxidative damage and inhibition of PKC/ERK/CREB pathway in bisphenol A-exposed HT-22 cells

作者全名："Wu, Dan; Sun, Qi; Wei, Wei; Bai, Yinglong; Zhai, Lingling; Jia, Lihong"

作者地址："[Wu, Dan] Chongqing Med Univ, Sch Publ Hlth, Dept Child & Adolescent Hlth, Chongqing 400016, Peoples R China; [Sun, Qi; Wei, Wei; Bai, Yinglong; Zhai, Lingling; Jia, Lihong] China Med Univ, Sch Publ Hlth, Dept Child & Adolescent Hlth, Shenyang 110122, Liaoning, Peoples R China; [Jia, Lihong] China Med Univ, Key Lab Environm Stress & Chron Dis Control & Prev, Minist Educ, Shenyang 110122, Liaoning, Peoples R China"

通信作者："Jia, LH (通讯作者)，China Med Univ, Sch Publ Hlth, Dept Child & Adolescent Hlth, Shenyang 110122, Liaoning, Peoples R China."

来源：FOOD AND CHEMICAL TOXICOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001096974200001

JCR分区：Q1

影响因子：3.9

年份：2023

卷号：181

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Bisphenol a; Alpha-lipoic acid; HT-22 cell; Oxidative stress; Synapse; Nrf2

摘要："The harmful effects of bisphenol A (BPA) on learning and memory may involve hippocampal oxidative damage; however, the underlying mechanism remains unclear. Antioxidants that antagonize BPA-induced neuronal oxidative damage lack research. This study aimed to develop an in vitro model using the HT-22 mouse hippo-campal neuronal cell line to investigate the neurotoxic mechanism of BPA and the protective effect of alpha-lipoic acid (ALA) on nuclear factor erythroid 2-related factor 2 (Nrf2) inhibition. The results showed that ALA reduced BPA-induced reactive oxygen species and neuronal nitric oxide synthase (nNOS) levels; however, inhibiting Nrf2 weakened the protective effects of ALA. BPA reduced mitochondrial complex I/III activity and ATP levels, but ALA ameliorated this damage. ALA improved the BPA-induced downregulation of the kelch-like ECH-associated protein 1 (keap1)/Nrf2 system, synaptic-related proteins, and the protein kinase C (PKC)/ extracellular signal-regulated kinase (ERK)/cAMP response element binding protein (CREB) pathway; however, the protective effects of ALA were weakened when Nrf2 was inhibited. Our results suggest that BPA causes oxidative damage to HT-22 cells by damaging mitochondrial function, nNOS, and the keap1/Nrf2 system, thereby impairing synaptic-related proteins and the PKC/ERK/CREB pathway. ALA counters BPA-induced damage via Nrf2, which may be a significant target for the protective action of ALA."

基金机构："National Natural Science Foundation of China [82073575, 81673190]"

基金资助正文：This research was supported by National Natural Science Foundation of China (grant number: 82073575 and 81673190) .