Wang Yi, Shan Jing, Zhang Ling, Wang Rui, Wu Meng-Yu, Li Hong-Mei, Xu Hai-Ming
School of Public Health, Ningxia Medical University, Yinchuan, Ningxia 750004, China; The Key Laboratory of Environmental Factors and Chronic Disease Control of Ningxia, No. 1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China; Department of Experimental Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
School of Public Health, Ningxia Medical University, Yinchuan, Ningxia 750004, China; The Key Laboratory of Environmental Factors and Chronic Disease Control of Ningxia, No. 1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China; Xi'an GEM Flowers Changqing Hospital, Xi'an, Shanxi 710000, China.
Ecotoxicol Environ Saf. 2025 Jan 1;289:117445. doi: 10.1016/j.ecoenv.2024.117445. Epub 2024 Nov 30.
Tetrabromobisphenol A (TBBPA) is one of the brominated flame retardants (BFRs) widely used in industry, which has a broad toxic effect on organisms. However, there is still limited research on the neurotoxic mechanism of TBBPA. Using mouse hippocampal neurons (HT22) cells, the toxicity of TBBPA was evaluated, especially focusing on its alteration on the key molecules in FAM171A2-GRN-NF-κB signaling pathway. The results showed that TBBPA exposure could lead to an increase in the production of inflammation-related genes IL-6, iNOS, TGF-β1, COX2, and TNF-α in both HT22 cells and HT22-AD-model, intensifying the inflammatory response; it inhibits the mRNA expression of antioxidative enzymes genes Sod1, Cat, Gpx1, and Gsta1, resulting in reduced antioxidant enzyme activities of SOD, CAT, and GSH-Px/GPX. Mechanistically, TBBPA caused the upregulation of FAM171A2 expression level, alongside increased GRN, IκBα and p65 levels; whereas the expression of GRN, IκBα and p65 was decreased after FAM171A2 knockdown, demonstrating TBBPA-induced upregulation of FAM171A2 should be responsible for the increased GRN, IκBα and p65 expression. Therefore, for the first time, our data indicate that TBBPA-induced oxidative stress and inflammatory response is closely related to the FAM171A2-GRN-NF-κB pathway.
四溴双酚A（TBBPA）是工业上广泛使用的溴化阻燃剂（BFRs）之一，对生物体具有广泛的毒性作用。然而，关于TBBPA神经毒性机制的研究仍然有限。利用小鼠海马神经元（HT22）细胞评估了TBBPA的毒性，特别关注其对FAM171A2-GRN-NF-κB信号通路中关键分子的影响。结果表明，TBBPA暴露可导致HT22细胞和HT22-AD模型中炎症相关基因IL-6、iNOS、TGF-β1、COX2和TNF-α的产生增加，加剧炎症反应；它抑制抗氧化酶基因Sod1、Cat、Gpx1和Gsta1的mRNA表达，导致超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH-Px/GPX）的抗氧化酶活性降低。从机制上讲，TBBPA导致FAM171A2表达水平上调，同时GRN、IκBα和p65水平增加；而FAM171A2敲低后GRN、IκBα和p65的表达降低，表明TBBPA诱导的FAM171A2上调应负责GRN、IκBα和p65表达的增加。因此，我们的数据首次表明，TBBPA诱导的氧化应激和炎症反应与FAM171A2-GRN-NF-κB通路密切相关。
