食品级TiO2/TDCPP同时暴露破坏了ACOD1/伊塔康酸轴,与微质中TET2-NF-κB炎症有关,恶化神经毒性
Qing Guo1, Duijuan Wang1, Changning Zhao1
1Center for Environment and Health in Water Source Area of South-to-North Water Diversion, School of Public Health, Hubei University of Medicine, Shiyan 442000, China; Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan 442000, China.
概括
食品级二氧化 (TiO2) 和TDCPP暴露会损害儿童的神经发育. 联合暴露激活了微质,导致神经元亡和炎症,表明伊塔科纳酸作为一种潜在的治疗方法.
科学领域:
- 环境毒理学环境毒理学
- 神经科学是一个神经科学.
- 分子生物学分子生物学
背景情况:
- 食品级二氧化 (TiO2) 和三 (1,3-二-2-) 酸盐 (TDCPP) 是常见的环境污染物.
- 儿童高暴露率引发了人们对神经发育风险的担忧.
- 同时暴露于TiO2和TDCPP的神经毒性影响尚不清楚.
研究的目的:
- 调查食品级TiO2和TDCPP的同时暴露的神经毒性.
- 阐明底层的细胞和分子机制.
- 探索潜在的治疗干预措施.
主要方法:
- 使用了C8-D1A星体细胞,BV2微质细胞和Neuro-2a神经母细胞瘤细胞系.
- 进行了毒性测定,共同培养实验,转录基因分析和RT-qPCR.
- 通过基因淘汰,外源性伊塔科纳酸干预和表观遗传学分析验证的发现.
主要成果:
- 结合TiO2和TDCPP暴露在BV2微质中显示出显著的毒性.
- 同时暴露导致Neuro-2a神经元间接通过微质激活引起的亡.
- 在BV2细胞中观察到Acod1/itaconate轴的下调,炎症性细胞因子和Tet2的上调以及NF-κB的激活.
- 这些分子变化与微质炎症和神经元亡相关.
结论:
- 同时暴露于食品级TiO2和TDCPP通过微质激活和炎症反应产生神经毒性.
- 涉及Tet2和NF-κB激活的表观遗传机制在观察到的神经毒性中起作用.
- 抑制了Acod1/itaconate通路,突出了其作为治疗点的潜力.
- 伊塔科纳酸可能具有缓解这些污染物引起的神经炎症的治疗潜力.
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