核因子kappa B (NF-κB) 参与诱导的miR29a/b1的下调
Linping Wang1, Jingqi Zhang1, Yue Zhao1
1Department of Occupational Health, School of Public Health, Shanxi Medical University, China; Key Lab of Environmental Hazard and Health of Shanxi Province, Shanxi Medical University, China; NHC Key Laboratory of Pneumoconiosis (Shanxi), Medical University, Taiyuan, 030001 Shanxi Province, China.
概括
暴露会增加核因子-卡帕B (NF-κB),该核因子可以抑制微RNA-29a/b1 (miR29a/b1). 这导致β-分泌酶1 (BACE1) 和β-粉样蛋白 (Aβ) 斑块的增加,有助于阿尔茨海默病的发病.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 毒理学 毒理学 毒理学
背景情况:
- (Al) 是一种环境风险因素,与阿尔茨海默氏症 (AD) 病原发生有关.
- 暴露于Al会提高β-分泌酶1 (BACE1) 和粉样β (Aβ) 的水平.
- 之前的研究表明microRNA-29a/b1 (miR29a/b1) 对BACE1有负面调节,但核因子-kappa B (NF-κB) 的上游调节尚不清楚.
研究的目的:
- 为了阐明NF-κB和miR29a/b1.1.之间的关系.
- 为了确定参与NF-κB调节miR29a/b1的信号通路,在Al暴露的背景下.
主要方法:
- 通过在老鼠体内注射-马尔托拉酸 (Al(mal) 3) 来确定暴露的动物模型.
- 用NF-κB抑制剂给上腺染细胞瘤 (PC12) 细胞,这些细胞暴露于Al(mal) .
主要成果:
- 在大鼠的大脑Al积累和NF-κB水平之间观察到正相关性,与miR29a/b1水平相反相关.
- 抑制NF-κB显著上调了miR29a/b1的表达.
- 抑制NF-κB影响了BACE1mRNA和下游蛋白质的表达.
结论:
- 阿尔诱导的NF-κB作为miR29a/b1表达的负调节剂.
- 这种调节途径导致BACE1的增强表达,并促进Aβ斑块的形成.
- 这些发现突出了一个新的机制,通过NF-κB/miR29a/b1/BACE1轴将环境Al暴露与AD病理联系起来.
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