孕前X受体诱导的高胆固醇血清症的不良结局途径
Anna Itkonen1, Jukka Hakkola2, Jaana Rysä3
1School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland.
Archives of toxicology
|August 29, 2023
概括
激活孕前X受体 (PXR) 的化学物质可以导致高胆固醇血症,这是动脉样硬化的一个危险因素. 我们开发了一个不良结果途径 (AOP),详细介绍了将PXR激活与这种情况联系起来的分子机制.
科学领域:
- 毒理学和药理学 毒理学和药理学
- 分子生物学分子生物学
- 环境健康 环境健康
背景情况:
- 高胆固醇血症是动脉样硬化和全球健康负担的重要风险因素,可由药物和环境污染物引起.
- 孕妇X受体 (PXR) 是一个参与排毒的核受体,但它的激活越来越多地与代谢中断有关,包括高胆固醇血症.
研究的目的:
- 构建一个不良结果途径 (AOP),详细说明PXR激活导致高胆固醇血症的分子机制.
- 系统化关于PXR介导高胆固醇血症的知识,以改善化学风险评估.
主要方法:
- 文献审查和知识综合,以建立关键事件和关系.
- 构建一个线性AOP框架,将分子启动事件 (MIE) 与不利结果 (AO) 联系起来.
主要成果:
- PXR激活作为所描述的不良结果途径的分子启动事件 (MIE).
- 高胆固醇血症被确定为不良结果 (AO),通过PXR调节胆固醇合成和固醇调节元素结合蛋白2 (SREBP-2) 途径来调节.
结论:
- PXR激活代表了一种新的毒性途径,有助于高胆固醇血症.
- 开发的AOP为理解和评估与PXR激活化学品相关的风险提供了一个机制框架.
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