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NEAT1_2 和 DAZAP1, 抛光镜组件, 与 PXR 相互作用, 以负面调节 CYP3A4 诱导

Rei Mitamura¹, Masataka Nakano², Motoki Isono¹

¹Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences (R.M., Ma.N., M.I., K.K., T.F., Mi.N.) and WPI Nano Life Science Institute (WPI-NanoLSI) (Ma.N., K.K., T.F., Mi.N.), Kanazawa University, Kanazawa, Japan.

Drug metabolism and disposition: the biological fate of chemicals

|June 22, 2023

概括

含有NEAT1_2和DAZAP1的 Paraspeckles 捕获孕妇X受体 (PXR),以限制药物代谢. 激活PXR连接体释放PXR,增强CYP3A4的诱导.

科学领域:

细胞生物学细胞生物学
分子生物学分子生物学
药理学药理学是指药理学的学科.

背景情况:

人类孕妇X受体 (PXR) 是药物代谢酶的关键调节者,如CYP3A4.4.
PXR与DAZ关联蛋白1 (DAZAP1) 相互作用,这是一个帕拉斯佩克尔成分,这种相互作用被利芬素破坏.

研究的目的:

为了研究斑在PXR介导的转录调节中的作用.
为了阐明斑成分如何影响PXR活性和下游基因表达.

主要方法:

免疫沉试验用于识别PXR与斑成分的相互作用.
针对NEAT1_2和DAZAP1.1的淘汰实验.
路西法雷斯记者测定以评估PXR事务激活活动.

主要成果:

PXR与DAZAP1和NEAT1_2相互作用,这是一个长的非编码RNA.
利芬素是一种PXR配体,它将PXR与NEAT1_2.2.分离.
抑制NEAT1_2或DAZAP1显著增强了PXR介导的CYP3A4诱导.
抛光镜似乎封存了PXR,对其转录活动产生了负面调节.

结论:

抛光晶体成分NEAT1_2和DAZAP1对PXR诱导的CYP3A4表达进行负调节.
抛光镜可能充当PXR的储存器,调节其可用于转录激活的可用性.
这项研究揭示了一种新的机制,即虫通过PXR调节影响药物代谢.

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