持续内分泌干扰化学物质对人类核受体的影响:来自In Silico和实验性特征的见解
Harrish Ganesh1, James Moran2, Saptarshi Roy3
1VCU Life Sciences, Virginia Commonwealth University, Richmond, VA 22043, USA.
International journal of molecular sciences
|April 17, 2025
概括
持久性内分泌干扰化学物质 (EDC) 强烈地与人类核受体 (hNR) 结合,可能破坏新陈代谢并导致癌症. 在这项研究中,和多醇基物质 (PFAS) 显示出最高的结合亲和力.
科学领域:
- 环境化学环境化学
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
背景情况:
- 内分泌干扰化学物质 (EDC) 是与癌症有关的持续性环境污染物.
- 人类核受体 (hNR) 是EDC诱导的新陈代谢和内分泌功能障碍的关键目标.
- 有限的综合数据存在于EDC与各种hNRs的相互作用.
研究的目的:
- 描述持久EDC和关键hNR之间的相互作用.
- 调查EDC与hNRs的结合机制和亲和关系.
- 评估EDC-hNR相互作用对细胞通路的功能影响.
主要方法:
- 用分子对接模拟来分析EDC-hNR结合.
- 根据与疏水氨基酸的相互作用来评估结合亲和力.
- 实验室试验 (hNR活性和转录因子通路试验) 在HepG2细胞中进行.
主要成果:
- 持久性EDCs,包括PFAS,塑料添加剂,双,PBDE和酸盐,显示强烈结合hNRs (PXR,CAR,PPARs,AR,RORγt).
- 由于疏水性和极性相互作用,PFAS表现出最高的结合亲和力.
- 酸盐 (DCHP,DEHP) 对大多数测试的hNRs表现出agonistic作用,并且观察到VDRE和PXR的基因表达增加.
结论:
- 持久EDC有效地与hNR结合,主要是通过疏水性相互作用.
- PFAS显示出显著的结合亲和力,这表明可能存在广泛的内分泌干扰.
- 进一步的研究对于了解这些EDC所带来的长期内分泌干扰和致癌风险至关重要.
关键词:
NR激活检测试验NR激活检测试验NR转录因子激活试验试验NR转录因子激活试验在PFAS中,我们可以使用PFAS.基因调节 基因调节 基因调节人类核受体 (hNRs)疏水性相互作用 疏水性相互作用分子对接模拟分子对接模拟纳米塑料是一种纳米塑料.持续的内分泌干扰化学物质 (EDCs)甲酸 甲酸是一种更多相关视频
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