人类有机离子载体4 (OAT4) 活性受到双相似物抑制
Hélène Le Mentec1, David Malnoë2, Marc Le Vée1
1Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail), UMR_S 1085, F-35000, Rennes, France.
Environmental pollution (Barking, Essex : 1987)
|December 17, 2025
概括
包括BPA替代品在内的环境双 (BP) 类似物抑制有机离子载体4 (OAT4). 对Pergafast® 201 (PF201) 的职业暴露可能导致人类的OAT4抑制.
科学领域:
- 毒理学 毒理学 毒理学
- 环境健康 环境健康
- 药理学 药理学是指药理学的学科.
背景情况:
- 有机离子运输体4 (OAT4) 对于在脏和胎盘中运输异生菌和内生化合物至关重要.
- 双 (BP) 类似物,包括双A (BPA) 的替代品,是广泛存在的环境污染物.
- 没有充分了解BP类似物和OAT4之间的潜在相互作用.
研究的目的:
- 调查环境BP类似物是否与OAT4功能相互作用和影响.
- 评估各种BP类似物对OAT4活性和基质运输的抑制潜力.
- 探索BP类似物对OAT4抑制的影响,特别是对于职业暴露.
主要方法:
- 使用OAT4过度表达的HEK-293细胞测量OAT4活性,使用6-碳氧化素.
- 评估了23种BP类似物对OAT4活性和雌激素-3-硫酸盐运输的影响.
- 进行了度依赖的抑制研究,对接模拟,以及体外到体外抽取.
主要成果:
- 7/23 BP类似物抑制了OAT4活性,其中Pergafast® 201 (PF201),四博乙烯A (TBBPA) 和四博乙烯A (TCBPA) 显示出显著的度依赖抑制 (IC50:0.95-1.48μM).
- 大多数测试的BP类似物通过OAT4减少了雌激素-3-硫酸盐的运输;PF201还抑制了OAT1和OAT3.3的运输体.
- 对接模拟表明PF201与OAT4的关键部位结合,并且在体外到体内外推断预测职业PF201暴露可能会抑制人类OAT4.
结论:
- OAT4是环境BP类似物,包括BPA替代品的分子标.
- 抗氧化类似物可以损害内源性化合物和药物的OAT4介导的运输.
- 职业接触PF201对人类造成OAT4抑制的风险.
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