暴露于二--2-乙烯基) - 甲酸盐会通过降低蛋白质表达和ATP水平而损害胎盘P-糖蛋白排泄功能
Changing Tang1, Kunpeng Ren2, Miao Hou1
1Department of Cardiology, Children's Hospital of Soochow University, Suzhou, China.
2-乙基) 酸盐 (DEHP) 通过降低胎盘P-糖蛋白 (P-gp) 功能来降低胎儿保护. 这通过减少P-gp表达和关键ATP耗尽而发生,从而损害了对环境毒素的胎盘屏障.
科学领域:
- 环境健康 环境健康
- 毒理学 毒理学 毒理学
- 生殖生物学 生殖生物学
背景情况:
- 2-乙基) 酸盐 (DEHP) 是一种常见的增塑剂,与不良妊娠结果有关.
- 胎盘的P-葡萄糖蛋白 (P-gp) 载体对于保护胎儿免受异生菌的侵害至关重要.
- 通过DEHP影响胎盘P-gp功能的机制尚不清楚.
研究的目的:
- 为了调查DEHP是否会损害胎盘P-gp功能.
- 探索ATP枯竭在DEHP引起的P-gp功能障碍中的潜在作用.
- 阐明DEHP对胎盘传输的影响的潜在机制.
主要方法:
- 在DEHP暴露研究中使用了小鼠模型和Bewo细胞系.
- 评估的P-gp表达 (Abcb1b异型和总蛋白质) 和ATP水平.
- 使用罗达胺123和素进行功能测试,以测量P-gp流量.
- 研究了线粒体功能,NAD+/NADH比率和乳酸盐的产生.
主要成果:
- 暴露在DEHP下调了胎盘P-gp表达,并降低了胎盘组织和细胞中的ATP水平.
- 通过增加细胞内基质积累来证明受损的P-gp流动活性.
- 补充MgATP恢复了ATP水平,并挽救了P-gp功能.
- DEHP诱导了线粒体损伤和代谢转向糖解.
结论:
- 通过降低P-gp蛋白和ATP耗尽的调节,DEHP会损害胎盘P-gp功能.
- ATP耗尽是DEHP诱导的P-gp功能障碍的一个关键机制.
- 这些发现强调了DEHP通过代谢干扰来破坏胎儿保护机制的潜力.
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