双 C 诱导心脏发育缺陷 通过 破坏 m6 A 恒温
Kunhui Su1,2, Jinfeng Liu1,2, Jiafeng Chen1,2
1The Fourth Affiliated Hospital, Department of Environmental Medicine, Zhejiang University School of Medicine, Zhejiang 310058, China.
Environmental science & technology
|August 29, 2024
概括
斑马鱼的双S (BPS) 暴露在婴儿中发现的水平导致心脏缺陷. BPS通过降低Mettl3的调节来破坏m6ARNA的修饰,影响心脏发育途径.
科学领域:
- 环境毒理学环境毒理学
- 发展生物学 发展生物学
- 分子表观遗传学 分子表观遗传学
背景情况:
- 由于监管禁令,双甲 (BPA) 替代品的使用越来越多.
- 这些替代品的发育毒性需要彻底调查.
研究的目的:
- 评估BPA替代品,特别是双S (BPS) 的发育毒性.
- 阐明BPS引起的心脏缺陷背后的分子机制.
主要方法:
- 斑马鱼模型暴露于不同度的BPS (41-150 nM).
- 对m6A稳态,Mettl3表达和Igf2bp2b结合目标mRNA的分析.
- 评估Acox1和Tnnt2d的mRNA和蛋白质水平.
- 对心脏形态和功能的评估.
主要成果:
- 在斑马鱼胚胎中,BPS暴露诱导了显著的心脏缺陷.
- BPS暴露下调了Mettl3,破坏了m6A的修改.
- 这种干扰损害了Igf2bp2b对m6A修饰的acox1和tnnt2dmRNAs的识别.
- 对Acox1和Tnnt2d的下调有助于心脏功能障碍.
结论:
- 内部暴露水平的BPS可以诱导心脏发育缺陷.
- 由BPS介导的心脏缺陷与Mettl3-m6A-Igf2bp2b通路的破坏有关.
- 这一途径影响心脏脂肪酸代谢和肌肉收缩,为BPS暴露提供了潜在的生物标志物.
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