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在基因表达调节的关键因素的核细胞质局部的压力诱导的变化
Ali Khamit1, Payal Chakraborty1, Szabolcs Zahorán1
1Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of Szeged, H-6701 Szeged, Hungary.
International journal of molecular sciences
|April 13, 2024
概括
母亲吸烟会对新生儿的带血管产生毒性影响,诱导转录和DNA损伤反应中的分子适应. 这些变化突显了细胞应激和潜在的损伤,影响了婴儿的健康.
科学领域:
- 产周毒理学 产周毒理学
- 分子生物学分子生物学
- 健康和疾病的发育起源.
背景情况:
- 胎盘不能完全过有害物质,使胎儿暴露在母亲的环境毒素中.
- 母亲吸烟是产前暴露于有毒化合物的重要来源.
- 新生儿带血管是评估胎儿暴露和反应的直接接口.
研究的目的:
- 研究母亲吸烟对新生儿带 (UC) 血管的毒性影响.
- 分析UC血管内转录和转化过程中的压力诱导的适应.
- 检查mRNA凝聚物形成,转录调节和DNA损伤反应途径的变化.
主要方法:
- 来自吸烟 (Sm) 和不吸烟 (Ctr) 母亲产生的新生儿的UC血管的比较.
- 免疫光染色和共聚焦显微镜用于评估蛋白质局部化 (CNOT1, RPB1).
- 对DNA损伤反应标记物的评估,包括Poly ((ADP-ribose) 聚合酶-1.
主要成果:
- 在SmUC容器中观察到CNOT1颗粒的溶解,可能会增强转录和翻译.
- 在对照容器和Sm容器中,RNA聚合酶II酶 (RPB1) 的主导细胞质局部化.
- 在Sm样本中显著的内皮细胞损伤,由高的Poly ((ADP-ribose) 聚合酶-1水平证明.
- 对照容器的ex vivo金属暴露模仿了Sm样本的变化,证实了毒性反应中的标记物作用.
结论:
- 母亲吸烟诱导新生儿UC血管中的特定分子适应,影响关键的细胞过程.
- 观察到的适应包括mRNA凝聚力学,转录调节和DNA损伤反应.
- 这些发现强调了产前有毒物质暴露的有害影响,并提出了干预的目标.
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