线粒体混乱:香烟烟雾如何通过MMS19降解诱导胎盘功能障碍
Pei Zhou1, Feng Jin1, Shenshen Yao1
1Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, PR China.
Ecotoxicology and environmental safety
|January 17, 2025
概括
香烟烟雾通过破坏铁硫 (ISC) 蛋白质和CIA通路来损害胎盘发育,导致 trofhoblast 功能受损和潜在的不良妊娠结果.
科学领域:
- 生殖生物学 生殖生物学
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
背景情况:
- 吸烟会对胎盘生长和胚胎发育产生不利影响.
- 将CS暴露与胎盘功能障碍联系在一起的机制尚未完全理解.
研究的目的:
- 研究CS对 trofhoblast细胞增殖和调控细胞死亡 (RCD) 的影响.
- 检查CS干扰与铁硫 (ISC) 蛋白和细胞质ISC组合 (CIA) 途径.
主要方法:
- 鼠对被动吸烟和HTR-8/Sneo细胞对香烟烟雾提取物 (CSE) 的暴露.
- 对胎盘组织,ISC蛋白水平,CIA通路组件和细胞死亡标记物的分析.
- 分子对接,MMS19的基因淘汰 (KD),转录组分析和SMAD通路评估.
主要成果:
- CS暴露破坏了CIA途径,降低了ISC蛋白质的调节,并损害了老鼠胎盘中的ISC成熟.
- 通过损害CIA通路和ISC蛋白质,CSE抑制了热囊细胞的增殖,诱导了自和亡.
- 尼古丁和尼古提林促进MMS19的自降解,这是CIA的关键组成部分.
- MMS19 KD导致ISC蛋白的自降解,抑制增殖,诱导线粒体功能障碍,ROS积累和细胞死亡.
- 通过SMAD途径失调调节的介导MMS19 KD诱导的线粒体损伤.
- 吸烟者的胎盘组织显示ISC蛋白和SMAD通路受损.
结论:
- 由CS破坏CIA通路和ISC蛋白质的破坏有助于胎盘发育不良.
- 准MMS19-SMAD通路可能会减轻CS暴露的不良妊娠结果.
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