通过直接准PKM2来重编程新陈代谢,MC-LR在母胎界面触发了 trofhoblast 铁亡
Meihong Guo1, Xinrui Li2, Jingwen Zhang2
1Department of Clinical Nutrition, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; State Key Laboratory of Analytical Chemistry for Life Science, Division of Anatomy and Histo-embryology, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093, China.
Ecotoxicology and environmental safety
|November 22, 2025
概括
微囊素-氨酸-氨酸 (MC-LR) 暴露会通过改变PKM2功能引起胎盘铁,影响妊娠健康. 维生素B6的干预表明,它有望扭转这些有害影响.
科学领域:
- 环境毒理学环境毒理学
- 生殖生物学 生殖生物学
- 细胞病理学 细胞病理学
背景情况:
- 微cystin-leucine arginine (MC-LR) 与胎盘衍生的疾病,如孕前 (PE) 和胎儿生长限制 (FGR) 有关.
- 升高的胎盘MC-LR与PE和FGR患者的铁症严重程度相关.
研究的目的:
- 研究MC-LR诱导胎盘铁亡的机制.
- 为了确定参与MC-LR诱导的胎盘损伤的关键分子点.
主要方法:
- 使用了暴露于MC-LR的怀孕小鼠的胎盘样本和体外HTR-8/SVneo热原体细胞模型.
- 评估铁亡标志物,包括Fe2+积累,活性氧物种 (ROS) 和线粒体功能障碍.
- 研究了MC-LR与PKM2之间的相互作用,以及其对NRF2及其与铁死相关的基因的下游影响.
主要成果:
- MC-LR显著诱导了胎盘组织和 trofhoblast 细胞中的铁亡.
- MC-LR与PKM2结合,抑制其二聚体的形成,并损害其NRF2的联合激活器功能,导致GPX4和GCLC转录的减少.
- 增加的PKM2四聚体活性促进了糖解,增加了细胞对这种途径的依赖.
- 素 (维生素B6) 的干预成功地恢复了PKM2功能,并逆转了铁亡.
结论:
- 通过涉及PKM2.2.的双重调节机制,MC-LR触发了胎盘铁亡.
- PKM2的功能受到MC-LR的失调,影响NRF2信号传递和细胞代谢.
- 这项研究强调PKM2是缓解MC-LR诱导的胎盘损伤的关键目标,并提供了对怀孕环境风险的见解.
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