失调的RBM24酸化损害了APOE翻译的基础心理压力诱导的心血管疾病
He Yang1, Lei Sun1, Xuemei Bai2
1College of Biomedicine and Health, College of Life science and Technology, Huazhong Agricultural University, Wuhan, 430070, China.
Nature communications
|November 23, 2024
概括
心理压力触发RBM24酸化,促进阿波利波蛋白E (APOE) 翻译,导致心血管疾病 (CVD). 这种分子联系解释了压力诱导的心脏事件,并为慢性压力提供了潜在的生物标志物.
科学领域:
- 分子生物学分子生物学
- 心脏病学 心脏病学
- 压力生理学 压力生理学
背景情况:
- 心理压力是心血管疾病 (CVD) 和心脏突然死亡的已知危险因素.
- 将压力与心血管疾病联系在一起的精确分子机制在很大程度上是未知的.
- RNA结合蛋白RBM24对于心脏功能和应激反应至关重要.
研究的目的:
- 阐明将心理压力与心血管疾病联系起来的分子途径.
- 调查RBM24酸化在压力诱导的心脏病理学中的作用.
- 确定与压力相关的CVD的潜在治疗目标和诊断标记.
主要方法:
- 使用了一种具有RBM24 (Rbm24 S181A KI) 特定突变的小鼠模型.
- 研究的信号通路包括eIF4E2-GSK3β和RBM24 S181酸化.
- 评估心脏功能,电生理学,脂质概况,肌肉强度和行为.
- 分析了阿波利波蛋白E (APOE) 翻译及其对心脏健康的影响.
- 研究RBM24-S181酸化作为人类受试者的血清标记物.
主要成果:
- 心理压力通过eIF4E2-GSK3β信号激活RBM24 S181酸化,促进APOE翻译.
- 在KI模型中,RBM24 S181酸化受损导致心脏功能障碍,心房动,血脂不良以及在压力下突然死亡.
- 心肌细胞中的APOE表达通过减轻ROS和线粒体功能障碍来挽救压力诱导的心脏异常.
- RBM24-S181酸化作为人体慢性压力的血清生物标志物.
结论:
- RBM24 S181酸化是关键的调解者,将心理压力与心血管疾病的病原体联系起来.
- 由RBM24酸化调节的eIF4E-APOE转化通路是压力诱导的心脏损伤的一个关键机制.
- 化RBM24-S181是一种新的诊断标志物,也是心理压力相关心血管疾病的潜在治疗点.
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