通过RAGE轴在自主神经元中的高血糖引起的线粒体异常
María G Otero1, Nicolas Henao-Romero2, Trevor M Krysak2
1Board of Governors Regenerative Medicine Institute, Cedars Sinai Medical Center, Los Angeles, CA, 90048, US.
Scientific reports
|July 12, 2025
概括
糖尿病外围神经病变涉及线粒体功能障碍. 这项研究表明,高级糖化最终产品 (RAGE) 的受体在高血糖症期间调解自主神经元中的线粒体损伤.
科学领域:
- 神经科学是一个神经科学.
- 线粒体生物学 线粒体生物学
- 糖尿病学 糖尿病学
背景情况:
- 糖尿病外围神经病变的标志是线粒体功能障碍,包括呼吸障碍和活性氧物种 (ROS) 的增加.
- 糖尿病的高血糖会增加ROS,并促进先进的糖化最终产品 (AGE) 的形成,这与通过AGE (RAGE) 受体的自主功能障碍有关.
- RAGE在介导外周神经元中高血糖引起的线粒体异常中的作用尚不清楚.
研究的目的:
- 调查RAGE是否对于在高血糖条件下诱导自主神经元中的线粒体功能障碍至关重要.
- 在糖尿病神经病变的背景下阐明RAGE在线粒体形态,动力学和ATP生产中的作用.
主要方法:
- 检查了上性 (SCG) 中的线粒体形态,来自链毒素 (STZ) 诱导的糖尿病野生型 (WT) 和RAGE淘汰 (KO) 小鼠.
- 从暴露于高葡萄糖的WT和RAGE KO小鼠培养的SCG神经元中评估线粒体动力学和ATP生产.
- 利用RAGE抑制剂 (FPS-ZM1) 并分析了线粒体部分内的RAGE局部化.
主要成果:
- 患有糖尿病的WT小鼠在SCG中表现出胀的线粒体增加,SCG中晶状体受损,RAGE KO小鼠没有.
- 高葡萄糖诱导了WT SCG神经元中的线粒体碎片化和改变的轴突运输,但不是RAGE KO神经元.
- 与WT神经元相比,RAGE KO神经元在所有条件下都显示出明显较低的ATP产量.
- 在线粒体部分中检测到RAGE,并与神经元中的线粒体标记物结合.
结论:
- 先进糖化最终产品 (RAGE) 的受体在暴露于高血糖症的自主神经元内调解线粒体损伤方面发挥着关键作用.
- RAGE信号与糖尿病外围神经病变中观察到的形态和功能性线粒体损伤有关.
- 向RAGE可能为减轻糖尿病自主神经病变中的线粒体功能障碍提供治疗策略.
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