PM2.5通过AHR-SIRT1-PGC-1α介导的线粒体损伤诱导心脏缺陷
Jin Chen1, Mingxuan Zhang1, Stanley Aniagu2
1Suzhou medical college, Soochow University, Suzhou, China; MOE Education Key Laboratory of Geriatric Diseases and Immunology, Suzhou, China.
Environmental toxicology and pharmacology
|February 17, 2024
概括
暴露于颗粒物 (PM2.5) 可能通过损害线粒体导致先天性心脏缺陷. 我们的研究表明,PM2.5触发了AHR/SIRT1/PGC-1α通路,导致心脏异常.
科学领域:
- 环境健康 环境健康
- 心血管生物学 心血管生物学
- 线粒体医学 线粒体医学
背景情况:
- 新出现的证据将细颗粒物 (PM2.5) 暴露与先天性心脏病联系起来.
- 连接PM2.5与心脏缺陷的潜在分子机制在很大程度上是未知的.
- 线粒体功能障碍越来越多地与各种发育障碍有关.
研究的目的:
- 调查阿里尔碳化合物受体 (AHR) 和PGC-1α在PM2.5引起的心脏缺陷中的作用.
- 阐明通过PM2.5可能导致心脏异常的信号通路.
- 探索针对线粒体通路的潜在治疗干预措施.
主要方法:
- 利用斑马鱼幼虫作为PM2.5 (可提取有机物 - EOM) 暴露的模型系统.
- 给药ZLN005,一个PGC-1α激活剂,以评估其保护作用.
- 分析了PGC-1α表达和活性,线粒体生物发生和功能,亡,SIRT1活性和NAD+/NADH比率.
- 研究了AHR在调节SIRT1和TiPARP表达中的作用.
主要成果:
- 在斑马鱼中,ZLN005治疗抵消了EOM诱导的心脏缺陷.
- EOM暴露导致PGC-1α下调,线粒体功能受损和亡增加.
- EOM通过SIRT1-依赖脱乙基化抑制了PGC-1α活性.
- 通过EOM激活AHR降低了SIRT1水平和NAD+/NADH比,同时增加了TiPARP转录.
结论:
- 暴露于PM2.5通过AHR/SIRT1/PGC-1α信号通路诱导线粒体损伤和先天性心脏缺陷.
- 针对AHR/SIRT1/PGC-1α轴可能提供一种策略,以减轻PM2.5相关的心血管风险.
- 这项研究为空气污染的心脏毒性提供了新的机制性见解.
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