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西格玛1R通过IRE1α/XBP1通路恢复线粒体能量代谢

Wei Yan^1,2, Tongyuan Deng¹, Da Huang¹

¹Department of Cardiovascular Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise City, Guangxi Province, China.

Scientific reports

|December 20, 2025

概括

西格玛1受体 (Sigma1R) 通过改善线粒体功能和调节,保护心脏细胞免受心房动损伤. 这表明Sigma1R是治疗AF的潜在治疗点.

科学领域:

心血管生物学心血管生物学
线粒体医学线粒体医学
细胞生理学细胞生理学

背景情况:

心房动 (AF) 涉及到心房肌细胞中线粒体能量代谢的显著重塑.
西格玛1受体 (Sigma1R) 在细胞应激反应中发挥作用,但其在AF相关的线粒体变化中的特定功能尚不清楚.

研究的目的:

调查Sigma1R在AF期间线粒体功能障碍中的作用.
阐明SIGMA1R效应背后的分子机制.
评估Sigma1R作为AF的潜在治疗点.

主要方法:

HL-1心房肌细胞被用来通过tachypacing来建模AF.
晶状病毒向量调节了Sigma1R和IRE1α的表达.
检测包括CCK-8,流细胞计,TMRE,MitoSOX Red,ATP检测和成像.
西方布洛特和FISH分析了蛋白质表达和局部化.

主要成果:

时速加速诱导的亡,降低了Sigma1R,线粒体功能障碍,减少了ATP,增加了ROS和增加了细胞质.
西格玛1R过度表达保护了肌细胞,提高了活力,减少了亡,恢复了ATP,并降低了ROS和细胞质.
西格玛1R使平衡正常化,并抑制了内分泌网膜-线粒体接触扩张.
西格玛1R抑制了IRE1α/XBP1通路,而IRE1α过度表达则抵消了西格玛1R的保护作用.

结论:

西格玛1R通过增强线粒体功能,减少氧化应激和调节平衡来保护心房肌细胞免受太基间隔诱导的损伤.
这些保护作用主要通过抑制IRE1α/XBP1通路进行介导.
西格玛1R代表了一种有前途的治疗点,用于缓解AF中的线粒体重塑.

关键词:

心房动是一种心房动.的恒温稳定的恒温稳定通过 IRE1α/XBP1 途径.线粒体中的线粒体.西格玛1受体是一个受体.

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