在Secosterol-B介导的内皮功能障碍中,S-化有助于ER压力和侵略性形成
Maria Gemma Nasoni1, Erik Bargagni1, Francesca Monittola1
1Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.
Journal of lipid research
|March 11, 2026
概括
塞科斯特醇-B诱导内皮细胞中的化应激和蛋白质S-化,导致内质网膜应激和功能障碍. 这突出了氧化的含量.
科学领域:
- 血管生物学 血管生物学
- 内皮细胞生物学 内皮细胞生物学
- 氧化压力研究研究 氧化压力研究
背景情况:
- 细胞内膜网膜 (ER) 的压力与动脉样硬化有关,但机制尚不清楚.
- 氧化 (NO) 的波动和化应激 (NSS) 影响ER蛋白折叠.
- 蛋白质S-化 (SNO) 通过ER压力传感器影响神经元功能.
研究的目的:
- 研究secosterol-B在诱导ER压力和血管内皮中蛋白质S-化中的作用.
- 为了阐明连接secosterol-B,NSS和ER功能障碍在动脉样硬化中的机制.
主要方法:
- 使用的人类静脉内皮细胞 (HUVECs) 暴露于secosterol-B.
- 评估了IRE/XBP-1信号通路的激活.
- 测量了NO度,iNOS表达和蛋白质S-化 (包括PDI和GRP78).
- 评估ER胀和侵略性形成,有或没有L-NAME预处理.
主要成果:
- 在HUVEC中,Secosterol-B诱导了NSS和蛋白质S-化,激活了IRE/XBP-1通路.
- 观察到ER膜扩张,错误折叠的蛋白质积累,以及增加的NO/iNOS.
- 在PDI和GRP78.8的S-化中表现出改变.
- L-NAME 预治疗显著降低了 ER 胀和侵略性形成.
结论:
- 氧化和蛋白质S-化是secosterol-B诱导的ER功能障碍的关键调解者.
- 这些发现为动脉样硬化的血管功能障碍提供了新的见解.
- 确定了维护内皮质完整性的潜在治疗点.
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