trans,trans-2,4-Decadienal 通过损害线粒体功能和自噬通量诱导内皮细胞损伤,Food & Function

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trans,trans-2,4-Decadienal 通过损害线粒体功能和自噬通量诱导内皮细胞损伤
Food & Function ( IF 5.1 ) Pub Date : 2021-4-26 , DOI: 10.1039/d1fo00372k
Yuanyuan Hu ₁ , Guanhua Zhao ₁ , Lei Qin ₂ , Zhenlong Yu ₃ , Min Zhang ₁ , Xiaochi Ma ₃ , Dayong Zhou ₂ , Fereidoon Shahidi ₄ , Beiwei Zhu ₂

Affiliation

本研究调查了反式、反式-2,4-癸二烯醛 ( tt -DDE) 对血管内皮细胞的毒性作用以及所涉及的潜在机制。人脐血管内皮细胞(HUVECs)用不同浓度的tt -DDE处理24 h，测定细胞活力、集落形成能力、细胞凋亡、线粒体功能和自噬途径。结果表明，tt -DDE 剂量依赖性地抑制细胞活力和集落形成，并增加 HUVEC 中乳酸脱氢酶 (LDH) 的释放和凋亡。此外，tt-DDE 暴露诱导了广泛的线粒体损伤，如线粒体 DNA 拷贝数、ATP 合成和线粒体膜电位降低以及线粒体活性氧 (ROS) 产生和细胞色素c从线粒体释放增加所证明的。tt -DDE 还通过增加 DNM1L 蛋白表达和 DNM1L 线粒体易位诱导线粒体断裂和裂变。此外，tt -DDE 处理导致自噬流的阻塞和自噬体在内皮细胞中的积累。进一步的研究表明，3-甲基腺嘌呤对自噬的抑制加剧了tt -DDE 诱导的线粒体功能障碍和细胞损伤。然而，通过清除 ROSN-乙酰-L-半胱氨酸 (NAC) 显着防止了tt -DDE 诱导的线粒体损伤、自噬功能障碍和细胞损伤。这些数据表明tt -DDE 通过损害线粒体功能和自噬通量诱导内皮细胞损伤。

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trans,trans-2,4-Decadienal induces endothelial cell injury by impairing mitochondrial function and autophagic flux

This study investigated the toxic effects of trans,trans-2,4-decadienal (tt-DDE) on vascular endothelial cells as well as the underlying mechanisms involved. Human umbilical vascular endothelial cells (HUVECs) were treated with different concentrations of tt-DDE for 24 h, and cell viability, colony formation ability, apoptosis, mitochondrial function and autophagy pathway were determined. The results showed that tt-DDE dose-dependently inhibited cell viability and colony formation, and increased lactate dehydrogenase (LDH) release and apoptosis in HUVECs. Besides, tt-DDE exposure induced extensive mitochondrial damage, as evidenced by the decreased mitochondrial DNA copy number, ATP synthesis, and mitochondrial membrane potential, and increased mitochondrial reactive oxygen species (ROS) production and cytochrome c release from mitochondria. tt-DDE also induced mitochondrial fragmentation and fission by increasing DNM1L protein expression and DNM1L mitochondrial translocation. Additionally, tt-DDE treatment resulted in the blockage of autophagic flux and accumulation of autophagosomes in endothelial cells. Further investigation revealed that the inhibition of autophagy by 3-methyladenine aggravated tt-DDE-induced mitochondrial dysfunction and cell injury. However, scavenging of ROS by N-acetyl-L-cysteine (NAC) significantly prevented tt-DDE-induced mitochondrial damage, autophagy dysfunction, and cell injury. These data indicated that tt-DDE induced endothelial cell injury through impairing mitochondrial function and autophagic flux.

更新日期：2021-05-17

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