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酸盐调节内皮线粒体功能和屏障完整性

Reham Atallah¹, Juergen Gindlhuber², Wolfgang Platzer¹

¹Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Division of Pharmacology, Medical University of Graz, 8010 Graz, Austria.

Antioxidants (Basel, Switzerland)

|January 8, 2025

概括

升高的酸盐会严重损害内皮细胞的线粒体功能和屏障完整性. 然而,随着时间的推移,细胞恢复,涉及VEGF和前列腺素通路,而 Askorbic 酸提供保护.

科学领域:

细胞生物学细胞生物学
生物化学生物化学
病理生理学病理生理学

背景情况:

内皮功能障碍与癌症和心血管疾病等病理状况有关.
在这些条件下观察到乱的TCA循环和酸盐积累.
苏酸在炎症中的作用已被认可,但其对内皮细胞的影响尚不清楚.

研究的目的:

研究细胞内糖酸盐的升高如何影响内皮细胞功能和表型.
探索内皮细胞中酸盐诱导的变化背后的机制.

主要方法:

在体外功能测试使用人类静脉内皮细胞 (HUVECs).
用二甲基糖酸盐 (DES) 进行刺激,这是一种细胞透的糖酸盐模拟物.
MTS测定,ROS测量,线粒体膜潜能评估,海马线粒体压力测试,西部抹杀,基因表达分析和内皮屏障透性测定.

主要成果:

在HUVEC中,DES急剧降低了代谢活性,增加了ROS,并降低了线粒体膜潜力.
DES降低了氧气消耗率,最大呼吸和ATP的产生.
DES诱导了急性内皮膜屏障的透性和改变了细胞形态,但细胞在一夜之间出现了发芽和屏障恢复的恢复.
酸盐诱导的变化包括过渡的ERK1/2酸化变化,混合的亡/生存基因表达特征,以及VEGF的上调.
屏障恢复是由COX-2/PGE2/EP4信号传递调节的,而 Askorbic 酸防止了急性屏障破坏.

结论:

酸盐显著调节内皮线粒体功能和屏障完整性.
内皮细胞表现出一个涉及VEGF和前列腺素生产的平衡反应.
亚斯科布酸可以防止急性苏酸诱导的内皮屏障破坏.

关键词:

屏障的完整性屏障的完整性内皮细胞是内皮细胞.线粒体功能线粒体功能有活性氧物种的反应性氧物种.顺酸是什么意思顺酸

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