安格II通过转录因子调节NOX2活动来促进ET-1生产 Oct-1-1
Julian Kamhieh-Milz1, Lei Chen2,3, Claudia Goettsch4,5
1Institute of Transfusion Medicine (J.K.-M.), Charité Universitätsmedizin Berlin, Germany.
Arteriosclerosis, thrombosis, and vascular biology
|June 29, 2023
概括
ангиотензин II (Ang II) 通过NOX2衍生的超氧化物在内皮细胞中促进内末林-1 (ET-1) 的产生,特别是在有氧饮食期间. 这一途径涉及转录因子Oct-1,突出显示了血管反应中的关键机制.
科学领域:
- 心血管生物学 心血管生物学
- 氧化压力是一种氧化压力.
- 分子机制的分子机制
背景情况:
- 异质性饮食可以触发由尼古丁胺氨酸二核酸盐氧化酶 (NOX) 的超氧化离子介导的血管效应.
- ангиотензин II (Ang II) 与这些血管作用有关,但NOX异型,特别是NOX2在Ang II诱导的内甲蛋白-1 (ET-1) 生产中的确切作用仍未完全阐明.
研究的目的:
- 研究NOX2在人类微血管内皮细胞中促进Ang II诱导的ET-1产生的机制.
- 确定转录因子Oct-1和超氧化离子生产在该途径中的作用.
主要方法:
- 在野生型 (WT) 和Nox2-缺乏的小鼠中对高脂肪饮食影响的比较分析.
- 使用人类微血管内皮细胞进行体外研究,包括ELISA,RT-qPCR,电泳性移动性转移试验,促进体删除,RNA干扰和药理抑制.
- 使用光细胞标记的超氧化离子生产的可视化.
主要成果:
- 在WT小鼠中,高脂肪饮食增加了心脏Ang II和ET-1,但在Nox2缺乏的小鼠中没有.
- 格II刺激了内皮细胞中的ET-1生产,这取决于NOX2的表达.
- 通过Oct-1转录因子与NOX2促进体结合,Ang II对NOX2进行了上调,导致超氧化物产生增加.
- 抑制Oct-1或超氧化物 (使用SOD) 取消了Ang II诱导的ET-1生产.
结论:
- ангиотензин II (Ang II) 在动性条件下促进内皮内甲蛋白-1 (ET-1) 的产生.
- 这一过程是由NOX2衍生的超氧化离子介导的.
- 转录因子Oct-1在上调NOX2表达方面发挥着至关重要的作用,将Ang II与增加的氧化应激和ET-1生产联系起来.
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