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定量蛋白质组分析揭示了Nrf2在人类内皮细胞中的调节作用

Karan Naresh Amin¹, Palanichamy Rajaguru², Takayoshi Suzuki³

¹Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, 603203, Tamil Nadu, India.

Cell stress & chaperones

|July 24, 2023

概括

核因子红色素2相关因子2 (Nrf2) 调节细胞对压力的反应. 这项研究揭示了Nrf2通过影响关键细胞过程来维持内皮完整性的关键作用,为新疗法铺平了道路.

科学领域:

细胞信号传输和分子生物学
内皮细胞的功能和功能障碍.
蛋白质组学和生物信息学

背景情况:

核因子红色素2相关因子2 (Nrf2) 是细胞对氧化和内质网膜 (ER) 应激反应的关键调节者.
Nrf2通路的激活改善了内皮功能,但其确切的机制尚不清楚.
了解Nrf2的分子标对于开发治疗内皮功能障碍至关重要.

研究的目的:

阐明Nrf2影响内皮细胞功能的分子机制.
为了确定人类内皮细胞中Nrf2的新型蛋白相互作用体和下游点.
探索Nrf2在调节内皮质健康相关的关键细胞过程中的作用.

主要方法:

使用CRISPR/Cas9基因编辑,创建了Nrf2被淘汰的人体内皮细胞.
在这些细胞上使用液体染色学-质谱/质谱 (LC-MS/MS) 进行了蛋白质组分析.
对差异调节蛋白质的生物信息查使用Nrf2ome数据库进行.

主要成果:

总共有723种独特的蛋白质被确定,其中361种被发现在Nrf2被淘汰的细胞中受到差异调节.
确定了一个高度互联的信号网络,涉及70个直接的Nrf2反应器.
这些Nrf2调节的蛋白质参与了actin细胞骨调节,ER压力,血管生成,炎症,Hippo信号和EGF/FGF信号通路.

结论:

Nrf2在维持内皮完整性方面发挥着重要作用.
Nrf2 影响关键的细胞和代谢过程,包括细胞骨动态,应激反应和信号通路.
这些发现为针对Nrf2通路的新疗法提供了基础,以对抗内皮功能障碍.

关键词:

内皮细胞是内皮细胞.内皮质功能障碍内皮质功能障碍在 Nrf2ome 中,核因子红色素2相关因子核因子

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