聚合酶三角相互作用蛋白2通过调节ROS介导的ZO-1酸化和在内皮间边界的局部化来调节大脑血管透性
Keke Wang1,2, Hongyan Qu1, Ruinan Hu1
1Department of Medicine, Division of Cardiology, Emory University School of Medicine, 1750 Haygood Dr NE, HSRB-II, Atlanta, GA, 30322, USA.
Cell communication and signaling : CCS
|January 8, 2025
概括
聚合酶三角相互作用蛋白2 (Poldip2) 通过通过线粒体反应性氧物种 (ROS) 促进ZO-1氨酸酸化,加剧了血脑屏障的破坏. 减少Poldip2或ROS可以减轻这种效应,为中风提供治疗点.
科学领域:
- 神经科学是一个神经科学.
- 血管生物学 血管生物学
- 细胞生物学 细胞生物学
背景情况:
- 聚合酶三角相互作用蛋白2 (Poldip2) 涉及中风后血脑屏障 (BBB) 的破坏.
- 波尔迪普2影响BBB完整性的确切机制,特别是它对内皮紧结 (TJ) 的影响,仍然不清楚.
研究的目的:
- 阐明Poldip2调解BBB干扰的机制.
- 研究Poldip2在TJ蛋白ZO-1的酸化和稳定中的作用.
主要方法:
- 使用内皮特异性的Poldip2淘汰赛小鼠和体外内皮细胞 (EC) 模型.
- 通过使用埃文斯蓝色染料扩散评估脑血管透性.
- 通过免疫光和免疫沉检查了ZO-1局部化和酸化.
主要成果:
- 波尔迪普2的删除消除了缺血引起的BBB透性,并抑制了TNF-α引起的EC透性.
- 过度表达Poldip2增加了EC的透性,破坏了ZO-1的局部化,并增强了活性氧物种 (ROS) 的产生.
- 聚二诱导的ZO-1氨酸酸化与线粒体ROS有关,并通过抗氧化剂减轻.
结论:
- 波尔迪普2通过一种依赖于线粒体ROS的机制促进了EC的透性.
- 波尔迪普2诱导ZO-1氨酸酸化,导致脑缺血后的BBB中断.
- 准Poldip2或ROS可能为与中风相关的BBB损伤提供治疗策略.
相关概念视频
Regulation of Angiogenesis and Blood Supply
2.5K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K
Cell Polarization by Rho Proteins
2.7K
Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
2.7K
Membrane Fluidity
10.9K
Membrane fluidity is explained by the fluid mosaic model of the cell membrane, which describes the plasma membrane structure as a mosaic of components—including phospholipids, cholesterol, proteins, and carbohydrates—that gives the membrane a fluid character.
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is...
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is...
10.9K


