Regulation and function of AMPK in endothelial cells

内皮细胞中 AMPK 的调节和功能

• 批准号: 115424795
• 负责人: Professorin Dr. Regine Heller
• 金额: --
• 依托单位: Institut für Molekulare Zellbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/115424795?language=en
• 关键词: Regulation; function; AMPK; endothelial; cells

The AMP-activated protein kinase (AMPK) plays a role in endothelial cell energy supply, stress protection and maintaining an antiinflammatory and antiatherogenic phenotype. The present project on AMPK regulation and function in endothelial cells will focus on two goals. We will prove the hypothesis that AMPK contains an inhibitory phosphorylation site and that targeting this site may be an approach to affect AMPK activity. We will further investigate whether and how AMPK is involved in the regulation of endothelial barrier function and how it controls endothelial cell migration. We hypothesize that AMPK activated at low energy state will preserve endothelial structure and junctions. In contrast, AMPK activated via receptor-dependent signalling pathways may support barrier disruption and cell movement. To verify this hypothesis, we will investigate the role of different pathways of AMPK stimulation, characterize AMPK targets related to the regulation of endothelial structure and perform functional assays in vitro and in mice with genetically ablated AMPK a1 subunit (permeability, migration, angiogenesis). We expect that the data obtained in this project will contribute to the development of pharmacological strategies targeting endothelial dysfunction.

AMP活化蛋白激酶（AMPK）在内皮细胞能量供应、应激保护以及维持血管内皮细胞和抗动脉粥样硬化表型中起作用。目前关于内皮细胞中AMPK调节和功能的项目将集中在两个目标上。我们将证明AMPK含有抑制性磷酸化位点的假设，靶向该位点可能是影响AMPK活性的一种方法。我们将进一步研究AMPK是否以及如何参与内皮屏障功能的调节以及它如何控制内皮细胞迁移。我们假设AMPK在低能状态下激活将保护内皮结构和连接。相反，通过受体依赖性信号通路激活的AMPK可能支持屏障破坏和细胞运动。为了验证这一假设，我们将研究AMPK刺激的不同途径的作用，表征与内皮结构调节相关的AMPK靶点，并在体外和基因消融AMPK α 1亚基（渗透性，迁移，血管生成）的小鼠中进行功能测定。我们期望本项目获得的数据将有助于开发针对内皮功能障碍的药理学策略。