Equilibrative Nucleoside Transporters ENT1 and ENT2 during Ischemia and Reperfusion Injury

缺血和再灌注损伤期间的平衡核苷转运蛋白 ENT1 和 ENT2

• 批准号: 46834344
• 负责人: Professor Dr. Peter Rosenberger
• 金额: --
• 依托单位: Klinik für Anaesthesiologie und Intensivmedizin
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/46834344?language=en
• 关键词: Equilibrative; Nucleoside; Transporters; ENT1; ENT2

Limited oxygen availability as occurs during ischemia and reperfusion injury represents an important aspect of critical illness. As central modulator of inflammatory responses, adenosine signaling activates endogenous pathways to balance inflammatory responses during limited oxygen availability. Once generated into the extracellular milieu, adenosine is rapidly cleared mainly through uptake via equilibrative nucleoside transporters (ENT1/2). Recent studies suggest that endothelial/epithelial nucleoside transporter gene expression is attenuated by hypoxia. In fact, we could show that repression of vascular adenosine uptake by hypoxia represents an innate adaptive pathway coordinated by hypoxia. Here, we propose to study dynamics of ENT1 and ENT2 during ischemia and reperfusion injury of the heart, the kidney and the intestine. It is our expectation that these studies will shed new light on molecular mechanisms of how ischemia and reperfusion injury modulates ENTdependent changes of adenosine signaling events and lay the groundwork for novel therapeutic approaches in the treatment of ischemia and reperfusion injury.

缺血和再灌注损伤期间发生的氧气供应有限是危重疾病的一个重要方面。作为炎症反应的中心调节剂，腺苷信号传导激活内源性途径，以在氧气供应有限的情况下平衡炎症反应。一旦进入细胞外环境，腺苷主要通过平衡核苷转运蛋白 (ENT1/2) 的摄取而被快速清除。最近的研究表明，内皮/上皮核苷转运蛋白基因表达因缺氧而减弱。事实上，我们可以证明缺氧对血管腺苷摄取的抑制代表了缺氧协调的先天适应性途径。在这里，我们建议研究 ENT1 和 ENT2 在心脏、肾脏和肠道缺血和再灌注损伤期间的动态。我们期望这些研究将为缺血和再灌注损伤如何调节腺苷信号事件的耳鼻喉科依赖性变化的分子机制提供新的线索，并为治疗缺血和再灌注损伤的新治疗方法奠定基础。