Equilibrative Nucleoside Transporters ENT1 and ENT2 during Ischemia and Reperfusion Injury

在缺血和再灌注损伤期间发生的有限的氧气可用性代表危重病的一个重要方面。作为炎症反应的中枢调节剂，腺苷信号传导激活内源性途径以在有限的氧可用性期间平衡炎症反应。一旦产生到细胞外环境中，腺苷主要通过平衡型核苷转运蛋白（ENT 1/2）的摄取而迅速清除。最近的研究表明，内皮细胞/上皮细胞核苷转运蛋白基因表达减弱缺氧。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ENT 1和ENT 2在缺血和再灌注损伤的心脏，肾脏和肠道的动力学。我们期望这些研究将为缺血再灌注损伤如何调节腺苷信号事件的ENT依赖性变化的分子机制提供新的线索，并为缺血再灌注损伤的新治疗方法奠定基础。

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.