Equilibrative Nucleoside Transporters ENT1 and ENT2 during Ischemia and Reperfusion Injury

在缺血和再灌流损伤中，有限的氧气供应是危重疾病的一个重要方面。作为炎症反应的中枢调节剂，腺苷信号通路激活内源性途径，在有限的氧气供应条件下平衡炎症反应。一旦产生到细胞外环境，腺苷主要通过平衡的核苷转运体(ENT1/2)被摄取而迅速清除。最近的研究表明，内皮/上皮核苷转运蛋白基因的表达因缺氧而减弱。事实上，我们可以证明，低氧抑制血管腺苷摄取是一种与低氧协调的先天适应性途径。在此，我们拟研究ENT1和ENT2在心脏、肾脏和肠缺血再灌注损伤过程中的动态变化。我们期望这些研究将有助于阐明缺血和再灌注损伤如何调节ENT依赖性腺苷信号转导事件的分子机制，并为治疗缺血和再灌注损伤的新的治疗方法奠定基础。

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.