Equilibrative Nucleoside Transporters ENT1 and ENT2 during Ischemia and Reperfusion Injury

• Applicant: Professor Dr. Peter Rosenberger
• Subject Area: Anaesthesiology
• Term: from 2008 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 46834344

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.

• DFG Programme: Research Grants