Role of adenosine A2A receptors in cytoprotection

我们已经证明，刺激A2A腺苷受体可以减少细胞死亡。然而，这种有益作用的分子机制却知之甚少。我们推测，这在一定程度上是由于研究这种受体的条件所致。值得注意的是，腺苷是与该受体反应的天然物质，在特定条件下，如氧气还原，其浓度会增加。很少有研究考虑到这一点。在本方案的第一部分，我们决定研究在不同条件下激活该受体后观察到的细胞内变化，从正常到氧可获得性不同。在该方案的第二步，我们将进行研究，以确定该受体调节的哪种酶(S)对保护特定的死亡细胞免受称为凋亡的影响是重要的。在本程序结束时，我们应该对该受体的保护作用所涉及的分子机制有更好的了解。

We have demonstrated that the stimulation of A2A adenosine receptors induced a reduction in cell death. However, the molecular mechanisms for this beneficial effect are poorly understood. We hypothesize that this is partly due to the conditions used to study this receptor. Notably, the concentration of adenosine, which is the natural substance reacting with this receptor, increases during specific conditions such as oxygen reduction. Few studies have taken this important point into consideration.In the first part of this proposal, we have decided to study the intracellular changes observed following the activation of this receptor in different conditions varying from normal to reduced oxygen availability.In the second step of this proposal, we will perform study to determine which enzyme(s) modulated by this receptor is/are important to protect from specific death cell called apoptosis.At the end of this program, we should have a better idea of the molecular mechanisms involved in the protective effect of this receptor.