Role of adenosine A2A receptors in cytoprotection

我们已经证明，A2A腺苷受体的刺激诱导细胞死亡的减少。然而，这种有益作用的分子机制尚不清楚。我们假设这部分是由于研究这种受体的条件。值得注意的是，腺苷的浓度，这是一种与这种受体反应的天然物质，在特定条件下，如氧还原，会增加。很少有研究考虑到这一点。在本提案的第一部分中，我们决定研究在从正常到减少氧可用性的不同条件下该受体激活后观察到的细胞内变化。在本提案的第二步中，我们将进行研究，以确定该受体调节的哪些酶对保护称为凋亡的特定死亡细胞是重要的。在本课程结束时，我们应该对这种受体保护作用的分子机制有了更好的了解。

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.