OPIOIDS AND CELLULAR SURVIVAL

本项目研究了Delta阿片肽DADLE和DADLE相关蛋白HIT(冬眠诱导触发)在组织存活中的生理效应和潜在的生化机制。在本财政年度，我们发现DADLE和HIT在小鼠输精管生物测定中显示出相似的生物活性。此外，我们已经在HIT中对一个类似α-1-糖蛋白的88 kDa冬眠相关蛋白进行了部分测序，这可能被证明是血液传播的HIT分子。德尔塔阿片肽DADLE也被发现可以逆转甲基苯丙胺(METH)引起的预先存在的神经元损伤。具体地说，一次注射冰毒会导致CD-1小鼠纹状体中多巴胺转运体(DAT)的长期丢失。注射冰毒2周后，60%的DAT被破坏。在注射冰毒后第14天单次注射DADLE，在第16天恢复到接近对照组的DAT水平。在另一项考察冰毒对CD-1小鼠基因组影响的研究中，我们发现DADLE预处理可以缓解即刻早期基因c-fos mRNA水平的升高。因此，我们的结果表明，DADLE可以促进神经元对预先存在的损伤的存活，并且DADLE的这一作用可能涉及到基因组水平的影响。阿片类药物；心肌存活；缺血；甲基苯丙胺；神经毒性；冬眠诱导蛋白；冬眠。

This project examines the physiological effects and the underlying biochemical mechanisms of the action of delta opioid peptide DADLE and a DADLE-related protein HIT (Hibernation Induction Trigger) in tissue survival. In this fiscal year, we found that both DADLE and HIT display similar biological activity in mouse vas deferens bioassay. Further, we have partially sequenced an alpha-1-glycoprotein-like 88 kDa hibernation-related protein in HIT, which may prove to be the blood- borne HIT molecule. The delta opioid peptide DADLE is also found to reverse the pre-existing neuronal damage induced by methamphetamine (METH). Specifically, a single injection of METH causes a long-term loss of dopamine transporters (DAT) in the striatum of CD-1 mouse. Two week after the injection of METH, 60% of DAT was destroyed. A single injection of DADLE, given at day 14 post METH administration, restores the DAT level close to that of controls at day 16. In a separate study examining the genomic effect exerted by METH in CD-1 mice, we found that the elevated level of the mRNA of an immediate early gene, c-fos, is alleviated by a DADLE pretreatment. Thus, our results indicate that DADLE can promote the neuronal survival against pre-existing insults and that this action of DADLE may involve influences at the genomic level. - opioid; myocardiac survival; ischemia; methamphetamine; neurotoxicity; hibernation induction protein; hibernation.