OPIOIDS AND CELLULAR SURVIVAL

阿片类药物与细胞存活

• 批准号: 6289603
• 负责人: Tsung-Ping Ping Su
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6289603
• 关键词: endogenous opioid; heart function; heart preservation; heart transplantation; laboratory rabbit; lung; lung transplantation; myocardial ischemia /hypoxia; nonhuman therapy evaluation; perfusion; respiratory function; tissue /organ preservation

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.

该项目研究了δ阿片肽DADLE和DADLE相关蛋白HIT（冬眠诱导触发器）在组织存活中的生理作用和潜在的生化机制。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，我们对HIT中的α-1-糖蛋白样88 kDa冬眠相关蛋白进行了部分测序，这可能证明是血液传播的HIT分子。还发现δ阿片肽DADLE逆转由甲基苯丙胺（METH）诱导的预先存在的神经元损伤。具体地，单次注射METH导致CD-1小鼠纹状体中多巴胺转运蛋白（DAT）的长期损失。注射METH后2周，DAT破坏率达60%。在METH施用后第14天给予的DADLE的单次注射使DAT水平在第16天恢复至接近对照的DAT水平。在一项单独的研究中，检查了METH在CD-1小鼠中产生的基因组效应，我们发现DADLE预处理减轻了即刻早期基因c-fos mRNA水平的升高。因此，我们的研究结果表明，DADLE可以促进神经元的生存对预先存在的侮辱，这一行动的DADLE可能涉及在基因组水平上的影响。- 阿片类;心肌存活;缺血;甲基苯丙胺;神经毒性;冬眠诱导蛋白;冬眠。