酒精的分子效应：揭开酒精神秘作用的线索

The molecular effects of alcohol: clues to the enigmatic action of alcohol.

作者信息

Kumari Meena, Anji Antje, Woods Henri, Ticku Maharaj K

机构信息

Department of Anatomy and Physiology, Kansas State University, Manhattan 66506, USA.

出版信息

Ann N Y Acad Sci. 2003 May;993:82-94; discussion 123-4. doi: 10.1111/j.1749-6632.2003.tb07515.x.

DOI:10.1111/j.1749-6632.2003.tb07515.x

PMID:12853299

Abstract

Chronic ethanol treatment (50 mM, five days) induces stabilization of NR1 receptor subunit mRNA in cultured fetal cortical neurons. In this paper, we investigate the mechanism(s) by which ethanol mediates its effects on NR1 mRNA. Specifically, we have determined if cellular localization of NR1 mRNA in cortical neurons and/or de novo protein synthesis is essential for ethanol-mediated stabilization of NR1 mRNA. Subcellular fractionation studies show that all detectable NR1 mRNA is associated with rough endoplasmic reticulum, indicating that subcellular distribution of NR1 mRNA in fetal cortical neurons does not play a role in ethanol-mediated NR1 mRNA stabilization. However, inhibition of protein synthesis by cycloheximide abolished the mRNA stabilizing effect of ethanol on NR1 mRNA, thus suggesting de novo protein synthesis is crucial for the action of ethanol on NR1 mRNA stabilization.

摘要

慢性乙醇处理（50 mM，持续五天）可诱导培养的胎儿皮质神经元中NR1受体亚基mRNA的稳定性。在本文中，我们研究了乙醇介导其对NR1 mRNA作用的机制。具体而言，我们确定了皮质神经元中NR1 mRNA的细胞定位和/或从头蛋白质合成对于乙醇介导的NR1 mRNA稳定性是否至关重要。亚细胞分级分离研究表明，所有可检测到的NR1 mRNA都与粗面内质网相关，这表明胎儿皮质神经元中NR1 mRNA的亚细胞分布在乙醇介导的NR1 mRNA稳定性中不起作用。然而，环己酰亚胺抑制蛋白质合成消除了乙醇对NR1 mRNA的mRNA稳定作用，因此表明从头蛋白质合成对于乙醇对NR1 mRNA稳定性的作用至关重要。