Kumari M, Ticku M K
Department of Pharmacology, University of Texas Health Science Center, San Antonio 78284-7764, USA.
J Neurochem. 1998 Apr;70(4):1467-73. doi: 10.1046/j.1471-4159.1998.70041467.x.
Previous studies have shown that chronic ethanol treatment up-regulates the expression of the N-methyl-D-aspartate (NMDA) receptor number and function both in vitro and in vivo. In vitro chronic ethanol treatment specifically augments mRNA levels of the R2B subunit without altering R1 subunit mRNA levels, although similar treatment results in increased levels of both R1 and R2B polypeptides. To further delineate the molecular mechanisms involved in differential regulation of NMDA receptor subunits by chronic ethanol treatment (50 mM, 5 days), we have determined the mRNA stability of the NMDA R1 and R2B subunits and the transcription rate of the respective genes using mouse fetal cortical neurons. Our observations demonstrated that ethanol stabilized the NMDA R1 mRNA over the time period examined (24 h) without altering the stability of the R2B mRNA. Chronic exposure of fetal cortical neurons to ethanol enhanced the rate of R2B gene transcription approximately twofold. Taken together, these results suggest that up-regulation of the NMDA receptor number seen in cultured cortical neurons after chronic ethanol treatment is due to the regulation of the NMDA R2B receptor subunit at the transcriptional level and that of the NMDA R1 subunit mainly at the posttranscriptional level.
先前的研究表明，慢性乙醇处理在体外和体内均上调N-甲基-D-天冬氨酸（NMDA）受体的表达数量及功能。体外慢性乙醇处理可特异性增加R2B亚基的mRNA水平，而不改变R1亚基的mRNA水平，尽管类似处理会导致R1和R2B多肽水平均升高。为了进一步阐明慢性乙醇处理（50 mM，5天）对NMDA受体亚基差异调节所涉及的分子机制，我们利用小鼠胎儿皮质神经元测定了NMDA R1和R2B亚基的mRNA稳定性以及各自基因的转录速率。我们的观察结果表明，在所检测的时间段（24小时）内，乙醇使NMDA R1 mRNA稳定，而不改变R2B mRNA的稳定性。胎儿皮质神经元长期暴露于乙醇使R2B基因转录速率提高了约两倍。综上所述，这些结果表明，慢性乙醇处理后培养的皮质神经元中NMDA受体数量的上调是由于NMDA R2B受体亚基在转录水平的调节以及NMDA R1亚基主要在转录后水平的调节所致。
