Guo Hong, Lai Liching, Butchbach Matthew E R, Lin Chien-liang Glenn
Department of Neuroscience, The Ohio State University, Columbus, 43210, USA.
Mol Cell Neurosci. 2002 Dec;21(4):546-60. doi: 10.1006/mcne.2002.1198.
Abnormal splicing of astroglial glutamate transporter EAAT2 mRNA has been suggested to account for the loss of EAAT2 protein in amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). We have identified several clones of human U251 glioma cells which express varying amounts of aberrantly spliced EAAT2 mRNA; these clones do not express any detectable EAAT2 protein. When the wild-type EAAT2 cDNA was expressed in each of these clones, we found that the amount of EAAT2 protein inversely correlated with the levels of endogenous aberrant EAAT2 mRNA. We also observed that ectopic expression of normal EAAT2 protein is toxic to U251 cells as well as to undifferentiated primary astrocytes. We conclude that expression of aberrant EAAT2 mRNA may be one possible mechanism to repress normal EAAT2 protein expression. The implication of this study for the mechanisms of EAAT2 protein loss in ALS and AD is discussed.
星形胶质细胞谷氨酸转运体EAAT2 mRNA的异常剪接被认为是肌萎缩侧索硬化症（ALS）和阿尔茨海默病（AD）中EAAT2蛋白缺失的原因。我们鉴定了几个人类U251胶质瘤细胞克隆，它们表达不同量的异常剪接的EAAT2 mRNA；这些克隆不表达任何可检测到的EAAT2蛋白。当野生型EAAT2 cDNA在这些克隆中的每一个中表达时，我们发现EAAT2蛋白的量与内源性异常EAAT2 mRNA的水平呈负相关。我们还观察到正常EAAT2蛋白的异位表达对U251细胞以及未分化的原代星形胶质细胞有毒性。我们得出结论，异常EAAT2 mRNA的表达可能是抑制正常EAAT2蛋白表达的一种可能机制。本文讨论了该研究对ALS和AD中EAAT2蛋白缺失机制的意义。
