Human glioma cells and undifferentiated primary astrocytes that express aberrant EAAT2 mRNA inhibit normal EAAT2 protein expression and prevent cell death.
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.
Guo
Hong
H
Department of Neuroscience, The Ohio State University, Columbus, 43210, USA.
Lai
Liching
L
Butchbach
Matthew E R
ME
Lin
Chien-liang Glenn
CL
D020121:5' Untranslated Regions / Q000235:genetics; D017398:Alternative Splicing / Q000235:genetics*; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001253:Astrocytes / Q000378:metabolism*; D002999:Clone Cells / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000172:deficiency* / Q000235:genetics* / Q000633:toxicity; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D005910:Glioma; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D009435:Synaptic Transmission / Q000235:genetics; D014407:Tumor Cells, Cultured
D020121:5' Untranslated Regions; D027342:Excitatory Amino Acid Transporter 2; D014179:Neurotransmitter Uptake Inhibitors; D012333:RNA, Messenger; D018698:Glutamic Acid