title: Methyl-beta-cyclodextrin but not retinoic acid reduces EAAT3-mediated glutamate uptake and increases GTRAP3-18 expression.
abstract: The Na+-dependent glutamate transporter EAAT3 facilitates glutamate uptake into neurons as well as many other cell types. GTRAP3-18 (JWA, Arl6ip5) is a novel protein that interacts with EAAT3 and negatively modulates EAAT3-mediated glutamate uptake. Previous studies suggest that retinoic acid (RA) decreases Na+-dependent glutamate uptake and increases GTRAP3-18 protein expression. However, the RA used in those studies was complexed with methyl-beta-cyclodextrin (MebetaCD). In the present study we found that MebetaCD, but not RA, significantly reduced Na+-dependent EAAT3-mediated [3H]glutamate uptake in human embryonic kidney 293 (HEK293) cells. MebetaCD also significantly increased GTRAP3-18 protein expression in HEK293 cells as well as in rat hypothalamic neuron cultures. Intracerebroventricular administration of MebetaCD to the mouse brain resulted in a significant increase in GTRAP3-18 immunoreactivity in the hippocampus and cerebral cortex. In conclusion, we have shown that MebetaCD reduces EAAT3-mediated glutamate uptake and induces the expression of GTRAP3-18 protein.
authors.affiliation: Department of Neuroscience, Ohio State Biochemistry Program, The Ohio State University, 333 West 10th Avenue, Columbus, OH 43210-1239, USA.
authors.forename: Matthew E R
authors.initials: ME
authors.lastname: Butchbach
authors.forename: Hong
authors.initials: H
authors.lastname: Guo
authors.forename: Chien-liang Glenn
authors.initials: CL
authors.lastname: Lin
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003505:Cyclodextrins / Q000008:administration & dosage / Q000494:pharmacology*; D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000493:pharmacokinetics*; D006360:Heat-Shock Proteins; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007031:Hypothalamus / Q000166:cytology; D007276:Injections, Intraventricular; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D027981:Symporters / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*; D047392:beta-Cyclodextrins
chemical_list: D027322:Amino Acid Transport System X-AG; C464502:Arl6ip5 protein, mouse; D002352:Carrier Proteins; D003505:Cyclodextrins; D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; D006360:Heat-Shock Proteins; D026901:Membrane Transport Proteins; C493400:SLC1A1 protein, human; C493399:Slc1a1 protein, mouse; D027981:Symporters; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D018698:Glutamic Acid; D014212:Tretinoin; D012964:Sodium