title: Up-regulated GLT-1 resists glutamate toxicity and attenuates glutamate-induced calcium loading in cultured neurocytes.
abstract: Glutamate transporter-1 (GLT-1) plays a dual role in glutamate transportation: both normally devotion to the clearance of glutamate and during some pathological conditions extruding glutamate to the extracellular space. Therefore, it is uncertain whether increased expression of GLT-1 will actually be helpful against glutamate excitotoxicity. In this study, GLT-1 up-regulation was induced by ceftriaxone, and L-glutamate was added to induce glutamate toxicity in primary cultured rat cortical cells. The results showed that up-regulated GLT-1 induced by 1 μM ceftriaxone for 2 days markedly increased cell viability, decreased apoptotic cell death and alleviated ultrastructural damage induced by 50 μM glutamate 15 min. as well as promoted L-[(3) H]-glutamate uptake in cultured cells. GLT-1 up-regulation had no effect on the intracellular free calcium concentration ([Ca(2+) ](i) ) in the resting situation, while relieved intracellular calcium overloading by reducing the elevation and promoting the recovery of [Ca(2+) ](i)  following stimulation of 50 μM glutamate for 2 min. Applying 100 μM dihydrokainic acid (GLT-1 antagonist) 30 sec. before glutamate eliminated the above effect of GLT-1 up-regulation on [Ca(2+) ](i) . In conclusion, GLT-1 up-regulation induced by ceftriaxone plays a positive glutamate transporting role against glutamate toxicity in primary cultured rat cortical cells.
authors.affiliation: Department of Neurology, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Chun-hua
authors.initials: CH
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Jiao
authors.forename: Zhao-hui
authors.initials: ZH
authors.lastname: Guo
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.forename: Wei-zhi
authors.initials: WZ
authors.lastname: Wang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002443:Ceftriaxone / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation
chemical_list: D027342:Excitatory Amino Acid Transporter 2; C493395:Slc1a2 protein, rat; D018698:Glutamic Acid; D002443:Ceftriaxone; D002118:Calcium