Document Detail

C6 glioma cells differentiated by retinoic acid overexpress the glutamate transporter excitatory amino acid carrier 1 (EAAC1).
MedLine Citation:
PMID:  18207650     Owner:  NLM     Status:  MEDLINE    
The transport of excitatory amino acids (EAA) in CNS is performed by a family of high affinity, sodium dependent carriers. One of these transporters, excitatory amino acid carrier 1 (EAAC1), is known to be regulated by several mechanisms that modify carrier abundance on the plasma membrane. Much less is known on EAAC1 regulation at the level of gene expression. Here we report that, in C6 rat glioma cells, a line recently described to contain neural stem-like cells, EAAC1 is markedly induced by all trans-retinoic acid (ATRA), a well known differentiating agent. Consistently, ATRA stimulates EAA transport, with the maximal effect observed at concentrations>or=1 microM. After 4 days of treatment with 10 microM ATRA, the transport Vmax is fivefold enhanced, Slc1a1 mRNA is increased by 400% compared with control, EAAC1 carrier is sixfold overexpressed and the C6 culture is greatly enriched of cells with bipolar morphology strongly positive for EAAC1 immunoreactivity. Compared with untreated cells, ATRA-treated C6 cells express less Slc1a3 mRNA, for the transporter GLAST, but significantly higher levels of Slc1a2 mRNA, for the transporter GLT-1, although no expression of either protein is detected with Western blot in both untreated and ATRA-treated cells. Consistently, the inhibition pattern of aspartate transport and its stimulation by phorbol esters are indicative of a transport process due to EAAC1 operation. Under the conditions adopted, ATRA treatment causes the induction of proteolipid protein, an oligodendrocytic marker. These results indicate that, in C6 cells, ATRA stimulates the expression of EAAC1, possibly as a step toward oligodendrocytic differentiation, and constitute the first demonstration of the induction of this transporter by a differentiating agent.
M G Bianchi; G C Gazzola; L Tognazzi; O Bussolati
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-12-15
Journal Detail:
Title:  Neuroscience     Volume:  151     ISSN:  0306-4522     ISO Abbreviation:  Neuroscience     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-02-18     Completed Date:  2008-06-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1042-52     Citation Subset:  IM    
Unit of General and Clinical Pathology, Department of Experimental Medicine, University of Parma, Via Volturno, 39, 43100 Parma, Italy.
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MeSH Terms
Antineoplastic Agents / pharmacology*
Aspartic Acid / metabolism,  pharmacology
Cell Differentiation / drug effects*
Cell Line, Tumor
Dose-Response Relationship, Drug
Excitatory Amino Acid Transporter 3 / antagonists & inhibitors,  metabolism*
Excitatory Amino Acids / pharmacology
Gene Expression Regulation, Neoplastic / drug effects*
Glioma / pathology
Nerve Tissue Proteins / metabolism
Tretinoin / pharmacology*
Reg. No./Substance:
0/Antineoplastic Agents; 0/Excitatory Amino Acid Transporter 3; 0/Excitatory Amino Acids; 0/Nerve Tissue Proteins; 0/Slc1a1 protein, rat; 0/benzyloxyaspartate; 302-79-4/Tretinoin; 56-84-8/Aspartic Acid

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