Document Detail

The food-associated fungal neurotoxin ochratoxin A inhibits the absorption of glutamate by astrocytes through a decrease in cell surface expression of the excitatory amino-acid transporters GLAST and GLT-1.
MedLine Citation:
PMID:  20558201     Owner:  NLM     Status:  MEDLINE    
The food-associated mycotoxin ochratoxin A (OTA) has been demonstrated to be deleterious to numerous cell types including brain cells. Although OTA has been proved to be toxic to astrocytes, no other investigation has been conducted on the impact of OTA on astrocytic functions. In the present study, we evaluated the effect of OTA on one of the major astrocytic functions, i.e. the reabsorption of extracellular glutamate. We found that OTA suppressed glutamate absorption by rat cortical astrocytes with a half inhibitory concentration of 1.3 and 10.1 microM in the absence and presence of fetal calf serum. Although OTA inhibits glutamine synthetase activity, this effect was not involved in OTA-mediated alteration of glutamate absorption since decrease in enzyme activity only occurred at high cytotoxic concentrations of toxin (100 microM). Similarly, alterations in the expression of the excitatory amino-acid transporters were not involved since OTA failed to modify total expression level of GLAST and GLT-1. We found that inhibition of glutamate absorption by OTA was due to a decrease in the expression of GLAST and GLT-1 at the cell surface. We propose that, in addition to being directly toxic to neurons and astrocytes, OTA could also cause the death of brain cells through inhibition of glutamate uptake by astrocytes, leading to the accumulation of extracellular glutamate and ultimately to excitotoxicity.
Helisoa Razafimanjato; Nicolas Garmy; Xiao-Jun Guo; Karine Varini; Coralie Di Scala; Eric Di Pasquale; Nadira Taïeb; Marc Maresca
Publication Detail:
Type:  Journal Article     Date:  2010-06-15
Journal Detail:
Title:  Neurotoxicology     Volume:  31     ISSN:  1872-9711     ISO Abbreviation:  Neurotoxicology     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-06     Completed Date:  2010-12-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7905589     Medline TA:  Neurotoxicology     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  475-84     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Laboratoire des Interactions Moléculaires et Systèmes Membranaires, CRN2M, CNRS UMR 6231, INRA USC 2027, University of Aix-Marseille 2 and Aix-Marseille 3, Faculté des Sciences de St-Jérôme, 13397 Marseille Cedex 20, France.
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MeSH Terms
Analysis of Variance
Animals, Newborn
Astrocytes / cytology,  drug effects*
Cell Membrane / drug effects,  metabolism
Cell Survival / drug effects
Cells, Cultured
Cerebral Cortex / cytology
Dose-Response Relationship, Drug
Excitatory Amino Acid Transporter 1 / genetics,  metabolism*
Excitatory Amino Acid Transporter 2 / genetics,  metabolism*
Gene Expression Regulation / drug effects
Glutamate-Ammonia Ligase / metabolism
Glutamic Acid / metabolism*
Neurotoxins / pharmacology*
Ochratoxins / pharmacology*
Rats, Wistar
Time Factors
Reg. No./Substance:
0/Excitatory Amino Acid Transporter 1; 0/Excitatory Amino Acid Transporter 2; 0/Neurotoxins; 0/Ochratoxins; 303-47-9/ochratoxin A; 56-86-0/Glutamic Acid; EC Ligase

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