دورية أكاديمية
A polymorphism in the EAAT2promoter is associated with higher glutamate concentrations and higher frequency of progressing stroke
| العنوان: | A polymorphism in the EAAT2promoter is associated with higher glutamate concentrations and higher frequency of progressing stroke |
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| المؤلفون: | Mallolas, Judith, Hurtado, Olivia, Castellanos, Mar, Blanco, Miguel, Sobrino, Tomás, Serena, Joaquín, Vivancos, José, Castillo, José, Lizasoain, Ignacio, Moro, María A., Dávalos, Antoni |
| المصدر: | The Journal of Experimental Medicine ; volume 203, issue 3, page 711-717 ; ISSN 1540-9538 0022-1007 |
| بيانات النشر: | Rockefeller University Press |
| سنة النشر: | 2006 |
| الوصف: | It remains unclear why some individuals are susceptible to excitotoxicity after stroke. A possible explanation is impaired glutamate uptake. We have found a highly prevalent polymorphism in the promoter of the glutamate transporter EAAT2 gene that abolishes a putative regulatory site for activator protein–2 (AP-2) and creates a new consensus binding site for the repressor transcription factor GC-binding factor 2 (GCF2). The mutant genotype is associated with increased plasma glutamate concentrations and with a higher frequency of early neurological worsening in human stroke. After transfection into astrocytes, the mutant promoter was not activated by AP-2 and was effectively repressed by GCF2, and its activity in the presence of GCF2 was reduced when compared with the AP-2–cotransfected wild-type promoter. We also show that GCF2 is expressed in ischemic rat brain, suggesting that decreased glutamate uptake occurs in individuals carrying the mutation after stroke. These findings may explain individual susceptibility to excitotoxic damage after stroke as well as the failure of glutamate antagonists in those patients without this polymorphism. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1084/jem.20051979 |
| الإتاحة: | https://doi.org/10.1084/jem.20051979Test https://rupress.org/jem/article-pdf/203/3/711/1723260/711.pdfTest |
| رقم الانضمام: | edsbas.7B2D5B73 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1084/jem.20051979 |
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