Specific regulation of rat glial cell line-derived neurotrophic factor gene expression by riluzole in C6 glioma cells

Journal of Neurochemistry
Anne-Sophie CaumontEmmanuel Hermans

Abstract

Contrasting with its robust expression during embryogenesis, the glial cell line-derived neurotrophic factor (GDNF) is repressed in the adult organism. However, rapid induction of this neuronal growth factor is observed following diverse neuronal insults and it is now widely accepted that the control of its expression could constitute a powerful target in neuropharmacology. We investigated the effects of the neuroprotective drug, riluzole, on the GDNF gene expression in glial cells. Exposure of C6 glioma cells to riluzole (1 microM) significantly increased GDNF protein and mRNA levels. Using luciferase reporter gene constructs encoding fragments of the 5' untranslated region of the rat GDNF gene, we demonstrated that riluzole mediates its effect at the transcription level. Furthermore, luciferase assays revealed the presence of a negative regulatory region within the +343/+587 region of exon 1. This region was shown to contribute to the high sensitivity and specificity of the induction mediated by riluzole in the C6 glioma cell line at pharmacologically relevant concentrations. The effects of riluzole were inhibited by the mitogen-activated protein kinase extracellular signal-related kinase (MEK) inhibitor PD 98059. Together, t...Continue Reading

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Citations

Mar 10, 2010·Apoptosis : an International Journal on Programmed Cell Death·Yan Wang, Zheng-Hong Qin
Jun 19, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Hung-Ming WuRu-Band Lu
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Jan 19, 2017·Reviews in the Neurosciences·Anton S TsybkoNina K Popova

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