Abbreviations used : DMEM, Dulbecco's modified Eagle's medium ; GAD, glutamic acid decarboxylase ; GVG, γ-vinyl-GABA ; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide ; TCA cycle, tricarboxylic acid cycle.
Glutamic Acid Decarboxylase-Expressing Astrocytes Exhibit Enhanced Energetic Metabolism and Increase PC12 Cell Survival Under Glucose Deprivation
Version of Record online: 25 DEC 2001
Journal of Neurochemistry
Volume 75, Issue 1, pages 56–64, July 2000
How to Cite
Bellier, J.P., Sacchettoni, S., Prod'hon, C., Perret-Liaudet, A., Belin, M.F. and Jacquemont, B. (2000), Glutamic Acid Decarboxylase-Expressing Astrocytes Exhibit Enhanced Energetic Metabolism and Increase PC12 Cell Survival Under Glucose Deprivation. Journal of Neurochemistry, 75: 56–64. doi: 10.1046/j.1471-4159.2000.0750056.x
- Issue online: 25 DEC 2001
- Version of Record online: 25 DEC 2001
- Glutamic acid decarboxylase transgene;
- Energetic metabolism;
- PC12 cells
Abstract : Astrocytes play a key role by catabolizing glutamate from extracellular space into glutamine and tricarboxylic acid components. We previously produced an astrocytic cell line that constitutively expressed glutamic acid decarboxylase (GAD67), which converts glutamate into GABA to increase the capacity of astrocytes to metabolize glutamate. In this study, GAD-expressing astrocytes in the presence of glutamate were shown to have increased energy metabolism, as determined by a moderate increase of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction, by an increased ATP level, and by enhanced lactate release. These changes were due to GAD transgene expression because transient expression of a GAD antisense plasmid resulted in partial suppression of the ATP level increase. These astrocytes had an increased survival in response to glucose deprivation in the presence of glutamate compared with the parental astrocytes, and they were also able to enhance survival of a neuronal-like cell line (PC12) under glucose deprivation. This protection may be partially due to the increased lactate release by GAD-expressing astrocytes because PC12 cell survival was enhanced by lactate and pyruvate under glucose deprivation. These results suggest that the establishment of GAD expression in astrocytes enhancing glutamate catabolism could be an interesting strategy to increase neuronal survival under hypoglycemia conditions.