1. Enhanced neuronal protection from oxidative stress by coculture with glutamic acid decarboxylase-expressing astrocytes.
- Author
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Lamigeon C, Bellier JP, Sacchettoni S, Rujano M, and Jacquemont B
- Subjects
- Animals, Astrocytes physiology, Cell Differentiation, Coculture Techniques, Culture Media, Serum-Free, Energy Metabolism, Genes, Synthetic, Glial Fibrillary Acidic Protein genetics, Glutamate Decarboxylase biosynthesis, Glutamate Decarboxylase genetics, Glutamic Acid pharmacology, Glutamic Acid toxicity, Glutathione metabolism, Hydrogen Peroxide pharmacology, Isoenzymes biosynthesis, Isoenzymes genetics, Mice, Neoplasm Proteins biosynthesis, Neoplasm Proteins genetics, Neoplasm Proteins physiology, Nerve Tissue Proteins biosynthesis, Nerve Tissue Proteins genetics, Neurons metabolism, Oxidation-Reduction, Oxidative Stress, PC12 Cells cytology, PC12 Cells metabolism, Promoter Regions, Genetic, Rats, Recombinant Fusion Proteins biosynthesis, Transfection, Transgenes, Astrocytes enzymology, Glutamate Decarboxylase physiology, Isoenzymes physiology, Nerve Tissue Proteins physiology, Neurons cytology
- Abstract
Astrocytes expressing glutamic acid decarboxylase GAD67 directed by the glial fibrillary acidic protein promoter were shown to provide enhanced protection of PC12 cells from H(2)O(2) treatment and serum deprivation in the presence of glutamate. In addition, they protected non-differentiated, but not differentiated, embryonic rat cortical neurons from glutamate toxicity. Glutamic acid decarboxylase (GAD)-expressing astrocytes showed increased glutathione synthesis and release compared to control astrocytes. These changes were due to GAD transgene expression, as transient expression of a GAD antisense plasmid resulted in partial suppression of the increase in glutathione release. In addition to the previously demonstrated increases in NADH and ATP levels and lactate release, GAD-expressing astrocytes show increased antioxidant activity, explaining their ability to protect neurons from various injuries.
- Published
- 2001
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