Enhanced neuronal protection from oxidative stress by coculture with glutamic acid decarboxylase-expressing astrocytes.
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.
Lamigeon
C
C
Laboratoires de Neuro-Virologie Moléculaire et de Neurobiologie Expérimentale et Physiopathologie, INSERM U433, Faculté de Médecine RTH Laënnec Lyon, France.
Bellier
J P
JP
Sacchettoni
S
S
Rujano
M
M
Jacquemont
B
B
D000818:Animals; D001253:Astrocytes / Q000201:enzymology* / Q000502:physiology; D002454:Cell Differentiation; D018920:Coculture Techniques; D016895:Culture Media, Serum-Free; D004734:Energy Metabolism; D005813:Genes, Synthetic; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D005968:Glutamate Decarboxylase / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018698:Glutamic Acid / Q000494:pharmacology / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D016716:PC12 Cells / Q000166:cytology / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014162:Transfection; D019076:Transgenes
D016895:Culture Media, Serum-Free; D005904:Glial Fibrillary Acidic Protein; D007527:Isoenzymes; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D018698:Glutamic Acid; D006861:Hydrogen Peroxide; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D005978:Glutathione