Glutamic acid decarboxylase-expressing astrocytes exhibit enhanced energetic metabolism and increase PC12 cell survival under glucose deprivation.
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.
Bellier
J P
JP
Laboratoires de Neuro-Virologie Moléculaire et de Neurobiologie Expérimentale et Physiopathologie, INSERM U. 433, France.
Sacchettoni
S
S
Prod'hon
C
C
Perret-Liaudet
A
A
Belin
M F
MF
Jacquemont
B
B
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000201:enzymology*; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned; D004734:Energy Metabolism; D015870:Gene Expression; D005947:Glucose / Q000008:administration & dosage* / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000235:genetics*; D006003:Glycogen / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics; D019344:Lactic Acid / Q000378:metabolism / Q000494:pharmacology; D016716:PC12 Cells; D019289:Pyruvic Acid / Q000494:pharmacology; D051381:Rats; D014162:Transfection; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis
D017077:Culture Media, Conditioned; D007527:Isoenzymes; D019344:Lactic Acid; D005680:gamma-Aminobutyric Acid; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D006003:Glycogen; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D005947:Glucose