EFFECT OF FRUCTOSE-1,6-BISPHOSPHATE ON GLUTAMATE UPTAKE AND GLUTAMINE-SYNTHETASE ACTIVITY IN HYPOXIC ASTROCYTE CULTURES

Astrocytes are important in regulating the microenvironment of neurons both by catabolic and synthetic pathways. The glutamine synthetase (G S) activity observed in astrocytes affects neurons by removing toxic s ubstances, NH3 and glutamate; and by providing an important neuronal s ubstrate, glutamine. This glutamate cycle might play a critical role d uring periods of hypoxia and ischemia, when an increase in extracellul ar excitatory amino acids is observed. It was previously shown in our laboratory that fructose-1,6-bisphosphate (FBP) protected cortical ast rocyte cultures from hypoxic insult and reduced ATP loss following a p rolonged (18-30 hrs) hypoxia. In the present study we established the effects of mBP on the level of glutamate uptake and GS activity under normoxic and hypoxic conditions. Under normoxic conditions, [U-C-14]gl utamate uptake and glutamine production were independent of FBP treatm ent; whereas under hypoxic conditions, the initial increase in glutama te uptake and an overall increase in glutamine production in astrocyte s were FBP-dependent. Glutamine synthetase activity was dependent on F BP added during the 22 hours of either normoxic- or hypoxic-treatment, hence significant increases in activity were observed due to FBP rega rdless of the oxygen/ATP levels in situ. These studies suggest that ac tivation of GS by FBP may provide astrocytic protection against hypoxi c injury.