PROTECTION OF ASTROCYTES BY FRUCTOSE-1,6-BISPHOSPHATE AND CITRATE AMELIORATES NEURONAL INJURY UNDER HYPOXIC CONDITIONS

Fructose 1,6-bisphosphate (FBP) protects astrocytes from hypoxic injur y in vitro. To determine whether FBP and citrate (inhibitors of phosph ofructokinase) ameliorate hypoxia-induced injury to neurons and, if th ey do, whether the protective effects are a direct result of their act ions on neurons or a consequence of their actions on astrocytes, we ad ded FBP or citrate to the media of normoxic and hypoxic 'pure', mixed and co-culture systems, FBP (3.5 mM) and citrate (10 mu M-2 mM) decrea sed release of LDH from astrocytes following 24 h of hypoxia. Eight ho urs of hypoxia killed pure neuronal cultures and neither FBP nor citra te prevented this death. However, in mixed and co-culture systems, FBP and citrate increased neuronal viability (as determined by the ratio of live-to-total cells), even after 47 h of hypoxia. In co-culture, fo llowing 24 h of hypoxia, both FBP and citrate reduced neuronal release of LDH and neuronal death, Fluorocitrate, a suicidal-inhibitor of aco nitase, also protected astrocytes, but not neurons, from hypoxia in 'p ure' culture, presumably by increasing intracellular citrate concentra tions through inhibition of the catalysis of citrate to isocitrate, We conclude that FBP and citrate attenuate hypoxic neuronal injury throu gh their effects on astrocytes.