EFFECT OF OROTIC-ACID ON THE METABOLISM OF CEREBRAL CORTICAL ASTROCYTES DURING HYPOXIA AND REOXYGENATION - AN NMR-SPECTROSCOPY STUDY

Astrocytes were incubated under normoxic or hypoxic conditions in Dulb ecco's minimum essential medium containing [2-C-13]acetate, unlabeled glucose and in some cases erotic acid, an intermediate in pyrimidine b iosynthesis, After 12 hr the medium was replaced by fresh medium witho ut drug and incubation was continued for 17 hr in a normal oxygen atmo sphere (reoxygenation), Thereafter, medium was removed, cell extracts were prepared, and metabolism in the treatment group was compared to t he untreated hypoxia group and to control, C-13 and H-1 NMR spectra re vealed that C-13 enrichment in citrate and glutamine C-4 in the initia l medium were increased in the presence of erotic acid, compared to th e untreated hypoxia group but lower than control, The drug increased a cetate utilization during hypoxia to normoxic levels, Thus it appears that the treatment group had a more active mitochondrial metabolism, w hich was also reflected in higher intracellular uridine diphosphoryl s ugars and ADP concentrations, Glutamine labeling was increased in the cell extracts in the presence of erotic acid, Thus it appears that, in the presence of the pyrimidine nucleotide precursor, astrocytes are c apable of normal metabolism during hypoxia which might have implicatio ns for neuronal survival during low oxygen insults, since neurons are dependent on astrocyte produced precursors for their neurotransmitter synthesis. (C) 1998 Wiley-Liss, Inc.