EFFECT OF 6-AMINONICOTINAMIDE ON METABOLISM OF ASTROCYTES AND C6-GLIOMA CELLS

Brain tissue cells have been shown to use two predominant pathways for energy production. The first of these is the pentose phosphate shunt, and the second is glycolysis, followed by the TCA cycle. Inhibition o f these pathways can result in a reduction of ATP, and changes in the concentration of various metabolites. In the present study, the acute and chronic effect of 6-aminonicotinamide (6-AN) (0.01, 0.02, and 0.03 mg/ml) was examined on astrocytes and C6-glioma cells. Following this treatment, glucose, lactate, glutamate, ATP, and PCr were assayed acc ording to the procedures of Lowry and Passonneau. Our data indicated t hat following 15 minutes treatment of astrocytes and C6-glioma with 6A N there was no significant difference in the concentration of metaboli tes measured. However, following 24 hours treatment there was a signif icant increase in glucose concentration and significant reduction in t he concentration of ATP, PCr, lactate and glutamate in both cell types . Morphological changes appeared later following 48 hours treatment wi th 6-AN in both cell types. Glucose accumulation can be explained by t he fact that it is the precursor to both glycolysis and the pentose ph osphate shunt. If these processes are inhibited, glucose will obviousl y accumulate and products like ATP, PCr, lactate and glutamate will de crease. Additionally, there was significant differences in concentrati on of glucose and lactate between astrocytes and C6-glioma cells. The significance of these differences has been discussed.