We have previously reported that the production of nitric oxide (NO) in immunostimulated astrocytes was markedly decreased under glucose-deprived conditions. The present study was undertaken to find the contributing factor(s) for the decreased NO production in glucose-deprived immunostimulated astrocytes. NO production in rat primary astrocytes was stimulated for 24-48 h by cotreatment with lipopolysaccharides (1 μg/ml) and interferon-γ (100 U/ml). Decreased NO production in immunostimulated astrocytes by glucose deprivation was mimicked by the glycolytic inhibitor 2-deoxyglucose and reversed by addition of pyruvate and lactate. Glucose deprivation did not alter the expression of inducible nitric oxide synthase (iNOS) in immunostimulated astrocytes. Addition of β-NADPH, but not tetrahydrobiopterine, both of which are essential cofactors for NOS function, completely restored the NO production that was decreased in glucose-deprived immunostimulated astrocytes. Glucose deprivation and immunostimulation synergistically reduced intracellular NADPH level in astrocytes. The results indicate that glucose deprivation decreases NO production in immunostimulated astrocytes by depleting intracellular NADPH, a cofactor of iNOS.
- Cell death
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