Regulation of serine racemase activity by D-serine and nitric oxide in human glioblastoma cells

In the human glioblastoma cell line U87, the activity of serine racemase (SR), catalyzing the isomerisation of serine, was inversely regulated by D-serine and nitric oxide (NO), a neuromodulator and a neurotransmitter, respectively. SR activity was dose-dependently enhanced up to five times in cells treated with 10 MM D-serine, whereas it was inhibited by NO. Further-more, D-serine was found to induce the denitrosylation of SR purified from mouse brain. These results suggest that serine racemase activity in astrocyte is regulated inversely by D-serine and NO. SR should be inhibited through nitrosylation by NO and activated through denitrosylation elicited by D-serine. (C) 2005 Elsevier Ireland Ltd. All fights reserved.