Geng M Y, Saito H, Nishiyama N
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Japan.
J Neurochem. 1997 Jun;68(6):2500-6. doi: 10.1046/j.1471-4159.1997.68062500.x.
When hippocampal cultures were deprived of glucose, massive release of lactate dehydrogenase (LDH), an indicator of neuronal death, occurred via NMDA receptor activation. Addition of pyridoxal phosphate (PLP; 1 and 10 microM) inhibited this LDH release in a concentration-dependent manner. Prior exposure to PLP evoked more potent inhibitory effects on LDH release compared with those treated at the onset of glucose deprivation. Furthermore, PLP inhibited the reduction of intracellular content of pyruvate induced by glucose deprivation, which was accompanied by the reversal of intracellular ATP depletion. A noteworthy elevation of extracellular glutamate in response to glucose deprivation was completely reversed by addition of PLP. Aminooxyacetic acid, a potent inhibitor of PLP-dependent enzymes, antagonized the effects of PLP on LDH release, pyruvate production, and ATP formation. These results suggest that PLP protects neurons from glucose deprivation-induced damage by enhancing the formation of energy-yielding products and relieving extracellular load of glutamate. The observed phenomena further indicate that PLP might be used prophylactically against neuronal death induced by metabolic disorders.
当海马体培养物被剥夺葡萄糖时，作为神经元死亡指标的乳酸脱氢酶（LDH）会通过NMDA受体激活而大量释放。添加磷酸吡哆醛（PLP；1和10微摩尔）以浓度依赖的方式抑制了这种LDH释放。与在葡萄糖剥夺开始时处理的情况相比，预先暴露于PLP对LDH释放产生了更强的抑制作用。此外，PLP抑制了由葡萄糖剥夺诱导的细胞内丙酮酸含量的降低，这伴随着细胞内ATP消耗的逆转。添加PLP完全逆转了因葡萄糖剥夺而导致的细胞外谷氨酸显著升高。氨基氧乙酸是一种有效的PLP依赖性酶抑制剂，它拮抗了PLP对LDH释放、丙酮酸产生和ATP形成的作用。这些结果表明，PLP通过增强能量产生产物的形成和减轻细胞外谷氨酸负荷来保护神经元免受葡萄糖剥夺诱导的损伤。观察到的现象进一步表明，PLP可能可用于预防代谢紊乱引起的神经元死亡。
