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Protective Effects of Pyridoxal Phosphate Against Glucose Deprivation‐Induced Damage in Cultured Hippocampal Neurons
Author(s) -
Geng MeiYu,
Saito Hiroshi,
Nishiyama Nobuyoshi
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.68062500.x
Subject(s) - aminooxyacetic acid , extracellular , glutamate receptor , intracellular , hippocampal formation , biochemistry , pyridoxal , endocrinology , medicine , chemistry , nmda receptor , lactate dehydrogenase , pyridoxal phosphate , biology , enzyme , receptor , cofactor
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 µ M ) 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.