Protective effects of pyridoxal phosphate against glucose deprivation-induced damage in cultured hippocampal neurons.
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.
Geng
M Y
MY
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Japan.
Saito
H
H
Nishiyama
N
N
D000255:Adenosine Triphosphate / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000172:deficiency / Q000494:pharmacology*; D018698:Glutamic Acid / Q000633:toxicity; D006624:Hippocampus / Q000166:cytology; D007003:Hypoglycemia / Q000188:drug therapy; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011732:Pyridoxal Phosphate / Q000494:pharmacology*; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000596:Amino Acids; D018696:Neuroprotective Agents; D018698:Glutamic Acid; D011732:Pyridoxal Phosphate; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D005947:Glucose