From: Doug Skrecky (oberon@vcn.bc.ca)
Date: Tue Dec 05 2000 - 10:35:41 MST
Title
Protective effects of
pyridoxal phosphate against glucose
deprivation-induced damage in cultured hippocampal neurons.
Source
Journal of Neurochemistry. 68(6):2500-6, 1997 Jun.
Abstract
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.
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