Neuroprotective effect of high glucose against NMDA, free radical, and oxygen-glucose deprivation through enhanced mitochondrial potentials.
Cultured cortical neurons maintained in 25 mM glucose underwent a widespread neuronal death after exposure to NMDA, AMPA, and kainate. Among these, NMDA toxicity was substantially reduced in neurons maintained in 100 mM glucose. NMDA-induced increase in [Ca(2+)](i) and reactive oxygen species was attenuated in neurons maintained in high glucose that revealed increased mitochondrial membrane and redox potentials as determined using rhodamine 123 and 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide. p-trifluoromethoxy-phenylhydrazone, KCN, and rotenone, the selective inhibitors of mitochondrial potential, abrogated neuroprotective effect of high glucose against NMDA. The neuroprotective action of high glucose was extended against oxygen or combined oxygen-glucose deprivation. The present study provides evidence that prolonged exposure of cortical cells to high glucose attenuates NMDA- and free radical-mediated neuronal death via enhanced mitochondrial function.
Seo
S Y
SY
Department of Pharmacology, Ajou University School of Medicine, Suwon, Kyungkido, 442-749 Korea.
Kim
E Y
EY
Kim
H
H
Gwag
B J
BJ
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005947:Glucose / Q000008:administration & dosage* / Q000172:deficiency* / Q000494:pharmacology; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000502:physiology*; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000378:metabolism / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D009498:Neurotoxins; D017382:Reactive Oxygen Species; D016202:N-Methylaspartate; D005947:Glucose