Nitric oxide-enhanced excitotoxity-independent apoptosis of glucose-deprived neurons

Won Ki Kim, Jang Hyun Chung, Hyoung Chun Kim, Kwang Ho Ko

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Glucose deprivation has been shown to elicit neuronal death via extracellular glutamate accumulation. Here we report that immunostimulated glial expression of inducible nitric oxide synthase enhances the apoptotic death of glucose-deprived cerebellar granule cells (CGC) via the excitotoxicity-independent pathway. CGC cultures were immunostimulated by interferon-γ (100 U/ml) and lipopolysaccharides (1 μg/ml) and 2 days later were challenged by glucose deprivation. Neither a 2-h Glucose deprivation nor a 2-day immunostimulation altered the viability of CGC. A 2-day immunostimulation, however, markedly enhanced the apoptotic death of CGC glucose-deprived for 1 h. The increased apoptotic death of glucose-deprived CGC after immunostimulation was mimicked by the nitric oxide (NO) releasing reagent 3-morpholinosydnonimine (200 μM, 30 min) and was partially prevented by the NO synthase (NOS) inhibitor N(G)-nitroarginine. The enhanced apoptotic death was not blocked by the N-methyl-d-aspartate (NMDA) receptor antagonists d-2-amino-5-phosphovalerate (APV) and dizocilpine (MK-801) or the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Moreover, the NO-induced enhanced apoptotic death occurred without a significant increase of the concentration of glutamate in the bathing medium. Our data indicate that immunostimulated glial cells potentiate the apoptotic death of glucose-deprived CGC in part through the expression of inducible NOS but not through NMDA receptor activation. Potentiation of glucose-deprived CGC death by immunostimulated glial cells may be clinically implicated in the tendency of recurrent ischemic insults to be more severe and fatal than an initial ischemic insult. Copyright (C) 1999 Elsevier Science Ireland Ltd.

Original languageEnglish
Pages (from-to)281-289
Number of pages9
JournalNeuroscience Research
Volume33
Issue number4
DOIs
Publication statusPublished - 1999 Apr
Externally publishedYes

Keywords

  • Apoptosis
  • Cerebellar granule cells (CGC)
  • Cycloheximide
  • DNA fragmentation
  • Glucose-deprivation
  • Glutamate
  • Nitric oxide (NO)

ASJC Scopus subject areas

  • Neuroscience(all)

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