Immunostimulated glial cells potentiate glucose deprivation-induced death of cultured rat cerebellar granule cells

Won-Ki Kim, Dong Ook Seo, Jung J. Choi, Kwang H. Ko

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The present study investigates whether immunostimulated glial expression of inducible nitric oxide synthase influences the glucose deprivation- induced death of rat cerebellar granule cells (CGC). CGC/glia cocultures were immunostimulated by interferon-γ (200 U/ml) and lipopolysaccharides (1 μg/ml) and 2 days later were challenged by glucose deprivation. Neurotoxicity was assessed by measuring the release of lactate dehydrogenase. Neither a 2-h glucose deprivation nor a 2-day immunostimulation altered the viability of CGC. A 2-day immunostimulation, however, markedly potentiated the glucose deprivation-induced death of CGC. The increased death of glucose- deprived CGC after immunostimulation was mimicked by the nitric oxide (NO) releasing reagent 3-morpholinosydnonimine (SIN-1) and was partially prevented by the NO synthase (NOS) inhibitor N(G)-nitroarginine. The increased death of glucose-deprived CGC either after immunostimulation or by SIN-1 was not altered by various N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists. Because superoxide dismutase and catalase, which remove superoxide anion, decreased the augmented death of glucose-deprived immunostimulated CGC, the reaction of NO with superoxide to form peroxynitrite appears to be implicated in the potentiated neurotoxicity. Our data indicate that immunostimulated glial cells potentiate the death of glucose-deprived neurons 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.

Original languageEnglish
Pages (from-to)415-424
Number of pages10
JournalJournal of Neurotrauma
Volume16
Issue number5
Publication statusPublished - 1999 May 1
Externally publishedYes

Fingerprint

Neuroglia
Glucose
Immunization
Nitric Oxide Synthase
Superoxides
Nitric Oxide
Cell Death
D-Aspartic Acid
Peroxynitrous Acid
Nitroarginine
Nitric Oxide Synthase Type II
N-Methylaspartate
Coculture Techniques
N-Methyl-D-Aspartate Receptors
L-Lactate Dehydrogenase
Catalase
Interferons
Superoxide Dismutase
Lipopolysaccharides
Neurons

Keywords

  • Cerebellar granule cells (CGC)
  • Glia
  • Ischemia
  • N-methyl-D-aspartate (NMDA)
  • Neurotoxicity
  • Nitric oxide (NO)

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Immunostimulated glial cells potentiate glucose deprivation-induced death of cultured rat cerebellar granule cells. / Kim, Won-Ki; Seo, Dong Ook; Choi, Jung J.; Ko, Kwang H.

In: Journal of Neurotrauma, Vol. 16, No. 5, 01.05.1999, p. 415-424.

Research output: Contribution to journalArticle

@article{21a56efa65ef452186ed88aed849a55f,
title = "Immunostimulated glial cells potentiate glucose deprivation-induced death of cultured rat cerebellar granule cells",
abstract = "The present study investigates whether immunostimulated glial expression of inducible nitric oxide synthase influences the glucose deprivation- induced death of rat cerebellar granule cells (CGC). CGC/glia cocultures were immunostimulated by interferon-γ (200 U/ml) and lipopolysaccharides (1 μg/ml) and 2 days later were challenged by glucose deprivation. Neurotoxicity was assessed by measuring the release of lactate dehydrogenase. Neither a 2-h glucose deprivation nor a 2-day immunostimulation altered the viability of CGC. A 2-day immunostimulation, however, markedly potentiated the glucose deprivation-induced death of CGC. The increased death of glucose- deprived CGC after immunostimulation was mimicked by the nitric oxide (NO) releasing reagent 3-morpholinosydnonimine (SIN-1) and was partially prevented by the NO synthase (NOS) inhibitor N(G)-nitroarginine. The increased death of glucose-deprived CGC either after immunostimulation or by SIN-1 was not altered by various N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists. Because superoxide dismutase and catalase, which remove superoxide anion, decreased the augmented death of glucose-deprived immunostimulated CGC, the reaction of NO with superoxide to form peroxynitrite appears to be implicated in the potentiated neurotoxicity. Our data indicate that immunostimulated glial cells potentiate the death of glucose-deprived neurons 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.",
keywords = "Cerebellar granule cells (CGC), Glia, Ischemia, N-methyl-D-aspartate (NMDA), Neurotoxicity, Nitric oxide (NO)",
author = "Won-Ki Kim and Seo, {Dong Ook} and Choi, {Jung J.} and Ko, {Kwang H.}",
year = "1999",
month = "5",
day = "1",
language = "English",
volume = "16",
pages = "415--424",
journal = "Journal of Neurotrauma",
issn = "0897-7151",
publisher = "Mary Ann Liebert Inc.",
number = "5",

}

TY - JOUR

T1 - Immunostimulated glial cells potentiate glucose deprivation-induced death of cultured rat cerebellar granule cells

AU - Kim, Won-Ki

AU - Seo, Dong Ook

AU - Choi, Jung J.

AU - Ko, Kwang H.

PY - 1999/5/1

Y1 - 1999/5/1

N2 - The present study investigates whether immunostimulated glial expression of inducible nitric oxide synthase influences the glucose deprivation- induced death of rat cerebellar granule cells (CGC). CGC/glia cocultures were immunostimulated by interferon-γ (200 U/ml) and lipopolysaccharides (1 μg/ml) and 2 days later were challenged by glucose deprivation. Neurotoxicity was assessed by measuring the release of lactate dehydrogenase. Neither a 2-h glucose deprivation nor a 2-day immunostimulation altered the viability of CGC. A 2-day immunostimulation, however, markedly potentiated the glucose deprivation-induced death of CGC. The increased death of glucose- deprived CGC after immunostimulation was mimicked by the nitric oxide (NO) releasing reagent 3-morpholinosydnonimine (SIN-1) and was partially prevented by the NO synthase (NOS) inhibitor N(G)-nitroarginine. The increased death of glucose-deprived CGC either after immunostimulation or by SIN-1 was not altered by various N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists. Because superoxide dismutase and catalase, which remove superoxide anion, decreased the augmented death of glucose-deprived immunostimulated CGC, the reaction of NO with superoxide to form peroxynitrite appears to be implicated in the potentiated neurotoxicity. Our data indicate that immunostimulated glial cells potentiate the death of glucose-deprived neurons 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.

AB - The present study investigates whether immunostimulated glial expression of inducible nitric oxide synthase influences the glucose deprivation- induced death of rat cerebellar granule cells (CGC). CGC/glia cocultures were immunostimulated by interferon-γ (200 U/ml) and lipopolysaccharides (1 μg/ml) and 2 days later were challenged by glucose deprivation. Neurotoxicity was assessed by measuring the release of lactate dehydrogenase. Neither a 2-h glucose deprivation nor a 2-day immunostimulation altered the viability of CGC. A 2-day immunostimulation, however, markedly potentiated the glucose deprivation-induced death of CGC. The increased death of glucose- deprived CGC after immunostimulation was mimicked by the nitric oxide (NO) releasing reagent 3-morpholinosydnonimine (SIN-1) and was partially prevented by the NO synthase (NOS) inhibitor N(G)-nitroarginine. The increased death of glucose-deprived CGC either after immunostimulation or by SIN-1 was not altered by various N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists. Because superoxide dismutase and catalase, which remove superoxide anion, decreased the augmented death of glucose-deprived immunostimulated CGC, the reaction of NO with superoxide to form peroxynitrite appears to be implicated in the potentiated neurotoxicity. Our data indicate that immunostimulated glial cells potentiate the death of glucose-deprived neurons 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.

KW - Cerebellar granule cells (CGC)

KW - Glia

KW - Ischemia

KW - N-methyl-D-aspartate (NMDA)

KW - Neurotoxicity

KW - Nitric oxide (NO)

UR - http://www.scopus.com/inward/record.url?scp=0345189549&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0345189549&partnerID=8YFLogxK

M3 - Article

C2 - 10369561

AN - SCOPUS:0345189549

VL - 16

SP - 415

EP - 424

JO - Journal of Neurotrauma

JF - Journal of Neurotrauma

SN - 0897-7151

IS - 5

ER -