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The indolocarbazole Gö6976 protects neurons from lipopolysaccharide/interferon-gamma-induced cytotoxicity in murine neuron/glia co-cultures.

Publication ,  Journal Article
Jeohn, GH; Wilson, B; Wetsel, WC; Hong, JS
Published in: Brain Res Mol Brain Res
June 23, 2000

The expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO) after exposure to endotoxins has been implicated in immune-mediated neurotoxicity. The indolocarbazole compound Gö6976, which has been described as a selective protein kinase C (PKC) inhibitor in vitro, rescued neurons from lipopolysaccharide/interferon-gamma (LPS/IFNgamma)- or interleukin-1alpha/tumor necrosis alpha/IFNgamma (IL-1alpha/TNFalpha/IFNgamma)-induced cytotoxicity in murine primary neuron-glia co-cultures. Other compounds known to inhibit PKC, Ro31-8220, GF109203X, Gö7874, H7, staurosporine and H89, failed to rescue neurons from the LPS/IFNgamma-induced cytotoxicity. These results suggest that the neuroprotection by Gö6976 from the LPS/IFNgamma-induced neuronal cell death is not mediated through its reputed effects on PKC activity. The neuroprotection paralleled the inhibition of iNOS gene expression and NO production. However, further analyses correlating NO production with the extent of neurotoxicity suggested that additional mechanism(s) besides the inhibition of the iNOS/NO system may be responsible for the neuroprotective effects of Gö6976. An understanding of the mechanism underlying the neuroprotective effect of Gö6976 may provide key insights into potential interventions for immune-mediated neurodegenerative diseases.

Duke Scholars

Published In

Brain Res Mol Brain Res

DOI

ISSN

0169-328X

Publication Date

June 23, 2000

Volume

79

Issue

1-2

Start / End Page

32 / 44

Location

Netherlands

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Tetradecanoylphorbol Acetate
  • Reverse Transcriptase Polymerase Chain Reaction
  • Recombinant Proteins
  • Protein Kinase C
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase
  • Neuroprotective Agents
  • Neurons
  • Neurology & Neurosurgery
 

Citation

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ICMJE
MLA
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Jeohn, G. H., Wilson, B., Wetsel, W. C., & Hong, J. S. (2000). The indolocarbazole Gö6976 protects neurons from lipopolysaccharide/interferon-gamma-induced cytotoxicity in murine neuron/glia co-cultures. Brain Res Mol Brain Res, 79(1–2), 32–44. https://doi.org/10.1016/s0169-328x(00)00082-6
Jeohn, G. H., B. Wilson, W. C. Wetsel, and J. S. Hong. “The indolocarbazole Gö6976 protects neurons from lipopolysaccharide/interferon-gamma-induced cytotoxicity in murine neuron/glia co-cultures.Brain Res Mol Brain Res 79, no. 1–2 (June 23, 2000): 32–44. https://doi.org/10.1016/s0169-328x(00)00082-6.
Jeohn GH, Wilson B, Wetsel WC, Hong JS. The indolocarbazole Gö6976 protects neurons from lipopolysaccharide/interferon-gamma-induced cytotoxicity in murine neuron/glia co-cultures. Brain Res Mol Brain Res. 2000 Jun 23;79(1–2):32–44.
Jeohn, G. H., et al. “The indolocarbazole Gö6976 protects neurons from lipopolysaccharide/interferon-gamma-induced cytotoxicity in murine neuron/glia co-cultures.Brain Res Mol Brain Res, vol. 79, no. 1–2, June 2000, pp. 32–44. Pubmed, doi:10.1016/s0169-328x(00)00082-6.
Jeohn GH, Wilson B, Wetsel WC, Hong JS. The indolocarbazole Gö6976 protects neurons from lipopolysaccharide/interferon-gamma-induced cytotoxicity in murine neuron/glia co-cultures. Brain Res Mol Brain Res. 2000 Jun 23;79(1–2):32–44.
Journal cover image

Published In

Brain Res Mol Brain Res

DOI

ISSN

0169-328X

Publication Date

June 23, 2000

Volume

79

Issue

1-2

Start / End Page

32 / 44

Location

Netherlands

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Tetradecanoylphorbol Acetate
  • Reverse Transcriptase Polymerase Chain Reaction
  • Recombinant Proteins
  • Protein Kinase C
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase
  • Neuroprotective Agents
  • Neurons
  • Neurology & Neurosurgery