Enhanced proteolysis of IκBα and IκBβ proteins in astrocytes by Moloney murine leukemia virus (MoMuLV)-ts1 infection: A potential mechanism of NF-κB activation

H. T. Kim, W. Qiang, P. K Y Wong, G. Stoica*

*Corresponding author for this work

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Moloney murine leukemia virus (MoMuLV)-ts1-mediated neuronal degeneration in mice is likely due to loss of glial support and release of inflammatory cytokines and neurotoxins from surrounding ts1-infected glial cells including astrocytes. NF-κB is a transcription factor that participates in the transcriptional activation of a variety of immune and inflammatory genes. We investigated whether ts1 activates NF-κB in astrocytes and examined the mechanism(s) responsible for the activation of NF-κB by ts1 infection in vitro. Here we present evidence that ts1 infection of astrocytes in vitro activates NF-κB by enhanced proteolysis of the NF-κB inhibitors, IκBα and IκBβ. In in vitro studies using protease inhibitors, IκBα proteolysis in ts1-infected astrocytes was significantly blocked by a specific calpain inhibitor calpeptin but not by MG-132, a specific proteasome inhibitor, whereas rapid IκBβ proteolysis was blocked by MG-132. Furthermore, treatment with MG-132 increased levels of multi-ubiquitinated IκBβ protein in ts 1-infected astrocytes. These results indicate that the calpain proteolysis is a major mechanism of IκBα proteolysis in ts1-infected astrocytes. Additionally, ts1 infection of astrocytes in vitro increased expression of inducible nitric oxide synthase (iNOS), a NF-κB-dependent gene product. Our results suggest that NF-κB activation in ts1-infected astrocytes is mediated by enhanced proteolysis of IκBα and IκBβ through two different proteolytic pathways, the calpain and ubiquitin-proteasome pathways, resulting in increased expression of iNOS, a NF-κB-dependent gene.

Original languageEnglish (US)
Pages (from-to)466-475
Number of pages10
JournalJournal of neurovirology
Volume7
Issue number5
DOIs
StatePublished - 2001

Keywords

  • Astrocytes
  • IκB
  • MoMuLV-ts1
  • NF-κB
  • iNOS

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

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