Involvement of K v1.3 and p38 MAPK signaling in HIV-1 glycoprotein 120-induced microglia neurotoxicity

J. Liu, C. Xu, L. Chen, P. Xu, Huangui Xiong

Research output: Contribution to journalArticle

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Abstract

Inflammatory responses mediated by activated microglia play a pivotal role in the pathogenesis of human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders. Studies on identification of specific targets to control microglia activation and resultant neurotoxic activity are imperative. Increasing evidence indicate that voltage-gated K + (K v) channels are involved in the regulation of microglia functionality. In this study, we investigated K v1.3 channels in the regulation of neurotoxic activity mediated by HIV-1 glycoprotein 120 (gp120)-stimulated rat microglia. Our results showed treatment of microglia with gp120 increased the expression levels of K v1.3 mRNA and protein. In parallel, whole-cell patch-clamp studies revealed that gp120 enhanced microglia K v1.3 current, which was blocked by margatoxin, a K v1.3 blocker. The association of gp120 enhancement of K v1.3 current with microglia neurotoxicity was demonstrated by experimental results that blocking microglia K v1.3 attenuated gp120-associated microglia production of neurotoxins and neurotoxicity. Knockdown of K v1.3 gene by transfection of microglia with K v1.3-siRNA abrogated gp120-associated microglia neurotoxic activity. Further investigation unraveled an involvement of p38 MAPK in gp120 enhancement of microglia K v1.3 expression and resultant neurotoxic activity. These results suggest not only a role K v1.3 may have in gp120-associated microglia neurotoxic activity, but also a potential target for the development of therapeutic strategies.

Original languageEnglish (US)
Article numbere254
JournalCell Death and Disease
Volume3
Issue number1
DOIs
StatePublished - Jan 1 2012

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Keywords

  • Cytokines
  • HIV-1gp120
  • Microglia
  • Neurotoxicity
  • Voltage-gated K channels

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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