HIV decreases glutamate transport in SK-N-MC neuroblastoma cells

Todd C. Pappas, Sudar Alagarsamy, Richard B Pollard, Mostafa Nokta

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Autopsy studies of patients with AIDS dementia have shown neuronal loss consistent with a neurotoxic component of this disease. In vitro studies suggest that viral products or cytokines from HIV-infected macrophages (Mφ) may modulate or directly mediate excitotoxic cell death of neurons. Mφ differentiated from peripheral mononuclear blood cultures were infected with HIV, and conditioned media (CM) were harvested from these cultures. Exposure of SK-N-MC (neuroblastoma) cells to CM from HIV-infected Mφ for 4, 24 or ≤ 48 h resulted in a mean suppression of 12-34% of the glutamate transport V(max) with no appreciable change in transport K(m). An astrocytoma tumor cell, U373MG, showed similar CM-mediated glutamate uptake suppression. Changes were evident in total and Na+-dependent glutamate uptake, with significantly more suppression of Na+-dependent uptake. Similar effects were seen with the non-metabolizable transporter agonist D-aspartate, indicating that the effect was on transport and not metabolism. No suppression was seen with CM from uninfected Mφ or Mφ infected with heat-inactivated HIV. The magnitude of uptake suppression was not correlated with CM p24 values, and removal of CM virions by ultracentrifugation and immunoprecipitation did not alter the uptake-suppressive properteis of infected Mφ CM. Uptake suppression was seen when Mφ were infected with Mφ-tropic strains HIV(SF162), HIV(JR-CSF), HIV(NFN-SX) and a Mφ-tropic patient isolate, but not lymphotropic strain HIV(LAI). HIV-infected Mφ may produce substances which suppress neuronal and glial glutamate neurotransmitter uptake, resulting in higher extracellular glutamate levels and leading possibly to deficits in cell signaling and neurotoxicity.

Original languageEnglish (US)
Pages (from-to)69-79
Number of pages11
JournalJournal of NeuroVirology
Volume4
Issue number1
StatePublished - Feb 1998
Externally publishedYes

Keywords

  • AIDS dementia
  • Glutamate transport
  • Human immunodeficiency virus
  • Macrophage
  • Neuron

ASJC Scopus subject areas

  • Virology
  • Clinical Neurology

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