Long-term modulation of glucose utilization by IL-1α and TNF-α in astrocytes: Na + pump activity as a potential target via distinct signaling mechanisms

Céline Véga, Luc Pellerin*, Robert Dantzer, Pierre Magistretti

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Interleukin-1α (IL-1α) and tumor necrosis factor-α (TNF-α) markedly stimulate glucose utilization in primary cultures of mouse cortical astrocytes. The mechanism that gives rise to this effect, which takes place several hours after application of cytokine, has remained unclear. Experiments were conducted to identify the major signaling cascades involved in the metabolic action of cytokine. First, the selective IL-1 receptor antagonist (IL-1ra) prevents the effect of IL-1α on glucose utilization in a concentration-dependent manner, whereas it has no effect on the action of TNF-α. Then, using inhibitors of three classical signaling cascades known to be activated by cytokines, it appears that the PI3 kinase is essential for the effect of both IL-1α and TNF-α, whereas the action of IL-1α also requires activation of the MAP kinase pathway. Participation of a phospholipase C-dependent pathway does not appear critical for both IL-1α and TNF-α. Inhibition of NO synthase by L-NAME did not prevent the metabolic response to both IL-1α and TNF-α, indicating that nitric oxide is probably not involved. In contrast, the Na + /K + ATPase inhibitor ouabain prevents the IL-1α and TNF-αstimulated 2-deoxyglucose (2DG) uptake. When treatment of astrocytes with a cytokine was followed 24 h later by an acute application of glutamate, a synergistic enhancement in glucose utilization was observed. This effect was greatly reduced by ouabain. These data suggest that Na + pump activity is a common target for both the long-term metabolic action of cytokines promoted by the activation of distinct signaling pathways and the enhanced metabolic response to glutamate.

Original languageEnglish (US)
Pages (from-to)10-18
Number of pages9
JournalGLIA
Volume39
Issue number1
DOIs
StatePublished - Jul 1 2002

Keywords

  • Cytokine
  • Glutamate
  • MAP kinase
  • Na /K ATPase
  • PI3 kinase
  • Phospholipase C

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

Fingerprint

Dive into the research topics of 'Long-term modulation of glucose utilization by IL-1α and TNF-α in astrocytes: Na <sup>+</sup> pump activity as a potential target via distinct signaling mechanisms'. Together they form a unique fingerprint.

Cite this