Glutamine synthetase down-regulation reduces astrocyte protection against glutamate excitotoxicity to neurons

Jian Zou, Yan Xia Wang, Fang Fang Dou, He Zuo Lü, Zheng Wen Ma, Pei Hua Lu, Xiao Ming Xu

Research output: Contribution to journalArticle

101 Scopus citations

Abstract

Although the role of astrocyte glutamate transporters in glutamate clearance is well illustrated, the role of glutamine synthetase (GS) that influences this process remains to be elucidated. We examined whether GS affected the uptake of glutamate in astrocytes in vitro. The glutamate uptake was assessed by measuring the concentration of glutamate and glutamine in culture medium in the presence or absence of glutamate. We demonstrated that inhibition of GS in astrocytes by MSO significantly impaired glutamate uptake and glutamine release. Conversely, induction of GS expression in astrocytes by gene transfer significantly enhanced the glutamate uptake and glutamine release. When an inflammatory cytokine tumor necrosis factor-α (TNF-α) was applied to the cultures, it significantly reduced GS expression and inhibited glutamate-induced GS activation resulting in increased excitotoxicity to neurons. These results suggest that GS in astrocytes may represent a novel target for neuroprotection against neuronal dysfunction and death that occur in many neurological disorders.

Original languageEnglish (US)
Pages (from-to)577-584
Number of pages8
JournalNeurochemistry International
Volume56
Issue number4
DOIs
StatePublished - Mar 1 2010

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Keywords

  • Astrocyte
  • Glutamate
  • Glutamate uptake
  • Glutamine
  • Glutamine synthetase
  • Neuroexcitotoxicity
  • TNF-α

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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