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

90 Citations (Scopus)

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

Fingerprint

Glutamate-Ammonia Ligase
Astrocytes
Glutamic Acid
Down-Regulation
Neurons
Glutamine
Amino Acid Transport System X-AG
Nervous System Diseases
Culture Media
Tumor Necrosis Factor-alpha
Cytokines

Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Glutamine synthetase down-regulation reduces astrocyte protection against glutamate excitotoxicity to neurons. / Zou, Jian; Wang, Yan Xia; Dou, Fang Fang; Lü, He Zuo; Ma, Zheng Wen; Lu, Pei Hua; Xu, Xiao-Ming.

In: Neurochemistry International, Vol. 56, No. 4, 03.2010, p. 577-584.

Research output: Contribution to journalArticle

Zou, Jian ; Wang, Yan Xia ; Dou, Fang Fang ; Lü, He Zuo ; Ma, Zheng Wen ; Lu, Pei Hua ; Xu, Xiao-Ming. / Glutamine synthetase down-regulation reduces astrocyte protection against glutamate excitotoxicity to neurons. In: Neurochemistry International. 2010 ; Vol. 56, No. 4. pp. 577-584.
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