Cited by 181Neuroscience and Neuropharmacology ResearchAmino Acid Enzymes and MetabolismNeuroinflammation and Neurodegeneration Mechanisms

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

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Zou, Jian, Wang, Yan-Xia, Dou, Fang-Fang, Lü, He-Zuo, Ma, Zheng-Wen, Lu, Pei-Hua, Xu, Xiao-Ming·2010·Neurochemistry International

DOI 10.1016/j.neuint.2009.12.021PMC PMC2831119

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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-alpha (TNF-alpha) 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.

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Authors: Zou, J., Wang, Y.-X., Dou, F.-F., Lü, H.-Z., Ma, Z.-W., Lu, P.-H., & Xu, X.-M.
Affiliations: Shanghai Jiao Tong University (CN)
Corresponding author: Lu, Pei-Hua
Xu, Xiao-Ming
ORCID: Zou, Jian
Lü, He-Zuo
Lu, Pei-Hua
Xu, Xiao-Ming
Venue: Neurochemistry International
Publisher: Elsevier BV
Published: 2010-03
Volume: 56
Issue: 4
Pages: 577-584
ISSN: 0197-0186 (ISSN-L)
DOI: 10.1016/j.neuint.2009.12.021
PMC: PMC2831119
OpenAlex: W2070004275
Cited by: 181
References: 47
Citations by year: 2026: 10 · 2025: 8 · 2024: 8 · 2023: 10 · 2022: 8 · 2021: 10 · 2020: 16 · 2019: 10 · 2018: 9 · 2017: 11 · 2016: 16 · 2015: 14 · 2014: 12 · 2013: 16 · 2012: 9
FWCI: 5.04
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neurochemistry International (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
IUScholarWorks (Indiana University) (submittedVersion)
Funders: National Institutes of Health (7r01ns050243-06)
National Institute of Neurological Disorders and Stroke (R01NS111776, NS52290, R01NS059622, R01NS052290, R01-NS050243, R01NS036350, NS36350, NS50243)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: glutamine synthetase, astrocytes, glutamate excitotoxicity, glutamate uptake, glutamine release, glutamate transporters, glutamate clearance, TNF-α, neuroprotection, gene transfer, neuronal cell death
MeSH terms: Animals, Astrocytes, Cell Survival, Cells, Cultured, Glutamate-Ammonia Ligase, Nerve Degeneration, Neurons, Plasmids, Transfection, Tumor Necrosis Factor-alpha, Blotting, Western, Down-Regulation, Rats, Sprague-Dawley, Apoptosis, Glutamic Acid, Excitatory Amino Acids, Rats

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

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