TNF-α promotes extracellular vesicle release in mouse astrocytes through glutaminase

Kaizhe Wang, Ling Ye, Hongfang Lu, Huili Chen, Yanyan Zhang, Yunlong Huang, Jialin C. Zheng

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Background: Extracellular vesicles (EVs) are membrane-contained vesicles shed from cells. EVs contain proteins, lipids, and nucleotides, all of which play important roles in intercellular communication. The release of EVs is known to increase during neuroinflammation. Glutaminase, a mitochondrial enzyme that converts glutamine to glutamate, has been implicated in the biogenesis of EVs. We have previously demonstrated that TNF-α promotes glutaminase expression in neurons. However, the expression and the functionality of glutaminase in astrocytes during neuroinflammation remain unknown. We posit that TNF-α can promote the release of EVs in astrocytes through upregulation of glutaminase expression. Results: Release of EVs, which was demonstrated by electron microscopy, nanoparticle tracking analysis (NTA), and Western Blot, increased in mouse astrocytes when treated with TNF-α. Furthermore, TNF-α treatment significantly upregulated protein levels of glutaminase and increased the production of glutamate, suggesting that glutaminase activity is increased after TNF-α treatment. Interestingly, pretreatment with a glutaminase inhibitor blocked TNF-α-mediated generation of reactive oxygen species in astrocytes, which indicates that glutaminase activity contributes to stress in astrocytes during neuroinflammation. TNF-α-mediated increased release of EVs can be blocked by either the glutaminase inhibitor, antioxidant N-acetyl-l-cysteine, or genetic knockout of glutaminase, suggesting that glutaminase plays an important role in astrocyte EV release during neuroinflammation. Conclusions: These findings suggest that glutaminase is an important metabolic factor controlling EV release from astrocytes during neuroinflammation.

Original languageEnglish (US)
Article number87
JournalJournal of Neuroinflammation
Volume14
Issue number1
DOIs
StatePublished - Apr 20 2017

Keywords

  • Astrocytes
  • Extracellular vesicles
  • Glutaminase
  • TNF-α

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

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