Dataset Information

TNF-? promotes extracellular vesicle release in mouse astrocytes through glutaminase.

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-? promotes glutaminase expression in neurons. However, the expression and the functionality of glutaminase in astrocytes during neuroinflammation remain unknown. We posit that TNF-? 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-?. Furthermore, TNF-? treatment significantly upregulated protein levels of glutaminase and increased the production of glutamate, suggesting that glutaminase activity is increased after TNF-? treatment. Interestingly, pretreatment with a glutaminase inhibitor blocked TNF-?-mediated generation of reactive oxygen species in astrocytes, which indicates that glutaminase activity contributes to stress in astrocytes during neuroinflammation. TNF-?-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.

SUBMITTER: Wang K

PROVIDER: S-EPMC5399318 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Wang Kaizhe K Ye Ling L Lu Hongfang H Chen Huili H Zhang Yanyan Y Huang Yunlong Y Zheng Jialin C JC

Journal of neuroinflammation 20170420 1

<h4>Background</h4>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 expr ...[more]

PMID: 28427419

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