ArticleJournal of neuroinflammation2018
Glutaminase 1 regulates the release of extracellular vesicles during neuroinflammation through key metabolic intermediate alpha-ketoglutarate.
Article in Journal of neuroinflammation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 37 citations in OpenAlex.
- Targeting microglial glutaminase 1 protects against ferroptosis-driven cognitive impairment in perioperative neurocognitive disorders.Cell death and differentiation · 2026Article
- Exosomes in Amyloid Propagation-Roles in Neurodegeneration.Molecular neurobiology · 2026Review
- Neuroinflammation and NeuroHIV: understanding the role of HIV-1 related factors in microglial activation.Translational psychiatry · 2026Review
- NUFIP1 gain of function promotes fibrotic remodeling and reveals a ZNHIT3-linked metabolic vulnerability in idiopathic pulmonary fibrosis models.Frontiers in immunology · 2026Article
- Tuberculous meningitis alters the proteomic landscape of brain-derived extracellular vesicles.bioRxiv : the preprint server for biology · 2025Article
- Recent insights into the roles and therapeutic potentials of GLS1 in inflammatory diseases.Journal of pharmaceutical analysis · 2025Review
- Identification of glutamine as a potential therapeutic target in dry eye disease.Signal transduction and targeted therapy · 2025Article
- Ex-VivoJournal of proteome research · 2024Article
- Effect of General Anesthetic Agents on Microglia.Aging and disease · 2024Review
- Glutamine metabolic microenvironment drives M2 macrophage polarization to mediate trastuzumab resistance in HER2-positive gastric cancer.Cancer communications (London, England) · 2023Article
- Cuproptosis-a potential target for the treatment of osteoporosis.Frontiers in endocrinology · 2023Review
- Role of Ceramides and Lysosomes in Extracellular Vesicle Biogenesis, Cargo Sorting and Release.International journal of molecular sciences · 2022Review
- miR‑363‑3p attenuates the oxygen‑glucose deprivation/reoxygenation‑induced neuronal injuryMolecular medicine reports · 2022Article
- Mitochondrial dysfunction in microglia: a novel perspective for pathogenesis of Alzheimer's disease.Journal of neuroinflammation · 2022Review
- Glutamine antagonist JHU083 improves psychosocial behavior and sleep deficits in EcoHIV-infected mice.Brain, behavior, & immunity - health · 2022Article
- Comprehensive analysis of cuproptosis-related genes in immune infiltration in ischemic stroke.Frontiers in neurology · 2022Article
- The Regulatory Role ofMediators of inflammation · 2021Review
- Propofol Inhibits Microglial ActivationFrontiers in cellular neuroscience · 2021Article
- The Messenger Apps of the cell: Extracellular Vesicles as Regulatory Messengers of Microglial Function in the CNS.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Review
- Embryonic Heat Conditioning Induces TET-Dependent Cross-Tolerance to Hypothalamic Inflammation Later in Life.Frontiers in genetics · 2020Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundExtracellular vesicles (EVs) are important in the intercellular communication of the central nervous system, and their release is increased during neuroinflammation. Our previous data demonstrated an increased release of EVs during HIV-1 infection and immune activation in glial cells. However, the molecular mechanism by which infection and inflammation increase EV release remains unknown. In the current study, we investigated the role of glutaminase 1 (GLS1)-mediated glutaminolysis and the production of a key metabolic intermediate α-ketoglutarate on EV release.
methodsHuman monocyte-derived macrophage primary cultures and a BV2 microglia cell line were used to represent the innate immune cells in the CNS. Transmission electron microscopy, nanoparticle tracking analysis, and Western blots were used to determine the EV regulation. GLS1 overexpression was performed using an adenovirus vector in vitro and transgenic mouse models in vivo. Data were evaluated statistically by ANOVA, followed by the Bonferroni post-test for paired observations.
resultsOur data revealed an increased release of EVs in GLS1-overexpressing HeLa cells. In HIV-1-infected macrophages and immune-activated microglia BV2 cells, treatment with bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES) or CB839, two specific GLS inhibitors, significantly decreased EV release, suggesting a critical role of GLS1 in EV release. Furthermore, addition of α-ketoglutarate or ceramide rescued EV release during BPTES treatment, implicating α-ketoglutarate and ceramide as critical downstream effectors for GLS inhibitors. These findings were further corroborated with the investigation of brain tissues in GLS1-transgenic mice. The EV levels were significantly higher in GLS1 transgenic mice than those in control mice, suggesting that GLS1 increases EV release in vivo.
conclusionsThese findings suggest that GLS1-mediated glutaminolysis and its downstream production of α-ketoglutarate are essential in regulating EV release during HIV-1 infection and immune activation. These new mechanistic regulations may help understand how glutamine metabolism shapes EV biogenesis and release during neuroinflammation.
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