ArticleMolecular neurodegeneration2015
Glutaminase-containing microvesicles from HIV-1-infected macrophages and immune-activated microglia induce neurotoxicity.
Article in Molecular neurodegeneration, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Metabolic Reprogramming of Microglia in Neuroinflammation and Depression.International journal of molecular sciences · 2026Review
- Tuberculous meningitis alters the proteomic landscape of brain-derived extracellular vesicles.bioRxiv : the preprint server for biology · 2025Article
- Immune-Related Protein and Non-Coding RNA Cargo of Extracellular Vesicles Participate in the Chronic Inflammation Induced by HIV Infection.Journal of extracellular biology · 2025Article
- Ceramide-mediated orchestration of oxidative stress response through filopodia-derived small extracellular vesicles.Journal of extracellular vesicles · 2024Article
- KYNA Ameliorates Glutamate Toxicity of HAND by Enhancing Glutamate Uptake in A2 Astrocytes.International journal of molecular sciences · 2024Article
- Glutamine metabolic microenvironment drives M2 macrophage polarization to mediate trastuzumab resistance in HER2-positive gastric cancer.Cancer communications (London, England) · 2023Article
- Cathepsin L-containing exosomes from α-synuclein-activated microglia induce neurotoxicity through the P2X7 receptor.NPJ Parkinson's disease · 2022Article
- Glutamine antagonist JHU083 improves psychosocial behavior and sleep deficits in EcoHIV-infected mice.Brain, behavior, & immunity - health · 2022Article
- Suppression of HIV-associated Macrophage Activation by a p75 Neurotrophin Receptor Ligand.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2022Article
- Extracellular vesicles derived from glioblastoma promote proliferation and migration of neural progenitor cells via PI3K-Akt pathway.Cell communication and signaling : CCS · 2022Article
- Extracellular Microvesicles Released From Brain Endothelial Cells are Detected in Animal Models Of HIV-1 Signifying Unresolved Inflammation.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Article
- Review
- Extracellular Vesicles as an Emerging Frontier in Spinal Cord Injury Pathobiology and Therapy.Trends in neurosciences · 2021Review
- Ceramide and Related Molecules in Viral Infections.International journal of molecular sciences · 2021Review
- Emerging roles of extracellular vesicles in mediating RNA virus infection.Fundamental research · 2021Review
- The versatile role of exosomes in human retroviral infections: from immunopathogenesis to clinical application.Cell & bioscience · 2021Review
- Extracellular Vesicles as a Means of Viral Immune Evasion, CNS Invasion, and Glia-Induced Neurodegeneration.Frontiers in cellular neuroscience · 2021Article
- Recent cannabis use in HIV is associated with reduced inflammatory markers in CSF and blood.Neurology(R) neuroimmunology & neuroinflammation · 2020Observational
- The Glutamate System as a Crucial Regulator of CNS Toxicity and Survival of HIV Reservoirs.Frontiers in cellular and infection microbiology · 2020Review
- Dendrimer-conjugated glutaminase inhibitor selectively targets microglial glutaminase in a mouse model of Rett syndrome.Theranostics · 2020Article
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Authors and funding
8 authors.
Funding
Abstract
backgroundHIV-1-infected and/or immune-activated microglia and macrophages are pivotal in the pathogenesis of HIV-1-associated neurocognitive disorders (HAND). Glutaminase, a metabolic enzyme that facilitates glutamate generation, is upregulated and may play a pathogenic role in HAND. Our previous studies have demonstrated that glutaminase is released to the extracellular fluid during HIV-1 infection and neuroinflammation. However, key molecular mechanisms that regulate glutaminase release remain unknown. Recent advances in understanding intercellular trafficking have identified microvesicles (MVs) as a novel means of shedding cellular contents. We posit that during HIV-1 infection and immune activation, microvesicles may mediate glutaminase release, generating excessive and neurotoxic levels of glutamate.
resultsMVs isolated through differential centrifugation from cell-free supernatants of monocyte-derived macrophages (MDM) and BV2 microglia cell lines were first confirmed in electron microscopy and immunoblotting. As expected, we found elevated number of MVs, glutaminase immunoreactivities, as well as glutaminase enzyme activity in the supernatants of HIV-1 infected MDM and lipopolysaccharide (LPS)-activated microglia when compared with controls. The elevated glutaminase was blocked by GW4869, a neutral sphingomyelinase inhibitor known to inhibit MVs release, suggesting a critical role of MVs in mediating glutaminase release. More importantly, MVs from HIV-1-infected MDM and LPS-activated microglia induced significant neuronal injury in rat cortical neuron cultures. The MV neurotoxicity was blocked by a glutaminase inhibitor or GW4869, suggesting that the neurotoxic potential of HIV-1-infected MDM and LPS-activated microglia is dependent on the glutaminase-containing MVs.
conclusionsThese findings support MVs as a potential pathway/mechanism of excessive glutamate generation and neurotoxicity in HAND and therefore MVs may serve as a novel therapeutic target.
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