ArticleJournal of neuroinflammation2022
Lactate attenuates astrocytic inflammation by inhibiting ubiquitination and degradation of NDRG2 under oxygen-glucose deprivation conditions.
Article in Journal of neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 44 citations in OpenAlex.
- Apoptotic body-encapsulated nanoparticles regulate inflammation through macrophage polarization mediated by lactic acid.Annals of medicine · 2026Article
- Central neural circuits and their associated mechanisms of inter-organ crosstalk.Frontiers in cell and developmental biology · 2026Review
- Dual roles of lactate and lactylation modification in the nervous system: neuroprotection and neuroinjury.Frontiers in aging neuroscience · 2026Review
- Beyond Fuel: Exercise-Induced Lactate as a Metabolic-Epigenetic Regulator in Central Nervous System Health and Disease.Biomolecules · 2025Review
- Single-cell and spatial transcriptomics reveal lactylation-associated tumor cell clusters and define a prognostic risk model in glioblastoma.BMC cancer · 2025Article
- Extracellular lactate improves neurogenesis by modulating H3K9 lactylation and SnoN expression under hypoxic conditions.Stem cell research & therapy · 2025Article
- Review
- Regulation of L-Lactate in Glutamate Excitotoxicity Under Cerebral Ischemia: Pathophysiology and Preventive Strategy.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The role of protein lactylation in brain health and disease: current advances and future directions.Cell death discovery · 2025Review
- Transcriptomics, single-cell sequencing and spatial sequencing-based studies of cerebral ischemia.European journal of medical research · 2025Review
- Reactive Astrocytes in Glioma: Emerging Opportunities and Challenges.International journal of molecular sciences · 2025Review
- L- and D-Lactate: unveiling their hidden functions in disease and health.Cell communication and signaling : CCS · 2025Review
- Usp18 Mediates D-Dopachrome Tautomerase-Induced Astrocytic Inflammation After Spinal Cord Injury.Journal of inflammation research · 2025Article
- Global maintenance of histone post-translational modifications during the transition into anoxia in embryos of the annual killifishEnvironmental epigenetics · 2025Article
- Dynamic Neuro-Glial-Vascular Responses in a Mouse Model of Vascular Cognitive Impairment.Neuroglia (Basel, Switzerland) · 2024Article
- KDM2B regulates stroke injury by modulating OGT-mediated 0-GlcNAcylation of SLC7A11.Communications biology · 2024Article
- The Roles of Non-coding RNA Targeting Astrocytes in Cerebral Ischemia.Molecular neurobiology · 2024Review
- Lactylation of histone by BRD4 regulates astrocyte polarization after experimental subarachnoid hemorrhage.Journal of neuroinflammation · 2024Article
- METTL3 regulates TFRC ubiquitination and ferroptosis through stabilizing NEDD4L mRNA to impact stroke.Cell biology and toxicology · 2024Article
- Role of hypoxic exosomes and the mechanisms of exosome release in the CNS under hypoxic conditions.Frontiers in neurology · 2023Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBrain lactate concentrations are enhanced in response to cerebral ischemia and promote the formation of reactive astrocytes, which are major components of the neuroinflammatory response and functional recovery, following cerebral ischemia. NDRG2 is upregulated during reactive astrocyte formation. However, its regulation and function are unclear. We studied the relationship between lactate and NDRG2 in astrocytes under conditions of ischemia or oxygen-glucose deprivation (OGD).
methodsWe examined astrocytic NDRG2 expression after middle cerebral artery occlusion (MCAO) using western blot and immunofluorescence staining. Under hypoxia conditions, we added exogenous L-lactate sodium (lactate) to cultured primary astrocytes to explore the effects of lactate on the ubiquitination modification of NDRG2. We profiled the transcriptomic features of NDRG2 silencing in astrocytes after 8 h of OGD conditions as well as exogenous lactate treatment by performing RNA-seq. Finally, we evaluated the molecular mechanisms of NDRG2 in regulating TNFα under OGD conditions using western blot and immunohistochemistry.
resultsReactive astrocytes strongly expressed NDRG2 in a rat model of MCAO. We also showed that lactate stabilizes astrocytic NDRG2 by inhibiting its ubiquitination. NDRG2 inhibition in astrocytes increased inflammation and upregulated immune-associated genes and signaling pathways. NDRG2 knockdown induced TNFα expression and secretion via c-Jun phosphorylation.
conclusionsWe revealed that under OGD conditions, lactate plays an important anti-inflammatory role and inhibits TNFα expression by stabilizing NDRG2, which is beneficial for neurological functional recovery. NDRG2 may be a new therapeutic target for cerebral ischemia.
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