ArticleThe Journal of biological chemistry2016
Interleukin 1β Regulation of the System xc- Substrate-specific Subunit, xCT, in Primary Mouse Astrocytes Involves the RNA-binding Protein HuR.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- Orchestrating neuroinflammation: A symphony of Interleukin-1 and cell type-specific Interleukin-1 receptor type 1 signaling in the brain.Brain behavior and immunity integrative · 2026Article
- Neuron-Glia Crosstalk in the Regulation of Astrocytic Antioxidative Mechanisms Following CNS Injury.Antioxidants (Basel, Switzerland) · 2025Review
- Fluoride Exposure Increases the Activity of the Cystine/Glutamate Exchanger in Glia Cells.Neurochemical research · 2025Article
- Nrf2 Regulates Basal Glutathione Production in Astrocytes.International journal of molecular sciences · 2025Article
- System Xc-pathway as a potential regulatory target in neurological disorders.Frontiers in pharmacology · 2025Review
- RNA binding protein PUM2 promotes IL-1β-induced apoptosis of chondrocytes via regulating FOXO3 expression.Heliyon · 2024Article
- Decreased xCT activity in patients associated withFrontiers in pharmacology · 2022Article
- Validation of a System xFrontiers in cellular neuroscience · 2021Article
- Nutritional ketosis as an intervention to relieve astrogliosis: Possible therapeutic applications in the treatment of neurodegenerative and neuroprogressive disorders.European psychiatry : the journal of the Association of European Psychiatrists · 2020Review
- IL-1β induces rod degeneration through the disruption of retinal glutamate homeostasis.Journal of neuroinflammation · 2020Article
- Interleukin-1β Protects Neurons against Oxidant-Induced Injury via the Promotion of Astrocyte Glutathione Production.Antioxidants (Basel, Switzerland) · 2018Article
- Cysteine, Glutathione, and Thiol Redox Balance in Astrocytes.Antioxidants (Basel, Switzerland) · 2017Review
- Tumour-Derived Glutamate: Linking Aberrant Cancer Cell Metabolism to Peripheral Sensory Pain Pathways.Current neuropharmacology · 2017Article
- Redox-Related Epigenetic Mechanisms in Glioblastoma: Nuclear Factor (Erythroid-Derived 2)-Like 2, Cobalamin, and Dopamine Receptor Subtype 4.Frontiers in oncology · 2017Article
- Inhibiting STAT3 in a murine model of human breast cancer-induced bone pain delays the onset of nociception.Molecular painArticle
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4 authors at 1 institution in 1 country.
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Abstract
System xc(-) is a heteromeric amino acid cystine/glutamate antiporter that is constitutively expressed by cells of the CNS, where it functions in the maintenance of intracellular glutathione and extracellular glutamate levels. We recently determined that the cytokine, IL-1β, increases the activity of system xc(-) in CNS astrocytes secondary to an up-regulation of its substrate-specific light chain, xCT, and that this occurs, in part, at the level of transcription. However, an in silico analysis of the murine xCT 3'-UTR identified numerous copies of adenine- and uridine-rich elements, raising the possibility that undefined trans-acting factors governing mRNA stability and translation may also contribute to xCT expression. Here we show that IL-1β increases the level of mRNA encoding xCT in primary cultures of astrocytes isolated from mouse cortex in association with an increase in xCT mRNA half-life. Additionally, IL-1β induces HuR translocation from the nucleus to the cytoplasm. RNA immunoprecipitation analysis reveals that HuR binds directly to the 3'-UTR of xCT in an IL-1β-dependent manner. Knockdown of endogenous HuR protein abrogates the IL-1β-mediated increase in xCT mRNA half-life, whereas overexpression of HuR in unstimulated primary mouse astrocytes doubles the half-life of constitutive xCT mRNA. This latter effect is accompanied by an increase in xCT protein levels, as well as a functional increase in system xc(-) activity. Altogether, these data support a critical role for HuR in mediating the IL-1β-induced stabilization of astrocyte xCT mRNA.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.