ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2007
System x(c)- activity and astrocytes are necessary for interleukin-1 beta-mediated hypoxic neuronal injury.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 111 citations in OpenAlex.
- Plasma Cystine as a Marker of Acute Stroke Severity.Diagnostics (Basel, Switzerland) · 2025Article
- Arsenite-Mediated Transcriptional Regulation of Glutathione Synthesis in Mammalian Primary Cortical Astrocytes.International journal of molecular sciences · 2025Article
- Sulfide regulation and catabolism in health and disease.Signal transduction and targeted therapy · 2025Review
- Design, synthesis, and characterization of novel system xJournal of neuroinflammation · 2023Article
- Iron Saturation Drives Lactoferrin Effects on Oxidative Stress and Neurotoxicity Induced by HIV-1 Tat.International journal of molecular sciences · 2023Article
- The mitochondrial associated endoplasmic reticulum membranes: A platform for the pathogenesis of inflammation-mediated metabolic diseases.Immunity, inflammation and disease · 2022Review
- Autism Spectrum Disorder: Focus on Glutamatergic Neurotransmission.International journal of molecular sciences · 2022Review
- Article
- Glutamatergic system components as potential biomarkers and therapeutic targets in cancer in non-neural organs.Frontiers in endocrinology · 2022Review
- The Cystine/Glutamate Antiporter, System xFrontiers in cellular neuroscience · 2022Article
- Amyloid-β 25-35 Induces Neurotoxicity through the Up-Regulation of Astrocytic System XAntioxidants (Basel, Switzerland) · 2021Article
- Influence of glutamate and GABA transport on brain excitatory/inhibitory balance.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- xCT/SLC7A11 antiporter function inhibits HIV-1 infection.Virology · 2021Article
- Validation of a System xFrontiers in cellular neuroscience · 2021Article
- The Chemical Biology of Ferroptosis in the Central Nervous System.Cell chemical biology · 2020Review
- IL-1β induces rod degeneration through the disruption of retinal glutamate homeostasis.Journal of neuroinflammation · 2020Article
- The Glutamate System as a Crucial Regulator of CNS Toxicity and Survival of HIV Reservoirs.Frontiers in cellular and infection microbiology · 2020Review
- Nrf2-Mediated System xMolecular neurobiology · 2019Article
- Investigating the role of interleukin-1 beta and glutamate in inflammatory bowel disease and epilepsy using discovery browsing.Journal of biomedical semantics · 2018Article
- Depression following a traumatic brain injury: uncovering cytokine dysregulation as a pathogenic mechanism.Neural regeneration research · 2018Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The purpose of this study was to elucidate the cellular/biochemical pathway(s) by which interleukin-1beta (IL-1beta) contributes to the pathogenesis of hypoxic-ischemic brain damage. In vivo, IL-1 receptor type I (IL-1RI)-deficient mice showed smaller infarcts and less neurological deficits than wild-type animals after a 90 min reversible middle cerebral artery occlusion. In vitro, IL-1beta mediated an enhancement of hypoxic neuronal injury in murine cortical cultures that was lacking in cultures derived from IL-1RI null mutant animals and was blocked by the IL-1 receptor antagonist or an IL-1RI blocking antibody. This IL-1beta-mediated potentiation of hypoxic neuronal injury was associated with an increase in both cellular cystine uptake ([cystine]i) and extracellular glutamate levels ([glutamate]e) and was prevented by either ionotropic glutamate receptor antagonism or removal of L-cystine, suggesting a role for the cystine/glutamate antiporter (System x(c)-). Indeed, dual System x(c)-/metabotropic glutamate receptor subunit 1 (mGluR1) antagonism but not selective mGluR1 antagonism prevented neuronal injury. Additionally, cultures derived from mGluR1-deficient mice exhibited the same potentiation in injury after treatment with IL-1beta as wild-type cultures, an effect prevented by System x(c)-/mGluR1 antagonism. Finally, assessment of System x(c)- function and kinetics in IL-1beta-treated cultures revealed an increase in velocity of cystine transport (Vmax), in the absence of a change in affinity (Km). Neither the enhancement in [cystine]i, [glutamate]e, or neuronal injury were observed in chimeric cultures consisting of IL-1RI(+/+) neurons plated on top of IL-1RI(-/-) astrocytes, highlighting the importance of astrocyte-mediated alterations in System x(c)- as a novel contributor to the development and progression of hypoxic neuronal injury.
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Registered trials
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.