ArticleNeurochemistry international2014
Role of glutamate transporters in redox homeostasis of the brain.
Article in Neurochemistry international, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 52 citations in OpenAlex.
- Environmental Factors Drive Neurodegenerative Diseases Through Glutamate Excitotoxicity: A Convergent Mechanistic Pathway.Neuroscience bulletin · 2026Review
- Peroxisomal activity drives aggressive bladder cancer phenotypes and reveals erythorbic acid as a potential therapeutic modulator.Frontiers in oncology · 2026Article
- Ferroptosis in Diabetic Cardiomyopathy and Atherosclerosis: Mechanisms and Clinical Prospects.International journal of molecular sciences · 2025Review
- Proteomic Study Between Interstitial Channels Along Meridians and Adjacent Areas in Mini-Pigs.Biomolecules · 2025Article
- An investigation into the mechanism for Kaempferol improving melanocyte death based on network Pharmacology and experimental verification.Scientific reports · 2025Article
- Disrupted glutamate homeostasis as a target for glioma therapy.Pharmacological reports : PR · 2024Review
- Nature-Inspired Bioactive Compounds: A Promising Approach for Ferroptosis-Linked Human Diseases?Molecules (Basel, Switzerland) · 2023Review
- Redox Imbalance as a Common Pathogenic Factor Linking Hearing Loss and Cognitive Decline.Antioxidants (Basel, Switzerland) · 2023Review
- Does hearing loss lead to dementia? A review of the literature.Hearing research · 2021Review
- Glutamic Acid Transporters: Targets for Neuroprotective Therapies in Parkinson's Disease.Frontiers in neuroscience · 2021Review
- Antioxidant Effect of Propofol in Gliomas and Its Association With Divalent Metal Transporter 1.Frontiers in oncology · 2020Article
- Early Neurotoxic Effects of Inorganic Arsenic Modulate Cortical GSH Levels Associated With the Activation of the Nrf2 and NFκB Pathways, Expression of Amino Acid Transporters and NMDA Receptors and the Production of Hydrogen Sulfide.Frontiers in cellular neuroscience · 2020Article
- Induction of ferroptosis and mitochondrial dysfunction by oxidative stress in PC12 cells.Scientific reports · 2018Article
- Effects of Glycyrrhetinic Acid on GSH Synthesis Induced by Realgar in the Mouse Hippocampus: Involvement of System [Formula: see text], System [Formula: see text], MRP-1, and Nrf2.Molecular neurobiology · 2017Article
- Glutamine and glutaminolysis are required for efficient replication of infectious spleen and kidney necrosis virus in Chinese perch brain cells.Oncotarget · 2017Article
- Peritumoural glutamate correlates with post-operative seizures in supratentorial gliomas.Journal of neuro-oncology · 2016Article
- Resveratrol protects PC12 cells against OGD/ R-induced apoptosis via the mitochondrial-mediated signaling pathway.Acta biochimica et biophysica Sinica · 2016Article
- Kynurenines and Glutamate: Multiple Links and Therapeutic Implications.Advances in pharmacology (San Diego, Calif.) · 2016Review
- Characterization of a Novel Mutation in SLC1A1 Associated with Schizophrenia.Molecular neuropsychiatry · 2015Article
- SLC7A11 expression is associated with seizures and predicts poor survival in patients with malignant glioma.Science translational medicine · 2015Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Redox homeostasis is especially important in the brain where high oxygen consumption produces an abundance of harmful oxidative by-products. Glutathione (GSH) is a tripeptide non-protein thiol. It is the central nervous system's most abundant antioxidant and the master controller of brain redox homeostasis. The glutamate transporters, System xc(-) (SXC) and the Excitatory Amino Acid Transporters (EAAT), play important, synergistic roles in the synthesis of GSH. In glial cells, SXC mediates the uptake of cystine, which after intracellular reduction to cysteine, reacts with glutamate during the rate-limiting step of GSH synthesis. EAAT3 mediates direct cysteine uptake for neuronal GSH synthesis. SXC and EAAT work in concert in glial cells to provide two intracellular substrates for GSH synthesis, cystine and glutamate. Their cyclical basal function also prevents a buildup of extracellular glutamate, which SXC releases extracellularly in exchange for cystine uptake. Maintaining extracellular glutamate homeostasis is critical to prevent neuronal toxicity, as well as glutamate-mediated SXC inhibition, which could lead to a depletion of intracellular GSH and loss of cellular redox control. Many neurological diseases show evidence of GSH dysfunction, and increased GSH has been widely associated with chemotherapy and radiotherapy resistance of gliomas. We present evidence suggesting that gliomas expressing elevated levels of SXC are more reliant on GSH for growth and survival. They have an increased inherent radiation resistance, however, inhibition of SXC can increase tumor sensitivity at low radiation doses. GSH depletion through SXC inhibition may be a viable mechanism to enhance current glioma treatment strategies and make tumors more sensitive to radiation and chemotherapy protocols.
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