ArticleThe Journal of biological chemistry2015
Cystathionine is a novel substrate of cystine/glutamate transporter: implications for immune function.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 81 citations in OpenAlex.
- Integrated proteomic and metabolomic analyses implicate redox-metabolic pathways in PTSD-associated multisystem disease and accelerated aging.Nature communications · 2026Article
- Brain metabolomic profiling reveals ischemia-dominant disruption of metabolic pathways and tissue homeostasis in neonatal hypoxic-ischemic brain injury.Scientific reports · 2026Article
- Photodynamic activation of a KRAS RNA G-quadruplex-targeted photosensitizer induces ferroptosis in cisplatin-resistant non-small cell lung cancer.The Journal of biological chemistry · 2026Article
- 2D nanomaterial-triggered ferroptosis in cancer therapy.Journal of nanobiotechnology · 2025Review
- Novel neurotherapeutic targets for substance use disorders: Neuroplasticity, neuroinflammation, gasotransmitters and non-canonical organ systems.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Hydrogen sulfide/polysulfides signaling and neuronal diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Emerging regulated cell death mechanisms in bone remodeling: decoding ferroptosis, cuproptosis, disulfidptosis, and PANoptosis as therapeutic targets for skeletal disorders.Cell death discovery · 2025Review
- Evaluation of the Functional Properties and Edible Safety of Concocted Xanthii Fructus Protein.Foods (Basel, Switzerland) · 2025Article
- Traditional Chinese Medicine and Ferroptosis in Intracerebral Hemorrhage: A Potential Therapeutic Approach.Drug design, development and therapy · 2025Review
- Synergistic effect of regorafenib with aminoglycosides in ferroptosis-mediated liver injury.Frontiers in pharmacology · 2025Article
- Disulfidptosis, A Novel Cell Death Pathway: Molecular Landscape and Therapeutic Implications.Aging and disease · 2024Review
- Oxytosis/Ferroptosis in Neurodegeneration: the Underlying Role of Master Regulator Glutathione Peroxidase 4 (GPX4).Molecular neurobiology · 2024Review
- Antioxidant Systems as Modulators of Ferroptosis: Focus on Transcription Factors.Antioxidants (Basel, Switzerland) · 2024Review
- The application of approaches in detecting ferroptosis.Heliyon · 2024Review
- Broadening horizons: the multifaceted role of ferroptosis in breast cancer.Frontiers in immunology · 2024Review
- Review
- The mechanism of ferroptosis and its related diseases.Molecular biomedicine · 2023Review
- Ferroptosis-modulating small molecules for targeting drug-resistant cancer: Challenges and opportunities in manipulating redox signaling.Medicinal research reviews · 2023Review
- Critical Roles of the Cysteine-Glutathione Axis in the Production of γ-Glutamyl Peptides in the Nervous System.International journal of molecular sciences · 2023Review
- Neuroprotection of NRF2 against Ferroptosis after Traumatic Brain Injury in Mice.Antioxidants (Basel, Switzerland) · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cystine/glutamate transporter, designated as system xc(-), is important for maintaining intracellular glutathione levels and extracellular redox balance. The substrate-specific component of system xc(-), xCT, is strongly induced by various stimuli, including oxidative stress, whereas it is constitutively expressed only in specific brain regions and immune tissues, such as the thymus and spleen. Although cystine and glutamate are the well established substrates of system xc(-) and the knockout of xCT leads to alterations of extracellular redox balance, nothing is known about other potential substrates. We thus performed a comparative metabolite analysis of tissues from xCT-deficient and wild-type mice using capillary electrophoresis time-of-flight mass spectrometry. Although most of the analyzed metabolites did not show significant alterations between xCT-deficient and wild-type mice, cystathionine emerged as being absent specifically in the thymus and spleen of xCT-deficient mice. No expression of either cystathionine β-synthase or cystathionine γ-lyase was observed in the thymus and spleen of mice. In embryonic fibroblasts derived from wild-type embryos, cystine uptake was significantly inhibited by cystathionine in a concentration-dependent manner. Wild-type cells showed an intracellular accumulation of cystathionine when incubated in cystathionine-containing buffer, which concomitantly stimulated an increased release of glutamate into the extracellular space. By contrast, none of these effects could be observed in xCT-deficient cells. Remarkably, unlike knock-out cells, wild-type cells could be rescued from cystine deprivation-induced cell death by cystathionine supplementation. We thus conclude that cystathionine is a novel physiological substrate of system xc(-) and that the accumulation of cystathionine in immune tissues is exclusively mediated by system xc(-).
Indexed as
Identifiers
What OpenQuestion holds
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.