The Cystine/Glutamate Antiporter System xc− in Health and Disease: From Molecular Mechanisms to Novel Therapeutic Opportunities

Region- and Age-Specific Changes in Glutamate Transport in the AβPP23 Mouse Model for Alzheimer's Disease

(2018) Anneleen Schallier et al.   JOURNAL OF ALZHEIMERS DISEASE

Mechanisms of Oxidative Glutamate Toxicity: The Glutamate/Cystine Antiporter System xc¯ as a Neuroprotective Drug Target

(2012) Philipp Albrecht et al.   CNS & Neurological Disorders-Drug Targets

The Flavonoid Fisetin Attenuates Postischemic Immune Cell Infiltration, Activation and Infarct Size after Transient Cerebral Middle Artery Occlusion in Mice

(2012) Mathias Gelderblom et al.   JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM

Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation

(2011) R. V. Sekhar et al.   AMERICAN JOURNAL OF CLINICAL NUTRITION

Regulation of xCT expression and system $$ x_{\text{c}}^{ - } $$ function in neuronal cells

(2011) Jan Lewerenz et al.   AMINO ACIDS

Oxygen-Inducible Glutamate Oxaloacetate Transaminase as Protective Switch Transforming Neurotoxic Glutamate to Metabolic Fuel During Acute Ischemic Stroke

(2011) Cameron Rink et al.   ANTIOXIDANTS & REDOX SIGNALING

Posttranslational Modification of Cysteine in Redox Signaling and Oxidative Stress: Focus on S-Glutathionylation

(2011) John J. Mieyal et al.   ANTIOXIDANTS & REDOX SIGNALING

CD44 Variant Regulates Redox Status in Cancer Cells by Stabilizing the xCT Subunit of System xc− and Thereby Promotes Tumor Growth

(2011) Takatsugu Ishimoto et al.   CANCER CELL

Specific PET Imaging of xC−Transporter Activity Using a18F-Labeled Glutamate Derivative Reveals a Dominant Pathway in Tumor Metabolism

(2011) Norman Koglin et al.   CLINICAL CANCER RESEARCH

Sweet and Sour - Oxidative and Carbonyl Stress in Neurological Disorders

(2011) Robert A. Harris et al.   CNS & Neurological Disorders-Drug Targets

MicroRNA-26b is underexpressed in human breast cancer and induces cell apoptosis by targeting SLC7A11

(2011) Xiao-Xiao Liu et al.   FEBS LETTERS

Increased expression of cystine/glutamate antiporter in multiple sclerosis

(2011) Olatz Pampliega et al.   Journal of Neuroinflammation

Loss of System xFormula Does Not Induce Oxidative Stress But Decreases Extracellular Glutamate in Hippocampus and Influences Spatial Working Memory and Limbic Seizure Susceptibility

(2011) D. De Bundel et al.   JOURNAL OF NEUROSCIENCE

Glutamate release by primary brain tumors induces epileptic activity

(2011) Susan C Buckingham et al.   NATURE MEDICINE

Functional upregulation of system xc− by fibroblast growth factor-2

(2011) XiaoQian Liu et al.   NEUROPHARMACOLOGY

Fisetin Lowers Methylglyoxal Dependent Protein Glycation and Limits the Complications of Diabetes

(2011) Pamela Maher et al.   PLoS One

A Novel Neurotrophic Drug for Cognitive Enhancement and Alzheimer's Disease

(2011) Qi Chen et al.   PLoS One

Natural Vitamin E α-Tocotrienol Protects Against Ischemic Stroke by Induction of Multidrug Resistance-Associated Protein 1

(2011) Han-A Park et al.   STROKE

Necrostatin-1 ameliorates symptoms in R6/2 transgenic mouse model of Huntington's disease

(2011) S Zhu et al.   Cell Death & Disease

Methylglyoxal, glyoxalase 1 and the dicarbonyl proteome

(2010) Naila Rabbani et al.   AMINO ACIDS

Control of Redox State and Redox Signaling by Neural Antioxidant Systems

(2010) Jan Lewerenz et al.   ANTIOXIDANTS & REDOX SIGNALING

Polyphenols and health: Update and perspectives

(2010) Helmut Sies   ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS

Overexpression of xCT induces up-regulation of 14-3-3β in Kaposi's sarcoma

(2010) Yan Zeng et al.   BIOSCIENCE REPORTS

Extracellular hydrogen peroxide contributes to oxidative glutamate toxicity

(2010) Jong Seong Ha et al.   BRAIN RESEARCH

Erythropoietin-induced neuroprotection requires cystine glutamate exchanger activity

(2010) Brian Sims et al.   BRAIN RESEARCH

Synergistic protective effects of humanin and necrostatin-1 on hypoxia and ischemia/reperfusion injury

(2010) Xingshun Xu et al.   BRAIN RESEARCH

Critical role of the JNK-p53-GADD45α apoptotic cascade in mediating oxidative cytotoxicity in hippocampal neurons

(2010) Hye Joung Choi et al.   BRITISH JOURNAL OF PHARMACOLOGY

Glutamate, Excitatory Amino Acid Transporters, Xc−Antiporter, Glutamine Synthetase, and γ-Glutamyltranspeptidase in Human Corneal Epithelium

(2010) Marlyn P. Langford et al.   CURRENT EYE RESEARCH

Small molecule modulators of antioxidant response pathway

(2010) Wooyoung Hur et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Focus on Molecules: The cystine/glutamate exchanger (System xc−)

(2010) Julie C. Lim et al.   EXPERIMENTAL EYE RESEARCH

Depletion of GSH in glial cells induces neurotoxicity: relevance to aging and degenerative neurological diseases

(2010) Moonhee Lee et al.   FASEB JOURNAL

Dopaminergic neurons of system xc−-deficient mice are highly protected against 6-hydroxydopamine-induced toxicity

(2010) Ann Massie et al.   FASEB JOURNAL

A novel giant peroxisomal superoxide dismutase motif-containing protein

(2010) Diamandis Toutzaris et al.   FREE RADICAL BIOLOGY AND MEDICINE

Reactive oxygen species, cellular redox systems, and apoptosis

(2010) Magdalena L. Circu et al.   FREE RADICAL BIOLOGY AND MEDICINE

Cysteine/cystine redox signaling in cardiovascular disease

(2010) Young-Mi Go et al.   FREE RADICAL BIOLOGY AND MEDICINE

Regulation of System xc−Activity and Expression in Astrocytes by Interleukin-1β

(2010) Nicole A. Jackman et al.   GLIA

ERK activation by the polyphenols fisetin and resveratrol provides neuroprotection in multiple models of Huntington's disease

(2010) Pamela Maher et al.   HUMAN MOLECULAR GENETICS

System xc−and Thioredoxin Reductase 1 Cooperatively Rescue Glutathione Deficiency

(2010) Pankaj Kumar Mandal et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Delayed treatment with a novel neurotrophic compound reduces behavioral deficits in rabbit ischemic stroke

(2010) Paul A. Lapchak et al.   JOURNAL OF NEUROCHEMISTRY

Lactacidosis modulates glutathione metabolism and oxidative glutamate toxicity

(2010) Jan Lewerenz et al.   JOURNAL OF NEUROCHEMISTRY

Loss of Kelch-Like ECH-Associated Protein 1 Function in Prostate Cancer Cells Causes Chemoresistance and Radioresistance and Promotes Tumor Growth

(2010) P. Zhang et al.   MOLECULAR CANCER THERAPEUTICS

Molecular mechanisms of necroptosis: an ordered cellular explosion

(2010) Peter Vandenabeele et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

xCT deficiency accelerates chemically induced tumorigenesis

(2010) A. Nabeyama et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Reversing cocaine-induced synaptic potentiation provides enduring protection from relapse

(2010) K. Moussawi et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Transition to Addiction Is Associated with a Persistent Impairment in Synaptic Plasticity

(2010) F. Kasanetz et al.   SCIENCE

Current Views of Toll-Like Receptor Signaling Pathways

(2010) Masahiro Yamamoto et al.   Gastroenterology Research and Practice

Upregulation of xCT by KSHV-Encoded microRNAs Facilitates KSHV Dissemination and Persistence in an Environment of Oxidative Stress

(2010) Zhiqiang Qin et al.   PLoS Pathogens

Neuroprotective effects of zonisamide target astrocyte

(2009) Masato Asanuma et al.   ANNALS OF NEUROLOGY

Mitochondrial Glutathione, a Key Survival Antioxidant

(2009) Montserrat Marí et al.   ANTIOXIDANTS & REDOX SIGNALING

Hydrogen Sulfide Increases Glutathione Production and Suppresses Oxidative Stress in Mitochondria

(2009) Yuka Kimura et al.   ANTIOXIDANTS & REDOX SIGNALING

Aggravation of ischemia–reperfusion-triggered acute renal failure in xCT-deficient mice

(2009) Tomohiro Shibasaki et al.   ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS

Drosophilaexpresses a CD98 transporter with an evolutionarily conserved structure and amino acid-transport properties

(2009) Bruno Reynolds et al.   BIOCHEMICAL JOURNAL

Absence of iron-regulatory protein Hfe results in hyperproliferation of retinal pigment epithelium: role of cystine/glutamate exchanger

(2009) Jaya P. Gnana-Prakasam et al.   BIOCHEMICAL JOURNAL

Ceftriaxone Restores Glutamate Homeostasis and Prevents Relapse to Cocaine Seeking

(2009) Lori A. Knackstedt et al.   BIOLOGICAL PSYCHIATRY

Isoxazole analogues bind the System xc- transporter: Structure–activity relationship and pharmacophore model

(2009) Sarjubhai A. Patel et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Levetiracetam enhances endogenous antioxidant in the hippocampus of rats: In vivo evaluation by brain microdialysis combined with ESR spectroscopy

(2009) Yuto Ueda et al.   BRAIN RESEARCH

Effects of hyperglycemia and oxidative stress on the glutamate transporters GLAST and system xc − in mouse retinal Müller glial cells

(2009) Barbara Mysona et al.   CELL AND TISSUE RESEARCH

Necroptosis, necrosis and secondary necrosis converge on similar cellular disintegration features

(2009) T Vanden Berghe et al.   CELL DEATH AND DIFFERENTIATION

β-N-methylamino-l-alanine induces oxidative stress and glutamate release through action on system Xc−

(2009) XiaoQian Liu et al.   EXPERIMENTAL NEUROLOGY

Constitutive Reactive Oxygen Species Generation from Autophagosome/Lysosome in Neuronal Oxidative Toxicity

(2009) Chisato Kubota et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Induction of Nrf2 and xCT are involved in the action of the neuroprotective antibiotic ceftriaxonein vitro

(2009) Jan Lewerenz et al.   JOURNAL OF NEUROCHEMISTRY

12/15-Lipoxygenase targets neuronal mitochondria under oxidative stress

(2009) Stefanie Pallast et al.   JOURNAL OF NEUROCHEMISTRY

Pharmacogenomic Approach Reveals a Role for the xFormula Cystine/Glutamate Antiporter in Growth and Celastrol Resistance of Glioma Cell Lines

(2009) A.-N. Pham et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

N-Acetylcysteine reverses cocaine-induced metaplasticity

(2009) Khaled Moussawi et al.   NATURE NEUROSCIENCE

The glutamate homeostasis hypothesis of addiction

(2009) Peter W. Kalivas   NATURE REVIEWS NEUROSCIENCE

Extracellular thiol-assisted selenium uptake dependent on the xc- cystine transporter explains the cancer-specific cytotoxicity of selenite

(2009) E. Olm et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Targeting NRF2 signaling for cancer chemoprevention

(2009) Mi-Kyoung Kwak et al.   TOXICOLOGY AND APPLIED PHARMACOLOGY

ATF4-dependent transcription mediates signaling of amino acid limitation

(2009) Michael S. Kilberg et al.   TRENDS IN ENDOCRINOLOGY AND METABOLISM

Oxidative Stress, Lens Gap Junctions, and Cataracts

(2008) Viviana M. Berthoud et al.   ANTIOXIDANTS & REDOX SIGNALING

How do dietary flavanols improve vascular function? A position paper

(2008) Tankred Schewe et al.   ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS

Proteasome inhibitors prevent oxidative stress-induced nerve cell death by a novel mechanism

(2008) Pamela Maher   BIOCHEMICAL PHARMACOLOGY

The Role of Cystine-Glutamate Exchange in Nicotine Dependence in Rats and Humans

(2008) Lori A. Knackstedt et al.   BIOLOGICAL PSYCHIATRY

Molecular regulation of antioxidant ability in the hippocampus of EL mice

(2008) Mayuko Takaki et al.   BRAIN RESEARCH

The xc− cystine/glutamate antiporter: a mediator of pancreatic cancer growth with a role in drug resistance

(2008) M Lo et al.   BRITISH JOURNAL OF CANCER

Bid-induced release of AIF from mitochondria causes immediate neuronal cell death

(2008) S Landshamer et al.   CELL DEATH AND DIFFERENTIATION

Glutathione Peroxidase 4 Senses and Translates Oxidative Stress into 12/15-Lipoxygenase Dependent- and AIF-Mediated Cell Death

(2008) Alexander Seiler et al.   Cell Metabolism

The early phase of critical illness is a progressive acidic state due to unmeasured anions

(2008) B. Antonini et al.   EUROPEAN JOURNAL OF ANAESTHESIOLOGY

Characterization of the cystine/glutamate transporter in the outer plexiform layer of the vertebrate retina

(2008) Rebecca G. Hu et al.   EUROPEAN JOURNAL OF NEUROSCIENCE

Genetic variations and gene expression of transporters in drug disposition and response

(2008) Ying Huang et al.   Expert Opinion on Drug Metabolism & Toxicology

The solute carrier (SLC) complement of the human genome: Phylogenetic classification reveals four major families

(2008) Robert Fredriksson et al.   FEBS LETTERS

Nrf2-regulated glutathione recycling independent of biosynthesis is critical for cell survival during oxidative stress

(2008) C.J. Harvey et al.   FREE RADICAL BIOLOGY AND MEDICINE

Basal Levels of eIF2α Phosphorylation Determine Cellular Antioxidant Status by Regulating ATF4 and xCT Expression

(2008) Jan Lewerenz et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The Constitutively Active Orphan G-protein-coupled Receptor GPR39 Protects from Cell Death by Increasing Secretion of Pigment Epithelium-derived Growth Factor

(2008) Sonja Dittmer et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The xc− cystine/glutamate antiporter: A potential target for therapy of cancer and other diseases

(2008) Maisie Lo et al.   JOURNAL OF CELLULAR PHYSIOLOGY

Necrostatin-1 Reduces Histopathology and Improves Functional Outcome after Controlled Cortical Impact in Mice

(2008) Zerong You et al.   JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM

Interleukin-1β: a bridge between inflammation and excitotoxicity?

(2008) Birgit Fogal et al.   JOURNAL OF NEUROCHEMISTRY

A novel approach to enhancing cellular glutathione levels

(2008) Pamela Maher et al.   JOURNAL OF NEUROCHEMISTRY

A broadly neuroprotective derivative of curcumin

(2008) Yuanbin Liu et al.   JOURNAL OF NEUROCHEMISTRY

Neurodegeneration in multiple sclerosis: The role of oxidative stress and excitotoxicity

(2008) R.E. Gonsette   JOURNAL OF THE NEUROLOGICAL SCIENCES

Kaposi's Sarcoma-Associated Herpesvirus Forms a Multimolecular Complex of Integrins ( V 5,  V 3, and  3 1) and CD98-xCT during Infection of Human Dermal Microvascular Endothelial Cells, and CD98-xCT Is Essential for the Postentry Stage of Infection

(2008) M. V. Veettil et al.   JOURNAL OF VIROLOGY

Regulation of glutathione synthesis

(2008) Shelly C. Lu   MOLECULAR ASPECTS OF MEDICINE

Small interfering RNA–mediated xCT silencing in gliomas inhibits neurodegeneration and alleviates brain edema

(2008) Nicolai E Savaskan et al.   NATURE MEDICINE

The history of the pharmacology and cloning of ionotropic glutamate receptors and the development of idiosyncratic nomenclature

(2008) David Lodge   NEUROPHARMACOLOGY

Time-dependent changes in striatal xCT protein expression in hemi-Parkinson rats

(2008) Ann Massie et al.   NEUROREPORT

Blunted cystine–glutamate antiporter function in the nucleus accumbens promotes cocaine-induced drug seeking

(2008) K.S. Kau et al.   NEUROSCIENCE

Disruption of xCT inhibits cancer cell metastasis via the caveolin-1/β-catenin pathway

(2008) R-S Chen et al.   ONCOGENE

Opposing roles for caspase and calpain death proteases in l-glutamate-induced oxidative neurotoxicity

(2008) Lucy M. Elphick et al.   TOXICOLOGY AND APPLIED PHARMACOLOGY

N-Acetylcysteine Reduces Extinction Responding and Induces Enduring Reductions in Cue- and Heroin-Induced Drug-Seeking

(2007) Wenhua Zhou et al.   BIOLOGICAL PSYCHIATRY

A Prominent Role for Mucosal Cystine/Cysteine Metabolism in Intestinal Immunoregulation

(2007) Bernd Sido et al.   GASTROENTEROLOGY

Microdialysis of GABA and glutamate: Analysis, interpretation and comparison with microsensors

(2007) Miranda van der Zeyden et al.   PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR

Activation of microglia by secreted amyloid precursor protein evokes release of glutamate by cystine exchange and attenuates synaptic function

(2003) Steven W. Barger et al.   JOURNAL OF NEUROCHEMISTRY