cystine

Summary

Summary: A covalently linked dimeric nonessential amino acid formed by the oxidation of CYSTEINE. Two molecules of cysteine are joined together by a disulfide bridge to form cystine.

Top Publications

  1. ncbi The cystine knot motif in toxins and implications for drug design
    D J Craik
    Centre for Drug Design and Development, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia
    Toxicon 39:43-60. 2001
  2. pmc Role of cystine transport in intracellular glutathione level and cisplatin resistance in human ovarian cancer cell lines
    S Okuno
    Department of Obstetrics and Gynecology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan
    Br J Cancer 88:951-6. 2003
  3. pmc Stromal control of cystine metabolism promotes cancer cell survival in chronic lymphocytic leukaemia
    Wan Zhang
    Department of Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
    Nat Cell Biol 14:276-86. 2012
  4. pmc Myeloid-derived suppressor cells inhibit T-cell activation by depleting cystine and cysteine
    Minu K Srivastava
    Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, Maryland 21250, USA
    Cancer Res 70:68-77. 2010
  5. ncbi Thermal, chemical, and enzymatic stability of the cyclotide kalata B1: the importance of the cyclic cystine knot
    Michelle L Colgrave
    Institute for Molecular Bioscience, University of Queensland, Brisbane 4072, Australia
    Biochemistry 43:5965-75. 2004
  6. pmc Cysteine/cystine redox signaling in cardiovascular disease
    Young Mi Go
    Department of Medicine, Emory University, Atlanta, GA 30322, USA
    Free Radic Biol Med 50:495-509. 2011
  7. ncbi Engineered cystine knot peptides that bind alphavbeta3, alphavbeta5, and alpha5beta1 integrins with low-nanomolar affinity
    Richard H Kimura
    Department of Bioengineering, Cancer Center, Bio X Program, Stanford University, Stanford, California 94305, USA
    Proteins 77:359-69. 2009
  8. pmc Bursicon, the insect cuticle-hardening hormone, is a heterodimeric cystine knot protein that activates G protein-coupled receptor LGR2
    Ching Wei Luo
    Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305 5317, USA
    Proc Natl Acad Sci U S A 102:2820-5. 2005
  9. pmc Inhibition of cystine uptake disrupts the growth of primary brain tumors
    Wook Joon Chung
    Department of Neurobiology, Civitan International Research Center, The University of Alabama, Birmingham, Alabama 35294 0021, USA
    J Neurosci 25:7101-10. 2005
  10. ncbi Cystinosis
    William A Gahl
    Heritable Disorders Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892 1830, USA
    N Engl J Med 347:111-21. 2002

Detail Information

Publications280 found, 100 shown here

  1. ncbi The cystine knot motif in toxins and implications for drug design
    D J Craik
    Centre for Drug Design and Development, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia
    Toxicon 39:43-60. 2001
    The cystine knot structural motif is present in peptides and proteins from a variety of species, including fungi, plants, marine molluscs, insects and spiders...
  2. pmc Role of cystine transport in intracellular glutathione level and cisplatin resistance in human ovarian cancer cell lines
    S Okuno
    Department of Obstetrics and Gynecology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan
    Br J Cancer 88:951-6. 2003
    ..This system mediates cystine entry coupled with the exodus of intracellular glutamate and regulates the intracellular glutathione (GSH) levels ..
  3. pmc Stromal control of cystine metabolism promotes cancer cell survival in chronic lymphocytic leukaemia
    Wan Zhang
    Department of Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
    Nat Cell Biol 14:276-86. 2012
    ..Primary CLL cells from patients exhibit a limited ability to transport cystine for glutathione (GSH) synthesis owing to a low expression level of Xc-transporter...
  4. pmc Myeloid-derived suppressor cells inhibit T-cell activation by depleting cystine and cysteine
    Minu K Srivastava
    Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, Maryland 21250, USA
    Cancer Res 70:68-77. 2010
    ..Here we show that MDSCs also block T-cell activation by sequestering cystine and limiting the availability of cysteine...
  5. ncbi Thermal, chemical, and enzymatic stability of the cyclotide kalata B1: the importance of the cyclic cystine knot
    Michelle L Colgrave
    Institute for Molecular Bioscience, University of Queensland, Brisbane 4072, Australia
    Biochemistry 43:5965-75. 2004
    ..family of plant-derived peptides that have the unusual features of a head-to-tail cyclized backbone and a cystine knot core...
  6. pmc Cysteine/cystine redox signaling in cardiovascular disease
    Young Mi Go
    Department of Medicine, Emory University, Atlanta, GA 30322, USA
    Free Radic Biol Med 50:495-509. 2011
    ..The major thiol/disulfide redox couple in human plasma is cysteine (Cys) and its disulfide form, cystine (CySS)...
  7. ncbi Engineered cystine knot peptides that bind alphavbeta3, alphavbeta5, and alpha5beta1 integrins with low-nanomolar affinity
    Richard H Kimura
    Department of Bioengineering, Cancer Center, Bio X Program, Stanford University, Stanford, California 94305, USA
    Proteins 77:359-69. 2009
    ..Collectively, these data validate EETI-II as a scaffold for protein engineering, and highlight the development of unique integrin-binding peptides with potential for translational applications in cancer...
  8. pmc Bursicon, the insect cuticle-hardening hormone, is a heterodimeric cystine knot protein that activates G protein-coupled receptor LGR2
    Ching Wei Luo
    Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305 5317, USA
    Proc Natl Acad Sci U S A 102:2820-5. 2005
    ..Here we show that bursicon, to our knowledge the first heterodimeric cystine knot hormone found in insects, consists of two proteins encoded by the genes burs and pburs (partner of burs)...
  9. pmc Inhibition of cystine uptake disrupts the growth of primary brain tumors
    Wook Joon Chung
    Department of Neurobiology, Civitan International Research Center, The University of Alabama, Birmingham, Alabama 35294 0021, USA
    J Neurosci 25:7101-10. 2005
    ..We now show that glutamate release from glioma cells is an obligatory by-product of cellular cystine uptake via system xc-, an electroneutral cystine-glutamate exchanger...
  10. ncbi Cystinosis
    William A Gahl
    Heritable Disorders Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892 1830, USA
    N Engl J Med 347:111-21. 2002
  11. ncbi Cystine-glutamate transporter SLC7A11 in cancer chemosensitivity and chemoresistance
    Ying Huang
    Program of Pharmacogenomics, Department of Pharmacology, Comprehensive Cancer Center, Ohio State University, Columbus, Ohio 43210 1239, USA
    Cancer Res 65:7446-54. 2005
    ..xCT), together with SLC3A2 (4F2hc), encodes the heterodimeric amino acid transport system x(c)-, which mediates cystine-glutamate exchange and thereby regulates intracellular glutathione levels...
  12. ncbi The x(c)- cystine/glutamate antiporter: a potential target for therapy of cancer and other diseases
    Maisie Lo
    Department of Experimental Medicine, University of British Columbia, Vancouver, BC, Canada
    J Cell Physiol 215:593-602. 2008
    The x(c) (-) cystine/glutamate antiporter is a major plasma membrane transporter for the cellular uptake of cystine in exchange for intracellular glutamate...
  13. ncbi Dissection of mitogenic and neurodegenerative actions of cystine and glutamate in malignant gliomas
    N E Savaskan
    Institute of Cell Biology and Neurobiology, Charite Universitatsmedizin Berlin, Berlin, Germany
    Oncogene 30:43-53. 2011
    ..release glutamate through the amino-acid antiporter system X(c)(-), a process that is mechanistically linked with cystine incorporation...
  14. ncbi Sulfasalazine-induced cystine starvation: potential use for prostate cancer therapy
    Daniel W Doxsee
    Department of Cancer Endocrinology, BC Cancer Agency, Vancouver, British Columbia, Canada
    Prostate 67:162-71. 2007
    Certain cancers depend for growth on uptake of cystine/cysteine from their environment...
  15. ncbi The potential of cystine-knot microproteins as novel pharmacophoric scaffolds in oral peptide drug delivery
    Martin Werle
    ThioMatrix GmbH, Research Center Innsbruck, Mitterweg 24, 6020 Innsbruck, Austria
    J Drug Target 14:137-46. 2006
    Within this study, the potential of three clinically relevant microproteins (SE-AG-AZ, SE-EM and SE-EP) with cystine-knot architecture as pharmacophoric scaffolds for oral peptide delivery was investigated...
  16. ncbi Oxidative folding of peptides with cystine-knot architectures: kinetic studies and optimization of folding conditions
    Michael Reinwarth
    Institute for Organic Chemistry and Biochemistry, Technische Universitat Darmstadt, Petersenstr 22, 64287 Darmstadt, Germany
    Chembiochem 14:137-46. 2013
    ..Among them, cystine-knot peptides-commonly named "knottins"-make up a subclass with several thousand natural members...
  17. ncbi ERS1 encodes a functional homologue of the human lysosomal cystine transporter
    Xiao dong Gao
    Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan
    FEBS J 272:2497-511. 2005
    Cystinosis is a lysosomal storage disease caused by an accumulation of insoluble cystine in the lumen of the lysosome...
  18. ncbi Mechanisms of oxidative glutamate toxicity: the glutamate/cystine antiporter system xc- as a neuroprotective drug target
    Philipp Albrecht
    Department of Neurology, Heinrich Heine University Dusseldorf, Dusseldorf, Germany
    CNS Neurol Disord Drug Targets 9:373-82. 2010
    The glutamate/cystine antiporter system x(c)- transports cystine into cells in exchange for the important neurotransmitter glutamate at a ratio of 1:1...
  19. ncbi Corneal crystals in nephropathic cystinosis: natural history and treatment with cysteamine eyedrops
    W A Gahl
    Section on Human Biochemical Genetics, Heritable Disorders Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA
    Mol Genet Metab 71:100-20. 2000
    Although renal disease is the most prominent feature of the lysosomal storage disease cystinosis, corneal cystine crystal formation remains a major complication, leading to photophobia, corneal erosions, and keratopathies...
  20. pmc An unusual structural motif of antimicrobial peptides containing end-to-end macrocycle and cystine-knot disulfides
    J P Tam
    Department of Microbiology and Immunology, Vanderbilt University, A 5119 MCN, 1161 21st Avenue South, Nashville, TN 37232 2363, USA
    Proc Natl Acad Sci U S A 96:8913-8. 1999
    Four macrocyclic cystine-knot peptides of 29-31 residues, kalata, circulin A and B (CirA and CirB), and cyclopsychotride, have been isolated from coffee plants but have undetermined physiological functions...
  21. ncbi Neuroadaptations in cystine-glutamate exchange underlie cocaine relapse
    David A Baker
    Department of Physiology and Neuroscience, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    Nat Neurosci 6:743-9. 2003
    ..in vivo extracellular glutamate in the nucleus accumbens of rats by decreasing the exchange of extracellular cystine for intracellular glutamate...
  22. ncbi Compromised glutamate transport in human glioma cells: reduction-mislocalization of sodium-dependent glutamate transporters and enhanced activity of cystine-glutamate exchange
    Z C Ye
    Department of Neurobiology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
    J Neurosci 19:10767-77. 1999
    ..In glioma cell lines, over 50% of glutamate transport was Na(+)-independent and mediated by a cystine-glutamate exchanger (system x(c)(-))...
  23. ncbi Redox imbalance in cystine/glutamate transporter-deficient mice
    Hideyo Sato
    Department of Biochemistry, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan
    J Biol Chem 280:37423-9. 2005
    b>Cystine/glutamate transporter, designated as system x(-)(c), mediates cystine entry in exchange for intracellular glutamate in mammalian cells...
  24. ncbi The oxidative stress-inducible cystine/glutamate antiporter, system x (c) (-) : cystine supplier and beyond
    Marcus Conrad
    DZNE, German Center for Neurodegenerative Diseases, Munich, 80336, Munich, Germany
    Amino Acids 42:231-46. 2012
    The oxidative stress-inducible cystine/glutamate exchange system, system x (c) (-) , transports one molecule of cystine, the oxidized form of ..
  25. ncbi Plant cyclotides: A unique family of cyclic and knotted proteins that defines the cyclic cystine knot structural motif
    D J Craik
    Centre for Drug Design and Development, The University of Queensland, Brisbane, QLD 4072, Australia
    J Mol Biol 294:1327-36. 1999
    ..The structure consists of a distorted triple-stranded beta-sheet and a cystine-knot arrangement of the disulfide bonds...
  26. pmc Extracellular thiol-assisted selenium uptake dependent on the x(c)- cystine transporter explains the cancer-specific cytotoxicity of selenite
    Eric Olm
    Division of Pathology F46, Department of Laboratory Medicine, Karolinska Institutet, Stockholm SE 141 86, Sweden
    Proc Natl Acad Sci U S A 106:11400-5. 2009
    ..The extracellular reduction is mediated by cysteine, and the efficacy is determined by the uptake of cystine by the x(c)(-) antiporter and secretion of cysteine by multidrug resistance proteins, both of which are ..
  27. ncbi Molecular pathogenesis of cystinosis: effect of CTNS mutations on the transport activity and subcellular localization of cystinosin
    Vasiliki Kalatzis
    Inserm U574, Hopital Necker Enfants Malades, Paris, France
    Hum Mol Genet 13:1361-71. 2004
    Cystinosis is an inherited disorder characterized by defective lysosomal efflux of cystine. Three clinical forms (infantile, juvenile and ocular cystinosis) have been described according to the age of onset and severity of the symptoms...
  28. ncbi Transcriptional control of cystine/glutamate transporter gene by amino acid deprivation
    Hideyo Sato
    Department of Biochemistry, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305 8575, Japan
    Biochem Biophys Res Commun 325:109-16. 2004
    ..System x(c)(-) is an anionic amino acid transport system highly specific for cystine and glutamate, and its activity is known to be induced by cystine deprivation...
  29. pmc Oxidation of plasma cysteine/cystine redox state in endotoxin-induced lung injury
    Smita S Iyer
    Department of Medicine, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA
    Am J Respir Cell Mol Biol 40:90-8. 2009
    ..Cysteine (Cys) and its disulfide Cystine (CySS) constitute the most abundant, low-molecular-weight thiol/disulfide redox couple in the plasma, and Cys ..
  30. ncbi Simple classification of renal calculi closely related to their micromorphology and etiology
    Felix Grases
    Laboratory of Renal Lithiasis Research, Faculty of Sciences, University of Balearic Islands, Ctra Valldemossa km 7 5, 07071 Palma de Mallorca, Spain
    Clin Chim Acta 322:29-36. 2002
    ..Classification of renal calculi with clear correlation with the main urinary etiological conditions has been previously established. However, such information is complex and difficult to adapt to clinical routine practice...
  31. ncbi Evaluation and improvement of the properties of the novel cystine-knot microprotein McoEeTI for oral administration
    M Werle
    ThioMatrix GmbH, Research Center Innsbruck, Mitterweg 24, 6020 Innsbruck, Austria
    Int J Pharm 332:72-9. 2007
    b>Cystine-knot microproteins exhibit several properties that make them highly interesting as scaffolds for oral peptide drug delivery...
  32. pmc Features of a spatially constrained cystine loop in the p10 FAST protein ectodomain define a new class of viral fusion peptides
    Christopher Barry
    Department of Microbiology and Immunology, Nova Scotia B3H 1X5, Canada
    J Biol Chem 285:16424-33. 2010
    ..conserved cysteine residues flanking the p10 HP form an essential intramolecular disulfide bond to create a cystine loop...
  33. pmc A key role for mitochondria in endothelial signaling by plasma cysteine/cystine redox potential
    Young Mi Go
    Division of Pulmonary Medicine, Emory University, Atlanta, GA 30322, USA
    Free Radic Biol Med 48:275-83. 2010
    The redox potential of the plasma cysteine/cystine couple (E(h)CySS) is oxidized in association with risk factors for cardiovascular disease (CVD), including age, smoking, type 2 diabetes, obesity, and alcohol abuse...
  34. ncbi Structure of a novel P-superfamily spasmodic conotoxin reveals an inhibitory cystine knot motif
    Luke A Miles
    The Walter and Eliza Hall Institute of Medical Research, NMR Laboratory, 381 Royal Parade, Parkville 3052, Australia
    J Biol Chem 277:43033-40. 2002
    ..structure of gm9a in aqueous solution and demonstrated that the molecule adopts the well known inhibitory cystine knot motif constrained by three disulfide bonds involving Cys(2)-Cys(16), Cys(6)-Cys(18) and Cys(12)-Cys(23)...
  35. ncbi Molecular architecture and biorecognition processes of the cystine knot protein superfamily: part I. The glycoprotein hormones
    M T Hearn
    Centre for Bioprocess Technology, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3168, Australia
    J Mol Recognit 13:223-78. 2000
    In this review article, the reader is introduced to recent advances in our knowledge on a subset of the cystine knot superfamily of homo- and hetero-dimeric proteins, from the perspective of the endocrine glycoprotein hormone family of ..
  36. pmc Postprandial cysteine/cystine redox potential in human plasma varies with meal content of sulfur amino acids
    Youngja Park
    Division of Pulmonary, Allergy and Critical Care Medicine, Emory University, Atlanta, GA 30322, USA
    J Nutr 140:760-5. 2010
    ..study, we had 2 aims: to determine whether the SAA content of a meal affected postprandial plasma cysteine (Cys), cystine (CySS), or redox potential (E(h)CySS) in humans and whether SAA intake level (adequate or inadequate) in the days ..
  37. pmc Cystine 186-cystine 209 disulfide bond is not essential for the procoagulant activity of tissue factor or for its de-encryption
    Hema Kothari
    Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA
    Blood 115:4273-83. 2010
    ..Here, we critically evaluated the importance of cystine 186-cystine 209 (Cys186-Cys209) bond formation for TF procoagulant activity and its de-encryption...
  38. pmc The cystine/glutamate antiporter system x(c)(-) in health and disease: from molecular mechanisms to novel therapeutic opportunities
    Jan Lewerenz
    Department of Neurology, University of Ulm, Ulm, Germany
    Antioxid Redox Signal 18:522-55. 2013
    The antiporter system x(c)(-) imports the amino acid cystine, the oxidized form of cysteine, into cells with a 1:1 counter-transport of glutamate...
  39. pmc Stem cell microvesicles transfer cystinosin to human cystinotic cells and reduce cystine accumulation in vitro
    Diana M Iglesias
    Department of Pediatrics, Montreal Children s Hospital Research Institute, McGill University, Montreal, Quebec, Canada
    PLoS ONE 7:e42840. 2012
    Cystinosis is a rare disease caused by homozygous mutations of the CTNS gene, encoding a cystine efflux channel in the lysosomal membrane...
  40. pmc Increased expression of cystine/glutamate antiporter in multiple sclerosis
    Olatz Pampliega
    Neurotek UPV EHU, Parque Tecnologico de Bizkaia, Zamudio, Bizkaia, Spain
    J Neuroinflammation 8:63. 2011
    ..In addition to glutamate transporters, levels of extracellular glutamate are controlled by cystine/glutamate antiporter x(c)⁻, an exchanger that provides intracellular cystine for production of glutathione, the ..
  41. ncbi Molecular jamming--the cystine slipknot mechanical clamp in all-atom simulations
    Lukasz Pepłowski
    Institute of Physics, Nicolaus Copernicus University, Torun, Poland
    J Chem Phys 134:085102. 2011
    ..Such high force peaks should be due to forcing of a slip-loop through a cystine ring, i.e., by generating a cystine slipknot. The survey has been performed in a simple coarse grained model...
  42. ncbi Complete amino acid sequence of puroindoline, a new basic and cystine-rich protein with a unique tryptophan-rich domain, isolated from wheat endosperm by Triton X-114 phase partitioning
    J E Blochet
    Laboratoire de Biochimie et Technologie des Proteines, INRA, Nantes, France
    FEBS Lett 329:336-40. 1993
    ..The similar phase partitioning behavior in Triton X-114 of this basic cystine-rich protein and of purothionins suggests that puroindoline may also be a membranotoxin that might play a role in ..
  43. pmc Plasma L-cystine/L-glutamate imbalance increases tumor necrosis factor-alpha from CD14+ circulating monocytes in patients with advanced cirrhosis
    Eiji Kakazu
    Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aobaku, Sendai, Japan
    PLoS ONE 6:e23402. 2011
    ..Previous studies reported that antigen-presenting cells take up L-Cystine (L-Cys) and secrete substantial amounts of L-Glutamate (L-Glu) via the transport system Xc- (4F2hc+xCT), and that ..
  44. pmc Thinking outside the cleft to understand synaptic activity: contribution of the cystine-glutamate antiporter (System xc-) to normal and pathological glutamatergic signaling
    Richard Bridges
    Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, Montana, USA
    Pharmacol Rev 64:780-802. 2012
    ..Also called a cystine-glutamate antiporter, system x(c)(-) typically functions by exchanging one molecule of extracellular cystine for ..
  45. ncbi Ultra-stable peptide scaffolds for protein engineering-synthesis and folding of the circular cystine knotted cyclotide cycloviolacin O2
    Teshome Leta Aboye
    Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre, Box 574, SE 751 23 Uppsala, Sweden
    Chembiochem 9:103-13. 2008
    The cyclic cystine knot motif, as defined by the cyclotide peptide family, is an attractive scaffold for protein engineering...
  46. ncbi Suppression by glutamate of proliferative activity through glutathione depletion mediated by the cystine/glutamate antiporter in mesenchymal C3H10T1/2 stem cells
    Mika Iemata
    Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Natural Science and Technology, Kanazawa, Ishikawa, Japan
    J Cell Physiol 213:721-9. 2007
    ..Expression of mRNA was for the first time shown with the cystine/Glu antiporter composed of xCT and 4F2hc subunits, in addition to particular excitatory amino acid transporter (..
  47. pmc Dietary sulfur amino acid effects on fasting plasma cysteine/cystine redox potential in humans
    Dean P Jones
    Division of Pulmonary, Allergy and Critical Care Medicine, Emory University, Atlanta, Georgia, USA
    Nutrition 27:199-205. 2011
    Oxidation of plasma cysteine/cystine (Cys/CySS) redox potential (E(h)CySS) has been associated with risk factors for cardiovascular disease in humans...
  48. pmc Dietary cystine level affects metabolic rate and glycaemic control in adult mice
    Amany K Elshorbagy
    Department of Pharmacology, University of Oxford, UK
    J Nutr Biochem 23:332-40. 2012
    ..investigated the body composition, metabolic rate and metabolic phenotype of mature C3H/HeH mice assigned to low-cystine (LC) or high-cystine (HC) diets for 12 weeks. Compared to LC mice, HC mice gained more weight (P=...
  49. pmc Measuring the poise of thiol/disulfide couples in vivo
    Dean P Jones
    Clinical Biomarkers Laboratory, Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
    Free Radic Biol Med 47:1329-38. 2009
    The reduction potentials (E(h)) for the redox couples GSH/GSSG and cysteine/cystine (Cys/CySS) in plasma are useful indicators of systemic oxidative stress and other medically relevant physiological states...
  50. pmc Glutamate suppresses osteoclastogenesis through the cystine/glutamate antiporter
    Eiichi Hinoi
    Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Natural Science and Technology, Kakuma machi, Kanazawa, Ishikawa 920 1192, Japan
    Am J Pathol 170:1277-90. 2007
    ..expression of mRNA was seen with glutamate transporters, such as excitatory amino acid transporters and cystine/glutamate antiporter, in primary osteoclasts...
  51. ncbi Snapshots of the cystine lyase C-DES during catalysis. Studies in solution and in the crystalline state
    Jens T Kaiser
    Max Planck Institut fur Biochemie, Abt Strukturforschung, Am Klopferspitz 18a, Martinsried 82152, Germany
    J Biol Chem 278:357-65. 2003
    The cystine lyase (C-DES) of Synechocystis is a pyridoxal-5'-phosphate-dependent enzyme distantly related to the family of NifS-like proteins. The crystal structure of an N-terminal modified variant has recently been determined...
  52. ncbi A negative correlation between expression profiles of runt-related transcription factor-2 and cystine/glutamate antiporter xCT subunit in ovariectomized mouse bone
    Kyosuke Uno
    Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Natural Science and Technology, Ishikawa, Japan
    J Pharmacol Sci 115:309-19. 2011
    ..associated with the depletion of intracellular GSH after promoting the retrograde operation of the bidirectional cystine/Glu antiporter in undifferentiated osteoblastic MC3T3-E1 cells...
  53. ncbi The cystine knot structure of ion channel toxins and related polypeptides
    R S Norton
    Biomolecular Research Institute, Parkville, Australia
    Toxicon 36:1573-83. 1998
    ..toxins and related polypeptides have been found to adopt a common structural motif designated the inhibitor cystine knot motif (Pallaghy P. K., Nielsen, K. J., Craik, D. J., Norton, R. S...
  54. pmc Intralysosomal cystine accumulation in mice lacking cystinosin, the protein defective in cystinosis
    Stephanie Cherqui
    INSERM U423, Hopital Necker Enfants Malades, Paris, France
    Mol Cell Biol 22:7622-32. 2002
    Cystinosis is an autosomal recessive disorder characterized by an accumulation of intralysosomal cystine. The causative gene, CTNS, encodes cystinosin, a seven-transmembrane-domain protein, which we recently showed to be a lysosomal ..
  55. ncbi Measurement of cystine in granulocytes using liquid chromatography-tandem mass spectrometry
    A Chabli
    AP HP, Hopital Necker Enfants Malades, Service de Biochimie B, Universite Paris V, 75015 Paris, France
    Clin Biochem 40:692-8. 2007
    Cystinosis is a rare autosomal recessive disorder characterized by an accumulation of intralysosomal cystine due to a defect in cystine transport across the lysosomal membrane...
  56. ncbi Identification and characterization of uptake systems for cystine and cysteine in cultured astrocytes and neurons: evidence for methylmercury-targeted disruption of astrocyte transport
    G Shanker
    Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1083, USA
    J Neurosci Res 66:998-1002. 2001
    ..The review summarizes recent observations on transport systems for cysteine and cystine, precursors of GSH, in primary cultures of astrocytes and neurons, and their sensitivity to MeHg treatment.
  57. pmc Late-onset nephropathic cystinosis: clinical presentation, outcome, and genotyping
    Aude Servais
    Department of Nephrology, Necker Hospital, 149 rue de Sevres, 75015 Paris, France
    Clin J Am Soc Nephrol 3:27-35. 2008
    Cystinosis is an autosomal recessive disease characterized by the intralysosomal accumulation of cystine, as a result of a defect in cystine transport across the lysosomal membrane...
  58. ncbi Evaluation of treatment with cysteamine eyedrops for cystinosis with confocal microscopy
    Rui Tavares
    Ophthalmology Department, Coimbra University Hospital, Coimbra, Portugal
    Cornea 28:938-40. 2009
    ..1136% (new formulation, now stable at room temperature without the need for refrigeration for up to 2 months) for the treatment of cystine crystals in the cornea using slit lamp biomicroscopy and confocal microscopy.
  59. ncbi The cystine/cysteine cycle: a redox cycle regulating susceptibility versus resistance to cell death
    A Banjac
    GSF Forschungszentrum für Umwelt und Gesundheit, Institut für Klinische Molekularbiologie und Tumorgenetik, Munchen, Germany
    Oncogene 27:1618-28. 2008
    ..Cysteine, typically present in its oxidized form cystine in the extracellular space, is regarded as the rate-limiting substrate for glutathione (GSH) synthesis...
  60. ncbi Evolution and classification of cystine knot-containing hormones and related extracellular signaling molecules
    U A Vitt
    Division of Reproductive Biology Department of Gynecology and Obstetrics Stanford University School of Medicine Stanford, California 94305 5317, USA
    Mol Endocrinol 15:681-94. 2001
    The cystine knot three-dimensional structure is found in many extracellular molecules and is conserved among divergent species...
  61. pmc Cysteine metabolism in Legionella pneumophila: characterization of an L-cystine-utilizing mutant
    Fanny Ewann
    Division of Infectious Diseases, University of Virginia Health Systems, MR 4 Building, Room 2146, 409 Lane Road, Charlottesville, VA 22908, USA
    Appl Environ Microbiol 72:3993-4000. 2006
    ..of Legionella pneumophila on buffered charcoal-yeast extract (BCYE) medium is dependent on L-cysteine (but not L-cystine), which is added in excess over what is required for nutrition...
  62. ncbi The importance of having high glutathione (GSH) level after bovine in vitro maturation on embryo development effect of beta-mercaptoethanol, cysteine and cystine
    D G De Matos
    HALITUS, Instituto Médico, Buenos Aires, Argentina
    Theriogenology 53:761-71. 2000
    Supplementation of IVM medium with cysteamine, beta-mercaptoethanol, cysteine and cystine induced bovine oocyte glutathione (GSH) synthesis, but only the effect of cysteamine on the developmental competence of these oocytes was tested...
  63. ncbi Glutathione synthesis during in vitro maturation of bovine oocytes: role of cumulus cells
    D G De Matos
    Centro de Investigaciones Reproductivas Perez Companc, Buenos Aires, Argentina
    Biol Reprod 57:1420-5. 1997
    ..out to evaluate the role of cumulus cells in GSH synthesis during IVM of bovine oocytes in the presence of cystine, cysteine, the cysteine analogue N-acetylcysteine, and cysteamine...
  64. pmc Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein
    M E Brunkow
    Celltech Inc, Bothell, WA 98021, USA
    Am J Hum Genet 68:577-89. 2001
    ..The SOST gene encodes a protein that shares similarity with a class of cystine knot-containing factors including dan, cerberus, gremlin, prdc, and caronte...
  65. ncbi Cystine/glutamate exchange modulates glutathione supply for neuroprotection from oxidative stress and cell proliferation
    Andy Y Shih
    Kinsmen Laboratory of Neurological Research and Brain Research Center, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3
    J Neurosci 26:10514-23. 2006
    The cystine/glutamate exchanger (xCT) provides intracellular cyst(e)ine for production of glutathione, a major cellular antioxidant...
  66. pmc The cystine/glutamate antiporter regulates dendritic cell differentiation and antigen presentation
    June A D'Angelo
    Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Science Center, New Orleans, LA 70112, USA
    J Immunol 185:3217-26. 2010
    ..Glutathione synthesis depends on the cystine/glutamate antiporter, which transports the rate-limiting precursor cystine into the cell in exchange for ..
  67. ncbi Promoting effect of beta-mercaptoethanol on in vitro development under oxidative stress and cystine uptake of bovine embryos
    M Takahashi
    Department of Animal and Grassland Research, National Agricultural Center for Kyushu Okinawa Region, Kumamoto 861 1192, Japan
    Biol Reprod 66:562-7. 2002
    The effects of beta-mercaptoethanol (beta-ME) on in vitro development under oxidative stress and cystine uptake of bovine embryos were investigated...
  68. ncbi Design, pharmacology, and NMR structure of a minimized cystine knot with agouti-related protein activity
    Pilgrim J Jackson
    Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, USA
    Biochemistry 41:7565-72. 2002
    ..and suggested that melanocortin receptor contacts were made primarily by two loops presented by a well-structured cystine knot domain within AGRP(87-132) [McNulty et al. (2001) Biochemistry 40, 15520-15527]...
  69. ncbi Evolutionary origin of inhibitor cystine knot peptides
    Shunyi Zhu
    Laboratory of Toxicology, University of Leuven, Belgium
    FASEB J 17:1765-7. 2003
    The inhibitor cystine knot (ICK) fold is an evolutionarily conserved structural motif shared by a large group of polypeptides with diverse sequences and bioactivities...
  70. ncbi Effect of oxygen on induction of the cystine transporter by bacterial lipopolysaccharide in mouse peritoneal macrophages
    H Sato
    Department of Biochemistry, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305 8575 Japan
    J Biol Chem 276:10407-12. 2001
    ..We reported previously that transport activities of cystine and arginine in the macrophages were induced markedly by low concentrations of bacterial lipopolysaccharide (LPS)...
  71. ncbi Prediction of the bonding states of cysteines using the support vector machines based on multiple feature vectors and cysteine state sequences
    Yu Ching Chen
    Institute of Bioinformatics, National Chiao Tung University, Hsinchu, Taiwan, ROC
    Proteins 55:1036-42. 2004
    ..77 Matthews correlation coefficient, around 10% and 22% higher than the corresponding values obtained by SVM based on local sequence information...
  72. ncbi Glutamate preferentially suppresses osteoblastogenesis than adipogenesis through the cystine/glutamate antiporter in mesenchymal stem cells
    Mika Takarada-Iemata
    Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Natural Science and Technology, Kanazawa, Ishikawa, Japan
    J Cell Physiol 226:652-65. 2011
    ..In cells with Runx2 adenovirus, the cystine/Glu antiporter substrate cystine significantly prevented the decreases by Glu in both ALP staining and ..
  73. ncbi Pharmacogenomic approach reveals a role for the x(c)- cystine/glutamate antiporter in growth and celastrol resistance of glioma cell lines
    Anh Nhan Pham
    Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA
    J Pharmacol Exp Ther 332:949-58. 2010
    The x(c)(-) cystine/glutamate antiporter has been implicated in GSH-based chemoresistance because it mediates cellular uptake of cystine/cysteine for sustenance of intracellular GSH levels...
  74. ncbi Differentiation of substrate and non-substrate inhibitors of transport system xc(-): an obligate exchanger of L-glutamate and L-cystine
    Sarjubhai A Patel
    Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT 59812, USA
    Neuropharmacology 46:273-84. 2004
    ..exchanger that normally couples the export of intracellular L-glutamate with the import of extracellular L-cystine. Two cell lines that express high levels of system x(c)(-) are used to delineate the pharmacology of the ..
  75. ncbi Expression and developmental regulation of the cystine/glutamate exchanger (xc-) in the rat
    Vincenzo La Bella
    Department of Clinical Neurosciences, Laboratory of Neurochemistry, University of Palermo, Palermo, Italy
    Neurochem Res 32:1081-90. 2007
    The cystine/glutamate exchanger (antiporter x (c) (-) ) is a membrane transporter involved in the uptake of cystine, the rate-limiting amino acid in the synthesis of glutathione...
  76. ncbi Cystine transport is defective in isolated leukocyte lysosomes from patients with cystinosis
    W A Gahl
    Science 217:1263-5. 1982
    The activity of a cystine transport system in lysosomes prepared from the leukocytes of patients with cystinosis was found to be deficient...
  77. pmc Overproduction of L-cysteine and L-cystine by Escherichia coli strains with a genetically altered serine acetyltransferase
    S Nakamori
    Department of Bioscience, Fukui Prefectural University, Japan
    Appl Environ Microbiol 64:1607-11. 1998
    Organisms that overproduced L-cysteine and L-cystine from glucose were constructed by using Escherichia coli K-12 strains...
  78. ncbi Cystine/glutamate exchange serves as the source for extracellular glutamate: modifications by repeated cocaine administration
    D A Baker
    Department of Physiology and Neuroscience, Medical University of South Carolina, Charleston South Carolina 29425, USA
    Amino Acids 23:161-2. 2002
    ..The studies presented reveal that this long-term neuroadaptation elicited by repeated cocaine results from a decrease in the activity of cystine/glutamate exchange.
  79. ncbi Structural basis of BMP signalling inhibition by the cystine knot protein Noggin
    Jay Groppe
    Structural Biology, Salk Institute, 10010 North Torrey Pines Road, La Jolla, California 92037, USA
    Nature 420:636-42. 2002
    ..The scaffold of Noggin contains a cystine (the oxidized form of cysteine) knot topology similar to that of BMPs; thus, ligand and antagonist seem to have ..
  80. ncbi A bacterial expression system revisited for the recombinant production of cystine-rich plant lipid transfer proteins
    Khalil Elmorjani
    Unité de Recherche sur les Protéines Végétales et leurs Interactions, INRA, Rue de la Géraudière 44316 Nantes Cedex 3, France
    Biochem Biophys Res Commun 316:1202-9. 2004
    Non-specific lipid transfer proteins (nsLTPs) are abundant and ubiquitous cystine-rich proteins that are capable, in vitro, of binding lipids and hydrophobic molecules...
  81. ncbi Formation of insulin fragments by insulin-degrading enzyme: the role of zinc(II) and cystine bridges
    Francesco Bellia
    Istituto Biostrutture e Bioimmagini, CNR, Viale A Doria 6, Catania, Italy
    J Mass Spectrom 48:135-40. 2013
    ..In this work, the role of zinc(II) and cystine bridges in the degradation of insulin by IDE are investigated by high-performance liquid chromatography-mass ..
  82. ncbi Correlations of cationic charges with salt sensitivity and microbial specificity of cystine-stabilized beta -strand antimicrobial peptides
    James P Tam
    Department of Microbiology and Immunology, Vanderbilt University, A5119 MCN, Nashville, Tennessee 37232 2363, USA
    J Biol Chem 277:50450-6. 2002
    ..between charge clusters and salt insensitivity and microbial specificity in linear, cyclic, and retro-isomeric cystine-stabilized beta-strand (CSbeta) tachyplesin (TP) in a panel of 10 test organisms...
  83. ncbi Localization of disulfide bonds in the cystine knot domain of human von Willebrand factor
    A Katsumi
    Howard Hughes Medical Institute, Department of Medicine and Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO 63110, USA
    J Biol Chem 275:25585-94. 2000
    ..into the endoplasmic reticulum, proVWF subunits dimerize through disulfide bonds between their C-terminal cystine knot-like (CK) domains. CK domains are characterized by six conserved cysteines...
  84. pmc The xc- cystine/glutamate antiporter: a mediator of pancreatic cancer growth with a role in drug resistance
    M Lo
    Department of Experimental Medicine, University of British Columbia, Vancouver, BC, Canada
    Br J Cancer 99:464-72. 2008
    The x(c)(-) cystine transporter enhances biosynthesis of glutathione, a tripeptide thiol important in drug resistance and cellular defense against oxidative stress, by enabling cellular uptake of cystine, a rate-limiting precursor...
  85. pmc Unique scorpion toxin with a putative ancestral fold provides insight into evolution of the inhibitor cystine knot motif
    Jennifer J Smith
    Institute for Molecular Bioscience and School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia QLD 4072, Australia
    Proc Natl Acad Sci U S A 108:10478-83. 2011
    The three-disulfide inhibitor cystine knot (ICK) motif is a fold common to venom peptides from spiders, scorpions, and aquatic cone snails...
  86. pmc Tying the knot: the cystine signature and molecular-recognition processes of the vascular endothelial growth factor family of angiogenic cytokines
    Shalini Iyer
    Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, UK
    FEBS J 278:4304-22. 2011
    The cystine-knot motif, made up of three intertwined disulfide bridges, is a unique feature of several toxins, cyclotides and growth factors, and occurs in a variety of species, including fungi, insects, molluscs and mammals...
  87. pmc Tiny cystine stones in the gallbladder of a patient with cholecystolithiasis complicating acute cholecystitis: a case report
    Tie Qiao
    Institute of Gallbladder Disease of Panyu, Guangzhou 511470, People s Republic of China
    Eur J Med Res 17:6. 2012
    b>Cystine stones, the main component of which is cystine, are very common urinary calculi, but are rare in the gall bladder...
  88. pmc High cystine in platelets from patients with nephropathic cystinosis: a chemical, ultrastructural, and functional evaluation
    L Olcay
    Section of Paediatric Haematology, Ankara Oncology Hospital, Demetevler, 06200 Ankara, Turkey
    J Clin Pathol 58:939-45. 2005
    ..To investigate the morphology and function of platelets in nephropathic cystinosis (NC)...
  89. ncbi Suppression of cystine uptake by sulfasalazine inhibits proliferation of human mammary carcinoma cells
    Vishal S Narang
    College of Pharmacy, University of Cincinnati, 3223 Eden Ave, Cincinnati, OH 45267 0004, USA
    Anticancer Res 23:4571-9. 2003
    Malignant progression of lymphoma cells is associated with acquisition of the cystine/glutamate antiporter, xc-, enhancing cystine uptake. Recently, we showed that sulfasalazine (SASP) is a specific xc- inhibitor...
  90. ncbi Comparison of collision-induced dissociation and electron-induced dissociation of singly protonated aromatic amino acids, cystine and related simple peptides using a hybrid linear ion trap-FT-ICR mass spectrometer
    Hadi Lioe
    School of Chemistry, University of Melbourne, Melbourne, Victoria 3010, Australia
    Anal Bioanal Chem 389:1429-37. 2007
    ..EID may find applications in analyzing singly charged molecular ions formed by matrix-assisted laser desorption ionization...
  91. ncbi Cystine starvation induces reversible large-body formation from nuclear bodies in T24 cells
    H Kamei
    Laboratory of Life Science and Biomolecular Engineering, Japan Tobacco, Inc, Yokohama, Japan
    Exp Cell Res 237:207-16. 1997
    ..Here, I present evidence that cystine is essential for the maintenance of normal-sized nuclear bodies: Cystine deficiency induces the formation of ..
  92. pmc System xc⁻ cystine/glutamate antiporter: an update on molecular pharmacology and roles within the CNS
    Richard J Bridges
    Center for Structural and Functional Neuroscience, Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, Montana 59812, USA
    Br J Pharmacol 165:20-34. 2012
    System x(c)(-) is an amino acid antiporter that typically mediates the exchange of extracellular l-cystine and intracellular L-glutamate across the cellular plasma membrane...
  93. ncbi Inhibition of xc⁻ transporter-mediated cystine uptake by sulfasalazine analogs
    Krupa Shukla
    Department of Neurology, Johns Hopkins University, Baltimore, MD 21205, USA
    Bioorg Med Chem Lett 21:6184-7. 2011
    A series of sulfasalazine analogs were synthesized and tested for their ability to block cystine-glutamate antiporter system xc⁻ using L-[(14)C]cystine as a substrate...
  94. ncbi Stone clustering of patients with cystine urinary stone formation
    Rajveer S Purohit
    Department of Urology, University of California, San Francisco, School of Medicine, San Francisco, California 94143 0738, USA
    Urology 63:630-4; discussion 634-5. 2004
    To explore the history of symptomatic cystine stone formation. Cystinuria is a genetic defect that may result in the formation of recurrent cystine calculi.
  95. ncbi Inhibition of Na(+)-dependent transporters in cystine-loaded human renal cells: electrophysiological studies on the Fanconi syndrome of cystinosis
    Ibrahim Cetinkaya
    Department of Pediatrics, University Children s Hospital Muenster, Muenster, Germany
    J Am Soc Nephrol 13:2085-93. 2002
    ..A defective lysosomal transporter, cystinosin, results in intralysosomal accumulation of cystine. Loading cells with cystine dimethyl ester (CDME) is the only available model for this disease...
  96. ncbi Design and synthesis of potent cystine-free cyclic hexapeptide agonists at the human urotensin receptor
    Shane Foister
    Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Org Lett 8:1799-802. 2006
    ..Further development led to a hexapeptide agonist with nanomolar affinity (2.8 nM)...
  97. ncbi Urinary felinine excretion in intact male cats is increased by dietary cystine
    Wouter H Hendriks
    Animal Nutrition Group, Department of Animal Sciences, Wageningen University, Wageningen, The Netherlands
    Br J Nutr 100:801-9. 2008
    ..The objective of the present study was to determine if additional cystine and/or dietary N would increase felinine and N-acetylfelinine excretion by intact male cats fed a low-protein(LP) ..
  98. pmc Effects of a novel cystine-based glutathione precursor on oxidative stress in vascular smooth muscle cells
    Indrani Sinha-Hikim
    Dept of Medicine, Charles Drew Univ, 1731 E 120th St, Los Angeles, CA 90059, USA
    Am J Physiol Cell Physiol 299:C638-42. 2010
    ..We investigated the effect of three glutathione (GSH) precursors: N-acetyl-cysteine (NAC), cystine as the physiological carrier of cysteine in GSH with added selenomethionine (F1), and NAC fortified with ..
  99. ncbi Regulation of the system x(C)- cystine/glutamate exchanger by intracellular glutathione levels in rat astrocyte primary cultures
    Todd Michael Seib
    CSFN, Center for Structural and Functional Neuroscience, Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, Montana 59812, USA
    Glia 59:1387-401. 2011
    The system x(C)- (Sx(C)-) transporter functions to mediate the exchange of extracellular cystine (L-Cys(2)) and intracellular glutamate (L-Glu)...
  100. ncbi The xc- cystine/glutamate antiporter as a potential therapeutic target for small-cell lung cancer: use of sulfasalazine
    Jun Guan
    Department of Cancer Endocrinology, BC Cancer Agency, Research Centre, Vancouver, BC, Canada
    Cancer Chemother Pharmacol 64:463-72. 2009
    To determine whether the xc- cystine transporter could be a useful therapeutic target for small-cell lung cancer (SCLC).
  101. ncbi The interactions between cysteamine, cystine and cumulus cells increase the intracellular glutathione level and developmental capacity of goat cumulus-denuded oocytes
    Ping Zhou
    Laboratory for Animal Reproduction and Embryology, College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Taian City 271018, Shandong Province, People s Republic of China
    Reproduction 135:605-11. 2008
    To improve in vitro maturation (IVM) of denuded oocytes (DOs), we observed the interactive effects of cysteamine, cystine and cumulus cells on the glutathione (L-gamma-glutamyl-L-cysteinyl-glycine; GSH) level and developmental capacity ..

Research Grants62

  1. Cyr61/CCN1-Induced Angiogenesis and Vasculogenesis in the Retina
    Brahim Chaqour; Fiscal Year: 2010
    ..the von Willebrand factor type C (vWFC) repeat, the thrombospondin type I (TSP1) repeat and a C-terminal (CT) cystine-knot motif...
  2. Lentiviral-transduced hematopoictic stem cell transplantation for cystinosis
    Stephanie Cherqui; Fiscal Year: 2013
    ..by applicant): Cystinosis is a metabolic hereditary disease characterized by intracellular accumulation of cystine. Affected individuals typically present with proximal tubulopathy (Fanconi syndrome) before one year of age and ..
  3. ROS, Redox Regulation and Novel Targets for Cancer Therapy
    Peng Huang; Fiscal Year: 2013
    ..drug resistance through enhancing GSH synthesis mediated by an intercellular metabolic communication involving cystine->cysteine conversion and shuttling between the two cell compartments...
  4. METABOLIC SIGNAL TRANSDUCTION IN ADIPOCYTES
    Orian S Shirihai; Fiscal Year: 2013
    ..by cells and link all tissues of the body: couples include the thiol (SH/SS) ratios, reflected in the cysteine/cystine and GSH/GSSG ratios, the mitochondrial redox state reflected in the ss-hydroxybutyrate (ss-OHB)/ acetoacetate (..
  5. Soft Metal, Disulfide, and Cysteine Stresses in Escherichia coli
    James A Imlay; Fiscal Year: 2013
    ..provided by applicant): The goals of this study are to investigate the mechanisms by which soft metals, cystine import, and cysteine accumulation can perturb the fitness of Escherichia coli...
  6. Identification of novel system xc- inhibitors
    BARBARA STAUCH SLUSHER; Fiscal Year: 2012
    ..is to develop a 96-well plate screening assay that will allow screening for small molecule inhibitors of the cystine-glutamate antiporter, also known as system Xc-...
  7. Endogenous and exogenous protection of the BBB in stroke
    Richard F Keep; Fiscal Year: 2013
    ..We have also shown that stroke-related factors cause a marked increase in the expression of the cystine/glutamate exchanger (system xc-), a regulator of intracellular glutathione, in cerebral endothelial cells...
  8. Structure of sclerostin protein complexes
    Rajiv Kumar; Fiscal Year: 2012
    ..is to investigate at the atomic level, the mechanism of action of sclerostin, an osteocyte-derived, secreted, cystine-knot protein that inhibits bone formation by examining how sclerostin interacts with proteins that play an ..
  9. Kidney-targeted gene delivery for cystinosis
    Stephanie Cherqui; Fiscal Year: 2012
    ..by applicant): Cystinosis is a metabolic hereditary disease characterized by intracellular accumulation of cystine. Affected individuals typically present with proximal tubulopathy (Fanconi syndrome) before one year of age and ..
  10. Toxicology studies for gene-modified stem cell transplantation for cystinosis
    Stephanie Cherqui; Fiscal Year: 2013
    ..by applicant): Cystinosis is a metabolic hereditary disease characterized by intracellular accumulation of cystine. Affected individuals typically present with proximal tubulopathy before one year of age and eventually progress ..
  11. Role of System xc in Asbestos Induced Autoimmune Responses
    JEAN COOPER PFAU; Fiscal Year: 2010
    ..System xc- protects cells from oxygen radicals by importing cystine, which is subsequently made into glutathione (GSH), a critical cell antioxidant...
  12. Oxidant Stress: Is it a biomarker of disease progression and response to therapy
    Jesse Roman; Fiscal Year: 2010
    ..oxidized redox potential, as determined by oxidation of one or more of the thiol disulfide couples cysteine and cystine (Cys/CySS) and glutathione and glutathione disulfide (GSH/GSSG), will be the ones to benefit from anti-oxidant ..
  13. Aging related susceptibility to lung injury - remodeling and oxidative stress
    Jesse Roman; Fiscal Year: 2012
    ..It has been shown that elderly animals (and humans) manifest oxidation of their plasma cysteine/cystine redox potential...
  14. Phase II Trial of Tiopronin in Aneurysmal Subarachnoid Hemorrhage
    EDWARD SANDER CONNOLLY; Fiscal Year: 2011
    ..It is the intention of this study to examine the effect of tiopronin, an FDA approved drug for the indication of cystine kidney stones, on clinical outcome and levels of the neurotoxin 3AP in the body following aSAH...
  15. Mesenchymal Stem Cell Therapy for Corneal Cystinosis
    JENNIFER LYNNE SIMPSON; Fiscal Year: 2013
    ..Cystinosis is a rare lysosomal storage disease caused by a defect in the cystine lysosomal transporter cystinosin (CTNS) that leads to cystine crystal formation in various tissues and organs ..
  16. Oxidative Stress and Pathological Glutamate Release in Stroke
    Alexander A Mongin; Fiscal Year: 2013
    ..has identified three redox-sensitive glutamate release pathways: volume-regulated anion channels (VRAC), the cystine/glutamate antiporter (xCT), and the connexin hemichannels (Cxs)...
  17. Role of System xc- in Addiction: Developing &Phenotyping a Slc7a11 knockout rat
    Aron M Geurts; Fiscal Year: 2013
    ..Increasing system xc activity by direct infusion of cystine into the brain or systemic administration of a cysteine prodrug (e.g...
  18. Polarity of Redox Control and Risk of Injury in the Alveolar Epithelium
    Dean P Jones; Fiscal Year: 2010
    ..the epithelial lining fluid (ELF) and plasma for reduced and oxidized glutathione (GSH/GSSG) and cysteine and cystine (Cys/CySS). Further, these thiol pairs are not in equilibrium in either compartment...
  19. Ethanol Dependence, Drinking &Mechanisms Regulating Accumbal Glutamate Activity
    Vorani Ramachandra; Fiscal Year: 2013
    ..Amino Acid Transporter 2 (EAAT2), while the main contributor to extracellular glutamate in this region is the cystine-glutamate exchanger (system x{c}), Western blot analyses will be performed to evaluate surface expression of ..
  20. Genetic and pharmacological manipulation of system xc in pancreatic cancer
    MICHAEL ALEXANDER BADGLEY; Fiscal Year: 2013
    ..causes an iron-dependent form of oxidative cell death, termed "ferroptosis," through the inhibition of a cystine-glutamate antiporter named system xc- [5]...
  21. Regulation of Gene Expression During Stress
    Maria Hatzoglou; Fiscal Year: 2013
    ..acid uptake in the regulation of mRNA translation and (iii) the mechanism via which increased methionine and cystine uptake contribute to protection of [unreadable] cells from ER stress-induced apoptosis...
  22. Mayo Clinic Urology O'Brien Research Center
    John C Lieske; Fiscal Year: 2012
    ..g., uric acid vs. cystine vs. struvite vs. calcium-based stones) and provide accurate quantification of stone burden...
  23. Amino Acid Transport and the Biology of Human Gliomas
    Harald W Sontheimer; Fiscal Year: 2013
    ..It is hypothesized that glutamate is released as an obligatory by-product of cystine uptake into tumor cells via the system xc- (SXC) cystine-glutamate exchanger...
  24. A Novel Viral Membrane Fusion Triggering Mechanism
    Judith M White; Fiscal Year: 2013
    ..The second is that cystinosin, a cystine transporter, maintains the reducing environment in LE/Lys...
  25. Targeting System Xc- for the Treatment of Schizophrenia
    CHAD EDWARD BEYER; Fiscal Year: 2013
    ..Specifically, cystine-glutamate exchange (system xc-) appears to be altered in schizophrenic patients, and we have shown previously in ..
  26. Targeting System Xc- for the Treatment of Addiction
    John R Mantsch; Fiscal Year: 2010
    ..Towards this end, drug-induced changes in glutamate release from cystine-glutamate antiporters have been linked to pathological alterations in neural transmission and normalizing cystine-..
  27. Fluorescent-based Probes for the Glutamate/Cystine Exchanger System Xc-
    Nicholas R Natale; Fiscal Year: 2010
    ..that is becoming increasingly recognized as a relevant physiological and therapeutic target, the glutamate/cystine transporter system Xc- (SXc-)...
  28. Structure and Function of Neurotransmitter Transporters
    James E Gouaux; Fiscal Year: 2013
    ..In other cases, such as with the glutamate/cystine exchanger, the transporter protein obligatorily exchanges one substrate (glutamate) for another (cystine);these ..
  29. EFFECT OF AGING ON INTERORGAN GLUTATHIONE HOMEOSTASIS
    Murad Ookhtens; Fiscal Year: 1999
    ..We will inject 35S-labeled GSH, cysteine (CYSH) or cystine (CYSS) i.v...
  30. Functional PET Imaging of Oxidative Stress
    JACK MATHEW WEBSTER; Fiscal Year: 2013
    ..team has already demonstrated this vital milestone of transporter promiscuity and demonstrated in vivo uptake of cystine in tumors validated for transporter activity...
  31. Regulation of System xc- by Interleukin-1 beta
    NICOLE ALYSE JACKMAN; Fiscal Year: 2010
    ..Overall, the long-term objective of this project is to better understand how IL-1beta regulates the cystine-glutamate (system xc) transporter...
  32. Contributions of Glial Glutamate Transport and Transmission to Drug Abuse
    KATHRYN JOANNA REISSNER; Fiscal Year: 2013
    ..chronic exposure to cocaine are decreased function and protein expression of the catalytic subunit of the cystine-glutamate exchanger (xCT) and high affinity glial glutamate transporter GLT-1, two integral regulators of ..
  33. Contributions of Glial Glutamate Transport and Transmission to Drug Abuse
    KATHRYN JOANNA REISSNER; Fiscal Year: 2013
    ..chronic exposure to cocaine are decreased function and protein expression of the catalytic subunit of the cystine-glutamate exchanger (xCT) and high affinity glial glutamate transporter GLT-1, two integral regulators of ..
  34. Receptor-mediated effects of ethanol in lung tissue injury and repair
    Jesse Roman; Fiscal Year: 2013
    ..in lung fibroblasts and 2) that ethanol-induced oxidant stress (through oxidation of the extracellular cysteine/cystine redox potential) might directly activate nAChRs...
  35. Regulation of System xc- by Interleukin-1Beta
    Nicole Jackman; Fiscal Year: 2009
    ..Overall, the long-term objective of this project is to better understand how IL-i[unreadable] regulates the cystine-glutamate (system xc-) transporter...
  36. IL-1 in Protection and Injury
    Sandra J Hewett; Fiscal Year: 2013
    ..During the last grant period our laboratory demonstrated that astrocyte-mediated alterations in system xc- (cystine/glutamate antiporter) activity contributes to the development and progression of inflammatory (IL-1beta-enhanced) ..
  37. Constructing a Conditional Slc7a11 (xCT) Null Mouse
    Sandra J Hewett; Fiscal Year: 2012
    ..using an in vitro model of the ischemic penumbra - that astrocyte-mediated alterations in system xc- (cystine/glutamate antiporter) contribute to the development and progression of inflammatory (IL-12-mediated) hypoxic ..
  38. Cocaine, Opoids and Drug Abuse
    Peter W Kalivas; Fiscal Year: 2013
    ..2 evaluates the enduring restoration by NAC in the level and function of nonsynaptic glutamate release via the cystine-glutamate exchanger and glial glutamate uptake...
  39. Human Choriogonadotropin Signaling in Cell Proliferation
    MICHAEL HUDECKI; Fiscal Year: 2003
    ..All of them contain cystine knot motif and have been implicated in the development of a variety of tumors...
  40. Oral delivery of peptides targeting intracellular protein-protein interactions
    Mark W Nowak; Fiscal Year: 2012
    ..A novel approach to overcome these barriers is to use cystine-knot microprotein (CKM) technology as a vehicle to deliver bioactive peptides...
  41. Histotripsy for Urinary Stone Comminution
    Timothy L Hall; Fiscal Year: 2013
    ..Large stones (>20 mm diameter), stones of difficult composition (i.e. cystine), and stones located in the lower pole all have worse outcomes further discouraging treatment with SWL...
  42. A Controlled Trial of NAC for Cocaine Dependence
    Robert Malcolm; Fiscal Year: 2009
    ..is a plasma membrane-bound sodium dependent anionic amino acid transporter that exchanges extra cellular cystine for intra cellular glutamate...
  43. Glutamate Transporters and Cocaine Seeking
    Lori A Knackstedt; Fiscal Year: 2013
    ..System xC-,which exchanges one extracellular cystine molecule for one intracellular glutamate molecule, has been found to account for the majority of basal ..
  44. Structure and Function of Neurotransmitter Transporters
    JAMES GOUAUX; Fiscal Year: 2009
    ..In other cases, such as with the glutamate/cystine exchanger, the transporter protein obligatorily exchanges one substrate (glutamate) for another (cystine);these ..
  45. HUMAN PHAGOCYTES, OXYGEN METABOLITES AND INFLAMMATION
    Stephen Weiss; Fiscal Year: 2002
    ..Third, to characterize the role of the macrophage vacuolar-type H+-ATPase and L-cystine transport systems in generating an acidic and reducing extracellular environment permissive for cysteine ..
  46. STRUCTURE/FUNCTION RELATIONSHIPS OF HUMAN THYROTROPIN
    Bruce Weintraub; Fiscal Year: 2000
    ..until our recent observations, there had not been reports for any glycoprotein hormone or any member of the cystine knot growth factor superfamily of such analogs with major increases in receptor binding affinity or in vitro ..
  47. Diagnosis of Crystalopathies via Raman Spectroscopy
    Ozan Akkus; Fiscal Year: 2006
    ..dihydrate, hydroxyapatite, octacalcium phosphate, tricalcium phosphate, calcium oxalate, cholesterol, cystine and xanthine will be mixed with healthy synovial fluid samples at various concentrations and these mixtures will ..
  48. SYNTHETIC STUDIES OF PROTEIN STABILITY AND FOLDING
    George Barany; Fiscal Year: 2001
    ..During the first period of support, it was shown that replacement of cystine crosslinks in BPTI by paired alpha-amino-n-butyric acid (Abu) isosteres provides proteins which, under mild ..
  49. DIETARY PROTEIN INTAKE & HUMAN PROTEIN METABOLISM
    Vernon Young; Fiscal Year: 1991
    ..indispensable, amino acids- these are (i) the proline, arginine and ornithine "triad" (11) tyrosine and (iii) cystine; (b) explore the consequences of alterations in the dietary intake of total nitrogen and/or specific amino acids ..
  50. CHEMISTRY OF INHIBIN AND RELATED HORMONES
    DARRELL WARD; Fiscal Year: 1990
    ..g. reduciton and alkylation of the cystine residues, followed by subunit separation in the case of the glycopeptide study)...
  51. RAC 1 SIGNALING PATHWAY IN AIRWAY SMOOTH MUSCLE
    MARC HERSHENSON; Fiscal Year: 2002
    ..We will also measure the effects of antioxidants (ebselen), N-acetyl cystine and catalase) and NADPH oxidase inhibitors (diphenylene iodonium and N-terminal fragment of p67/phox) on Racl-..
  52. Striatal Glutamate Homeostasis and Cocaine Relapse
    Lori Knackstedt; Fiscal Year: 2009
    ..System xc-, which exchanges one extracellular cystine molecule for one intracellular glutamate molecule, has been found to account for the majority of basal ..
  53. INDUCERS OF MATURATION OF RENAL AMINO ACID TRANSPORT
    Russell Chesney; Fiscal Year: 1980
    ..1) a 3% taurine diet that allows one to give a high taurine load and (2) a diet deficient in methiionine, cystine, cysteine and taurine...
  54. CONSTRAINED HIV1 GP41 ELDKWA PEPTIDES FOR AIDS VACCINES
    John Taylor; Fiscal Year: 2000
    ..A series of cystine-bridge peptides designed to favor beta-sheets, beta-turns or beta-budges will be explored, since these ..
  55. ANTICYSTINOTIC AGENTS, RESEARCH AND DEVELOPMENT
    MAXIMILLIAN VON STRANDTMANN; Fiscal Year: 1992
    ..is a rare, inborn, fatal, metabolic disorder resulting from the inability of the lysosomal tissues to clear cystine. Cystinosis is presently controlled by administration of cysteamine or phosphocysteamine...
  56. MECHANISMS OF INHERITED MEMBRANE TRANSPORT DISORDERS
    Stanton Segal; Fiscal Year: 1992
    ..These are: Project 1, Cystinuria and the Nature of the Renal Cystine-Lysine Transport System, Dr...
  57. ND GENE IN RETINAL DYSPLASIA AND CELL DEATH
    Katherine Sims; Fiscal Year: 1999
    ..Recent molecular modeling suggests norrin may have tertiary structural features seen in members of the cystine knot growth factor family...
  58. Glutamate-Mediated Attenuation of Cocaine Craving
    SHELLEY AMEN; Fiscal Year: 2009
    ..This proposal seeks to develop the preclinical findings that the cystine/glutamate antiporter may restore basal (non-drug) tone of glutamate surrounding neurons in drug reward-associated ..
  59. EXPERIMENTAL CYSTINE STORAGE MODEL OF FANCONI SYNDROME
    John Foreman; Fiscal Year: 1990
    ..The biochemical hallmark of this is excessive intracellular storage of cystine, although the relationship between this and the renal tubule dysfunction is unknown...
  60. MOLECULAR MECHANISMS OF PERINATAL WHITE MATTER INJURY
    STEPHEN BACK; Fiscal Year: 2000
    ..Glutamate toxicity can be prevented by cystine, a precursor for glutathione...
  61. REGULATION OF PHOSPHOPROTEIN PHOSPHATASES
    DAVID BRAUTIGAN; Fiscal Year: 1990
    ..Active and inactive forms of the phosphatase will be analyzed by diagonal electrophoresis of cystine peptides...
  62. A PROGRAM FOR DEVELOPMENT OF NEW ANTITUMOR ENZYMES
    JOSEPH ROBERTS; Fiscal Year: 1980
    ..and those isolated from soil by the enrichment culture technique for production of the following enzymes: (a) a cystine-degrading enzyme capable of depleting plasma cystine in vivo; (b) enzymes which will attack the polyamines (..