Summary: Glycosphingolipids which contain as their polar head group a trisaccharide (galactose-galactose-glucose) moiety bound in glycosidic linkage to the hydroxyl group of ceramide. Their accumulation in tissue, due to a defect in ceramide trihexosidase, is the cause of angiokeratoma corporis diffusum (FABRY DISEASE).

Top Publications

  1. Clarke J, West M, Bultas J, Schiffmann R. The pharmacology of multiple regimens of agalsidase alfa enzyme replacement therapy for Fabry disease. Genet Med. 2007;9:504-9 pubmed
    ..However, because plasma Gb3 is not a validated surrogate of disease severity in Fabry disease, further clinical study will be required to determine the optimal dosing regimen for providing maximal clinical benefit. ..
  2. Ling H, Boodhoo A, Hazes B, Cummings M, Armstrong G, Brunton J, et al. Structure of the shiga-like toxin I B-pentamer complexed with an analogue of its receptor Gb3. Biochemistry. 1998;37:1777-88 pubmed
    ..The structural model is consistent with data from site-directed mutagenesis and binding of carbohydrate analogues, and allows the rational design of therapeutic Gb3 analogues that block the attachment of toxin to cells. ..
  3. Shu L, Murphy H, Cooling L, Shayman J. An in vitro model of Fabry disease. J Am Soc Nephrol. 2005;16:2636-45 pubmed
    ..These cells provide a useful model for comparing pharmacologic agents used for glycolipid reduction. ..
  4. Yosief H, Iyer S, Weiss A. Binding of Pk-trisaccharide analogs of globotriaosylceramide to Shiga toxin variants. Infect Immun. 2013;81:2753-60 pubmed publisher
    ..To our knowledge, this is the first study examining the minimum number of Pk analogs required for effective binding and the first report documenting the role of the A subunit in influencing Stx2 binding. ..
  5. Falguières T, Maak M, Von Weyhern C, Sarr M, Sastre X, Poupon M, et al. Human colorectal tumors and metastases express Gb3 and can be targeted by an intestinal pathogen-based delivery tool. Mol Cancer Ther. 2008;7:2498-508 pubmed publisher
  6. Vylet al P, Hulkova H, Zivná M, Berna L, Novak P, Elleder M, et al. Abnormal expression and processing of uromodulin in Fabry disease reflects tubular cell storage alteration and is reversible by enzyme replacement therapy. J Inherit Metab Dis. 2008;31:508-17 pubmed publisher
    ..Extended comparative studies of UMOD expression in kidney specimens obtained during individual types of therapies are therefore of great interest. ..
  7. Kovbasnjuk O, Mourtazina R, Baibakov B, Wang T, Elowsky C, Choti M, et al. The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer. Proc Natl Acad Sci U S A. 2005;102:19087-92 pubmed
    ..These data demonstrate the appearance of a subpopulation of Gb(3) containing epithelial cells in the metastatic stage of human colon cancer and suggest their possible role in colon cancer invasiveness. ..
  8. Togawa T, Kodama T, Suzuki T, Sugawara K, Tsukimura T, Ohashi T, et al. Plasma globotriaosylsphingosine as a biomarker of Fabry disease. Mol Genet Metab. 2010;100:257-61 pubmed publisher
    ..The plasma lyso-Gb3 level in the Fabry patient who had received ERT was elevated at the baseline and fell more dramatically on ERT than that of Gb3. Plasma lyso-Gb3 could thus be a potential biomarker of Fabry disease. ..
  9. Malyukova I, Murray K, Zhu C, Boedeker E, Kane A, Patterson K, et al. Macropinocytosis in Shiga toxin 1 uptake by human intestinal epithelial cells and transcellular transcytosis. Am J Physiol Gastrointest Liver Physiol. 2009;296:G78-92 pubmed publisher
    ..These observations provide new insights into the understanding of Shiga toxin contribution to enterohemorrhagic E. coli-related intestinal and systemic diseases. ..

More Information


  1. Park E, Choi J, Park J, Lee M, Park H, Jung S. Expression of genes and their responses to enzyme replacement therapy in a Fabry disease mouse model. Int J Mol Med. 2009;24:401-7 pubmed
    ..Furthermore, these genes are promising targets for developing biomarkers for monitoring disease progression and therapeutic efficacy in patients with Fabry disease. ..
  2. Eitzman D, Bodary P, Shen Y, Khairallah C, Wild S, Abe A, et al. Fabry disease in mice is associated with age-dependent susceptibility to vascular thrombosis. J Am Soc Nephrol. 2003;14:298-302 pubmed
  3. Schumann J, Facciotti F, Panza L, Michieletti M, Compostella F, Collmann A, et al. Differential alteration of lipid antigen presentation to NKT cells due to imbalances in lipid metabolism. Eur J Immunol. 2007;37:1431-41 pubmed
    ..Based on these results, the impact of lipid accumulation should be generally considered in the interpretation of immunological deficiencies found in mice suffering from lipid metabolic disorders. ..
  4. Young E, Mills K, Morris P, Vellodi A, Lee P, Waldek S, et al. Is globotriaosylceramide a useful biomarker in Fabry disease?. Acta Paediatr Suppl. 2005;94:51-4; discussion 37-8 pubmed
    ..Additionally, Gb3 cannot be used to monitor the response to treatment in patients who initially have normal plasma and urine concentrations of this glycolipid. ..
  5. Linthorst G, Hollak C, Donker Koopman W, Strijland A, Aerts J. Enzyme therapy for Fabry disease: neutralizing antibodies toward agalsidase alpha and beta. Kidney Int. 2004;66:1589-95 pubmed
    ..Further studies on the clinical implications of alpha-Gal A antibodies are essential. ..
  6. Ramegowda B, Samuel J, Tesh V. Interaction of Shiga toxins with human brain microvascular endothelial cells: cytokines as sensitizing agents. J Infect Dis. 1999;180:1205-13 pubmed
    ..HBMECs did not produce IL-1beta and produced only trace amounts of TNF-alpha when stimulated with purified Stx1 in vitro. ..
  7. Cheng L, Ueno A, Cho S, Im J, Golby S, Hou S, et al. Efficient activation of Valpha14 invariant NKT cells by foreign lipid antigen is associated with concurrent dendritic cell-specific self recognition. J Immunol. 2007;178:2755-62 pubmed
    ..Thus, CD1d-dependent potentiation by DCs may be crucial for iNKT cell-mediated immunity against infectious agents. ..
  8. Abe A, Gregory S, Lee L, Killen P, Brady R, Kulkarni A, et al. Reduction of globotriaosylceramide in Fabry disease mice by substrate deprivation. J Clin Invest. 2000;105:1563-71 pubmed
    ..These data suggest that Fabry disease may be amenable to substrate deprivation therapy. ..
  9. Kojima Y, Fukumoto S, Okajima T, Wiels J, Yokoyama K, Suzuki Y, et al. Molecular cloning of globotriaosylceramide/CD77 synthase, a glycosyltransferase that initiates the synthesis of globo series glycosphingolipids. J Biol Chem. 2000;275:15152-6 pubmed
    ..Since Gb3/CD77 synthase initiates the synthesis of globo series glycolipids, the isolation of this cDNA will make possible further investigations into the function of its important series of glycolipids. ..
  10. Hughes D. Early therapeutic intervention in females with Fabry disease?. Acta Paediatr. 2008;97:41-7 pubmed publisher
    ..Any strategy for early therapy should also balance future advantages against any impact on quality of life. ..
  11. Soltyk A, Mackenzie C, Wolski V, Hirama T, Kitov P, Bundle D, et al. A mutational analysis of the globotriaosylceramide-binding sites of verotoxin VT1. J Biol Chem. 2002;277:5351-9 pubmed
    ..Our data show that the interaction of verotoxin with the Gb(3) trisaccharide is highly context dependent and that a membrane environment is required for biologically relevant studies of the interaction. ..
  12. Stricklett P, Hughes A, Ergonul Z, Kohan D. Molecular basis for up-regulation by inflammatory cytokines of Shiga toxin 1 cytotoxicity and globotriaosylceramide expression. J Infect Dis. 2002;186:976-82 pubmed
    ..Thus, inflammatory cytokine up-regulation of the sensitivity of HBECs to Stx-1 is the result of up-regulation, most likely via transcription, of the activities of 3 enzymes involved in Gb3 synthesis. ..
  13. Obata F, Tohyama K, Bonev A, Kolling G, Keepers T, Gross L, et al. Shiga toxin 2 affects the central nervous system through receptor globotriaosylceramide localized to neurons. J Infect Dis. 2008;198:1398-406 pubmed publisher
    ..In this article, we propose that the neuron is a primary target of Stx2, affecting neuronal function and leading to paralysis. ..
  14. Falguières T, Mallard F, Baron C, Hanau D, Lingwood C, Goud B, et al. Targeting of Shiga toxin B-subunit to retrograde transport route in association with detergent-resistant membranes. Mol Biol Cell. 2001;12:2453-68 pubmed
    ..Our data thus provide first evidence for a role of lipid asymmetry in membrane sorting at the interface between early endosomes and the trans-Golgi network. ..
  15. De Rosa M, Ackerley C, Wang B, Ito S, Clarke D, Lingwood C. Inhibition of multidrug resistance by adamantylgb3, a globotriaosylceramide analog. J Biol Chem. 2008;283:4501-11 pubmed
    ..Thus, a functional interplay between membrane Gb3 and MDR1 provides a more physiologically based approach to MDR1 regulation to increase the bioavailability of chemotherapeutic drugs. ..
  16. Distler U, Souady J, Hülsewig M, Drmić Hofman I, Haier J, Friedrich A, et al. Shiga toxin receptor Gb3Cer/CD77: tumor-association and promising therapeutic target in pancreas and colon cancer. PLoS ONE. 2009;4:e6813 pubmed publisher
  17. Lingwood C. Verotoxin/globotriaosyl ceramide recognition: angiopathy, angiogenesis and antineoplasia. Biosci Rep. 1999;19:345-54 pubmed
    ..Thus VT may have both a direct and indirect antineoplastic potential. VT has proved highly effective in a xenograft cancer model and the possible therapeutic use of VT is discussed. ..
  18. Schiffmann R, Waldek S, Benigni A, Auray Blais C. Biomarkers of Fabry disease nephropathy. Clin J Am Soc Nephrol. 2010;5:360-4 pubmed publisher
    ..Standard scoring of all pathologic aspects of kidney biopsies may also be a promising way to assess the effect of therapy. ..
  19. Godfrey D, McConville M, Pellicci D. Chewing the fat on natural killer T cell development. J Exp Med. 2006;203:2229-32 pubmed
    ..This suggests that lysosomal storage diseases (LSDs) in general, rather than one specific defect, can disrupt CD1d antigen presentation, leading to impaired development of NKT cells. ..
  20. Schweppe C, Bielaszewska M, Pohlentz G, Friedrich A, Büntemeyer H, Schmidt M, et al. Glycosphingolipids in vascular endothelial cells: relationship of heterogeneity in Gb3Cer/CD77 receptor expression with differential Shiga toxin 1 cytotoxicity. Glycoconj J. 2008;25:291-304 pubmed publisher
    ..This deficiency, resulting in the accumulation of Gb3Cer in EA.hy 926 cells, represents the most prominent molecular reason that underlies the different Stx1 sensitivities of HBMECs and EA.hy 926 endothelial cells. ..
  21. Salhia B, Rutka J, Lingwood C, Nutikka A, van Furth W. The treatment of malignant meningioma with verotoxin. Neoplasia. 2002;4:304-11 pubmed
    ..VT1 treatment of MM is effective in our orthotopic xenograft model, and warrants further exploration as a potential treatment for these highly anaplastic and aggressive neoplasms. ..
  22. Ergonul Z, Hughes A, Kohan D. Induction of apoptosis of human brain microvascular endothelial cells by shiga toxin 1. J Infect Dis. 2003;187:154-8 pubmed
    ..TNF greatly increased Stx-1 cytotoxicity, primarily through induction of apoptosis, in HBEC. ..
  23. Binnington B, Lingwood D, Nutikka A, Lingwood C. Effect of globotriaosyl ceramide fatty acid alpha-hydroxylation on the binding by verotoxin 1 and verotoxin 2. Neurochem Res. 2002;27:807-13 pubmed
    ..Unexpectedly, the VT1 Kd for Gb3 was found to decrease as an inverse function of the Gb3 concentration. This shows that glycolipids have "nonclassical" receptor properties. ..
  24. Johansson D, Kosovac E, Moharer J, Ljuslinder I, Brannstrom T, Johansson A, et al. Expression of verotoxin-1 receptor Gb3 in breast cancer tissue and verotoxin-1 signal transduction to apoptosis. BMC Cancer. 2009;9:67 pubmed publisher
    ..The high specificity and apoptosis-inducing properties of verotoxin-1 indicates that the toxin potentially may be used for treatment of Gb3-expressing breast cancer. ..
  25. Germain D, Waldek S, Banikazemi M, Bushinsky D, Charrow J, Desnick R, et al. Sustained, long-term renal stabilization after 54 months of agalsidase beta therapy in patients with Fabry disease. J Am Soc Nephrol. 2007;18:1547-57 pubmed
    ..Long-term agalsidase beta therapy stabilizes renal function in patients without renal involvement at baseline, maintains reduction of plasma GL-3, and sustains GL-3 clearance in capillary endothelial cells and multiple renal cell types. ..
  26. Raa H, Grimmer S, Schwudke D, Bergan J, Walchli S, Skotland T, et al. Glycosphingolipid requirements for endosome-to-Golgi transport of Shiga toxin. Traffic. 2009;10:868-82 pubmed publisher
    ..In contrast, Fumonisin B(1) affected the amount and composition of sphingomyelin and glycolipids and altered the profiles of phospholipids and plasmalogens. ..
  27. Meisen I, Friedrich A, Karch H, Witting U, Peter Katalinic J, Muthing J. Application of combined high-performance thin-layer chromatography immunostaining and nanoelectrospray ionization quadrupole time-of-flight tandem mass spectrometry to the structural characterization of high- and low-affinity binding ligands of Shiga. Rapid Commun Mass Spectrom. 2005;19:3659-65 pubmed
  28. Gupta S, Ries M, Kotsopoulos S, Schiffmann R. The relationship of vascular glycolipid storage to clinical manifestations of Fabry disease: a cross-sectional study of a large cohort of clinically affected heterozygous women. Medicine (Baltimore). 2005;84:261-8 pubmed
    ..Useful outcome measures for assessment of specific therapies need to be developed. Studies limited to homogeneously affected subjects may be possible. ..
  29. Ortiz A, Oliveira J, Wanner C, Brenner B, Waldek S, Warnock D. Recommendations and guidelines for the diagnosis and treatment of Fabry nephropathy in adults. Nat Clin Pract Nephrol. 2008;4:327-36 pubmed publisher
    ..These organ-specific guidelines could be easier to implement than general guidelines, provided they are used in the context of an overall multisystem care approach. ..
  30. Chark D, Nutikka A, Trusevych N, Kuzmina J, Lingwood C. Differential carbohydrate epitope recognition of globotriaosyl ceramide by verotoxins and a monoclonal antibody. Eur J Biochem. 2004;271:405-17 pubmed
    ..Heterogeneity in glomerular globotriaosylceramide expression may play a significant (cholesterol-dependent?) role in determining renal pathology following verotoxemia. ..
  31. Schiffmann R, Murray G, Treco D, Daniel P, Sellos Moura M, Myers M, et al. Infusion of alpha-galactosidase A reduces tissue globotriaosylceramide storage in patients with Fabry disease. Proc Natl Acad Sci U S A. 2000;97:365-70 pubmed
    ..Taken together, these results suggest that enzyme replacement is likely to be an effective therapy for patients with this metabolic disorder. ..
  32. Hughes A, Ergonul Z, Stricklett P, Kohan D, Ergonal Z. Molecular basis for high renal cell sensitivity to the cytotoxic effects of shigatoxin-1: upregulation of globotriaosylceramide expression. J Am Soc Nephrol. 2002;13:2239-45 pubmed
    ..These studies suggest that high renal Gb3 expression is due to enhanced GalT6 gene transcription and reduced alpha-galactosidase gene transcription and occur despite relatively low GalT2 activity. ..
  33. Kovbasnjuk O, Edidin M, Donowitz M. Role of lipid rafts in Shiga toxin 1 interaction with the apical surface of Caco-2 cells. J Cell Sci. 2001;114:4025-31 pubmed
    ..Although disruption of lipid rafts by cholesterol depletion did not affect the amount of bound Shiga toxin 1 B-subunit, lipid rafts are necessary for toxin uptake across the apical membrane of Caco-2 cells. ..
  34. Ries M, Gupta S, Moore D, Sachdev V, Quirk J, Murray G, et al. Pediatric Fabry disease. Pediatrics. 2005;115:e344-55 pubmed
    ..We have identified important, potentially correctable or preventable, outcome measures for future therapeutic trials. Prevention of complications involving major organs should be the goal for long-term specific therapy. ..
  35. Thurberg B, Fallon J, Mitchell R, Aretz T, Gordon R, O Callaghan M. Cardiac microvascular pathology in Fabry disease: evaluation of endomyocardial biopsies before and after enzyme replacement therapy. Circulation. 2009;119:2561-7 pubmed publisher
    ..This histopathological study should be a useful guide for clinicians and pathologists who diagnose and follow Fabry patients. ..
  36. Alroy J, Sabnis S, Kopp J. Renal pathology in Fabry disease. J Am Soc Nephrol. 2002;13 Suppl 2:S134-8 pubmed
  37. Najafian B, Svarstad E, Bostad L, Gubler M, Tøndel C, Whitley C, et al. Progressive podocyte injury and globotriaosylceramide (GL-3) accumulation in young patients with Fabry disease. Kidney Int. 2011;79:663-670 pubmed publisher
    ..Hence, podocyte injury may play a pivotal role in the development and progression of Fabry nephropathy. ..
  38. Khan F, Proulx F, Lingwood C. Detergent-resistant globotriaosyl ceramide may define verotoxin/glomeruli-restricted hemolytic uremic syndrome pathology. Kidney Int. 2009;75:1209-1216 pubmed publisher
    ..Our study shows that differential membrane Gb(3) organization in glomeruli and tubules provides a basis for the age- and glomerular-restricted pathology of hemolytic uremic syndrome. ..
  39. Pina D, Johannes L, Castanho M. Shiga toxin B-subunit sequential binding to its natural receptor in lipid membranes. Biochim Biophys Acta. 2007;1768:628-36 pubmed
    ..Based on our observations, a model of the protein-membrane interaction is proposed and the STxB membrane partition and binding constants were calculated. ..
  40. Roddy T, Nelson B, Sung C, Araghi S, Wilkens D, Zhang X, et al. Liquid chromatography-tandem mass spectrometry quantification of globotriaosylceramide in plasma for long-term monitoring of Fabry patients treated with enzyme replacement therapy. Clin Chem. 2005;51:237-40 pubmed
  41. Park J, Murray G, Limaye A, Quirk J, Gelderman M, Brady R, et al. Long-term correction of globotriaosylceramide storage in Fabry mice by recombinant adeno-associated virus-mediated gene transfer. Proc Natl Acad Sci U S A. 2003;100:3450-4 pubmed
    ..This study provides a basis for a simple and efficient gene-therapy approach for patients with Fabry disease and is indicative of its potential for the treatment of other lysosomal storage disorders. ..
  42. Bénichou B, Goyal S, Sung C, Norfleet A, O Brien F. A retrospective analysis of the potential impact of IgG antibodies to agalsidase beta on efficacy during enzyme replacement therapy for Fabry disease. Mol Genet Metab. 2009;96:4-12 pubmed publisher
  43. Branton M, Schiffmann R, Kopp J. Natural history and treatment of renal involvement in Fabry disease. J Am Soc Nephrol. 2002;13 Suppl 2:S139-43 pubmed
  44. Gariepy J. The use of Shiga-like toxin 1 in cancer therapy. Crit Rev Oncol Hematol. 2001;39:99-106 pubmed
    ..Finally, the known structural features of SLT-1 allow one to contemplate altering its receptor specificity in an effort to target CD77(-) tumor cell populations. ..
  45. Togawa T, Tsukimura T, Kodama T, Tanaka T, Kawashima I, Saito S, et al. Fabry disease: biochemical, pathological and structural studies of the ?-galactosidase A with E66Q amino acid substitution. Mol Genet Metab. 2012;105:615-20 pubmed publisher
    ..These results strongly suggest that the c.196G>C is not a pathogenic mutation but is a functional polymorphism...
  46. Khanna R, Soska R, Lun Y, Feng J, Frascella M, Young B, et al. The pharmacological chaperone 1-deoxygalactonojirimycin reduces tissue globotriaosylceramide levels in a mouse model of Fabry disease. Mol Ther. 2010;18:23-33 pubmed publisher
    ..Collectively, these data indicate that oral administration of DGJ increases mutant alpha-Gal A activity and reduces GL-3 in disease-relevant tissues in Tg/KO mice, and thus merits further evaluation as a treatment for Fabry disease. ..
  47. Eng C, Guffon N, Wilcox W, Germain D, Lee P, Waldek S, et al. Safety and efficacy of recombinant human alpha-galactosidase A replacement therapy in Fabry's disease. N Engl J Med. 2001;345:9-16 pubmed
  48. Schiffmann R, Kopp J, Austin H, Sabnis S, Moore D, Weibel T, et al. Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA. 2001;285:2743-9 pubmed
    ..Intravenous infusions of alpha-gal A are safe and have widespread therapeutic efficacy in Fabry disease. ..
  49. Benjamin E, Khanna R, Schilling A, Flanagan J, Pellegrino L, Brignol N, et al. Co-administration with the pharmacological chaperone AT1001 increases recombinant human ?-galactosidase A tissue uptake and improves substrate reduction in Fabry mice. Mol Ther. 2012;20:717-26 pubmed publisher
    ..Collectively, these data highlight the potentially beneficial effects of AT1001 on rh?-Gal A, thus warranting clinical investigation. ..
  50. Durant B, Forni S, Sweetman L, Brignol N, Meng X, Benjamin E, et al. Sex differences of urinary and kidney globotriaosylceramide and lyso-globotriaosylceramide in Fabry mice. J Lipid Res. 2011;52:1742-6 pubmed publisher
  51. Kolling G, Obata F, Gross L, Obrig T. Immunohistologic techniques for detecting the glycolipid Gb(3) in the mouse kidney and nervous system. Histochem Cell Biol. 2008;130:157-64 pubmed publisher
    ..These methods may serve as a basis for determining the localization of other amphipathic glycolipids in tissue. ..
  52. Hoey D, Sharp L, Currie C, Lingwood C, Gally D, Smith D. Verotoxin 1 binding to intestinal crypt epithelial cells results in localization to lysosomes and abrogation of toxicity. Cell Microbiol. 2003;5:85-97 pubmed
    ..These studies demonstrate that intestinal epithelium is an important determinant in VT interaction with major implications for the differential consequences of EHEC infection in reservoir hosts and humans. ..
  53. El Alaoui A, Schmidt F, Amessou M, Sarr M, Decaudin D, Florent J, et al. Shiga toxin-mediated retrograde delivery of a topoisomerase I inhibitor prodrug. Angew Chem Int Ed Engl. 2007;46:6469-72 pubmed
  54. Shu L, Shayman J. Caveolin-associated accumulation of globotriaosylceramide in the vascular endothelium of alpha-galactosidase A null mice. J Biol Chem. 2007;282:20960-7 pubmed
  55. Mignani R, Panichi V, Giudicissi A, Taccola D, Boscaro F, Feletti C, et al. Enzyme replacement therapy with agalsidase beta in kidney transplant patients with Fabry disease: a pilot study. Kidney Int. 2004;65:1381-5 pubmed
    ..Studies with longer courses of this and higher doses of ERT are merited in this population. ..
  56. Kitagawa T, Ishige N, Suzuki K, Owada M, Ohashi T, Kobayashi M, et al. Non-invasive screening method for Fabry disease by measuring globotriaosylceramide in whole urine samples using tandem mass spectrometry. Mol Genet Metab. 2005;85:196-202 pubmed
    ..We propose that this procedure can be used as a reliable, non-invasive, simple method for general and high-risk population screening for hemizygotic patients with the classic type and probably renal variant of Fabry disease. ..
  57. Utsunomiya I, Ren J, Taguchi K, Ariga T, Tai T, Ihara Y, et al. Immunohistochemical detection of verotoxin receptors in nervous system. Brain Res Brain Res Protoc. 2001;8:99-103 pubmed
    ..We also used a very simple method to identify the presence of lipofuscin-like autofluorescence which complicates fluorescence microscopy observation of aged human nervous tissues. ..
  58. Rutjes N, Binnington B, Smith C, Maloney M, Lingwood C. Differential tissue targeting and pathogenesis of verotoxins 1 and 2 in the mouse animal model. Kidney Int. 2002;62:832-45 pubmed
    ..The lung is a preferential (Gb(3)) "sink" for VT1, which explains the relatively slower clearance of VT2 and subsequent increased VT2 renal targeting and VT2 mortality in this animal model. ..
  59. Thurberg B, Rennke H, Colvin R, Dikman S, Gordon R, Collins A, et al. Globotriaosylceramide accumulation in the Fabry kidney is cleared from multiple cell types after enzyme replacement therapy. Kidney Int. 2002;62:1933-46 pubmed
  60. Tétaud C, Falguières T, Carlier K, Lecluse Y, Garibal J, Coulaud D, et al. Two distinct Gb3/CD77 signaling pathways leading to apoptosis are triggered by anti-Gb3/CD77 mAb and verotoxin-1. J Biol Chem. 2003;278:45200-8 pubmed
    ..VT-1- and anti-Gb3/CD77 mAb-treated cells displayed very different features on electron microscopy. These results clearly indicate that the binding of different ligands to Gb3/CD77 triggers completely different apoptotic pathways. ..
  61. Whitfield P, Calvin J, Hogg S, O Driscoll E, Halsall D, Burling K, et al. Monitoring enzyme replacement therapy in Fabry disease--role of urine globotriaosylceramide. J Inherit Metab Dis. 2005;28:21-33 pubmed
  62. Mattocks M, Bagovich M, De Rosa M, Bond S, Binnington B, Rasaiah V, et al. Treatment of neutral glycosphingolipid lysosomal storage diseases via inhibition of the ABC drug transporter, MDR1. Cyclosporin A can lower serum and liver globotriaosyl ceramide levels in the Fabry mouse model. FEBS J. 2006;273:2064-75 pubmed
    ..Hepatic venule endothelial and Kupffer cell VT1 staining was considerably reduced by in vivo CsA treatment. We conclude that MDR1 inhibition warrants consideration as a novel adjunct treatment for neutral GSL storage diseases. ..
  63. Xia C, Zhou D, Liu C, Lou Y, Yao Q, Zhang W, et al. Thio-isoglobotrihexosylceramide, an agonist for activating invariant natural killer T cells. Org Lett. 2006;8:5493-6 pubmed
    ..The biological assay showed that S-iGb3 demonstrates a much higher increase as a stimulatory ligand toward invariant natural killer T (iNKT) cells as compared to iGb3. [structure: see text]. ..
  64. Rodrigues L, Ferraz M, Rodrigues D, Pais Vieira M, Lima D, Brady R, et al. Neurophysiological, behavioral and morphological abnormalities in the Fabry knockout mice. Neurobiol Dis. 2009;33:48-56 pubmed publisher
    ..Our findings demonstrate for the first time that Fabry knockout mice have Gb3 accumulation in the peripheral nervous system, alterations in sensorimotor function, hypoalgesia and no impairment of motor nerve conduction. ..
  65. Kiguchi K, Iwamori Y, Suzuki N, Kobayashi Y, Ishizuka B, Ishiwata I, et al. Characteristic expression of globotriaosyl ceramide in human ovarian carcinoma-derived cells with anticancer drug resistance. Cancer Sci. 2006;97:1321-6 pubmed
  66. Vedder A, Linthorst G, van Breemen M, Groener J, Bemelman F, Strijland A, et al. The Dutch Fabry cohort: diversity of clinical manifestations and Gb3 levels. J Inherit Metab Dis. 2007;30:68-78 pubmed
  67. Yam G, Zuber C, Roth J. A synthetic chaperone corrects the trafficking defect and disease phenotype in a protein misfolding disorder. FASEB J. 2005;19:12-8 pubmed
    ..Small molecule chemical chaperones will be therapeutically useful for various lysosomal storage disorders as well as for other genetic metabolic disorders caused by mutant but nonetheless catalytically active enzymes. ..
  68. Wilcox W, Banikazemi M, Guffon N, Waldek S, Lee P, Linthorst G, et al. Long-term safety and efficacy of enzyme replacement therapy for Fabry disease. Am J Hum Genet. 2004;75:65-74 pubmed
    ..Thus, enzyme replacement therapy for 30-36 mo with agalsidase beta resulted in continuously decreased plasma GL-3 levels, sustained endothelial GL-3 clearance, stable kidney function, and a favorable safety profile. ..
  69. Muthing J, Schweppe C, Karch H, Friedrich A. Shiga toxins, glycosphingolipid diversity, and endothelial cell injury. Thromb Haemost. 2009;101:252-64 pubmed
    ..This approach may be helpful to gain insights into Stx-induced impairment of target cells that is suggested to originate at least partly from the structural heterogeneity of the cellular ligands of Stxs. ..
  70. Ogawa K, Hirai Y, Ishizaki M, Takahashi H, Hanawa H, Fukunaga Y, et al. Long-term inhibition of glycosphingolipid accumulation in Fabry model mice by a single systemic injection of AAV1 vector in the neonatal period. Mol Genet Metab. 2009;96:91-6 pubmed publisher
    ..Neonatal injection is effective to inhibit Gb3 accumulation and therefore, might help prevent failure of major organs during adulthood. ..
  71. Barisoni L, Jennette J, Colvin R, Sitaraman S, Bragat A, Castelli J, et al. Novel quantitative method to evaluate globotriaosylceramide inclusions in renal peritubular capillaries by virtual microscopy in patients with fabry disease. Arch Pathol Lab Med. 2012;136:816-24 pubmed publisher
    ..The virtual microscopy-based methodology increases accuracy and reproducibility; moreover, it provides a permanent record of retrievable data with full transparency in clinical trials. ..
  72. Prabakaran T, Nielsen R, Larsen J, Sørensen S, Feldt Rasmussen U, Saleem M, et al. Receptor-mediated endocytosis of ?-galactosidase A in human podocytes in Fabry disease. PLoS ONE. 2011;6:e25065 pubmed publisher
  73. Askari H, Kaneski C, Semino Mora C, Desai P, Ang A, Kleiner D, et al. Cellular and tissue localization of globotriaosylceramide in Fabry disease. Virchows Arch. 2007;451:823-34 pubmed
    ..These findings are crucial for the understanding of the disease mechanism and suggest the usefulness of immunostaining for globotriaosylceramide as a means to assess response to novel, specific therapies. ..
  74. Eisenhauer P, Chaturvedi P, Fine R, Ritchie A, Pober J, Cleary T, et al. Tumor necrosis factor alpha increases human cerebral endothelial cell Gb3 and sensitivity to Shiga toxin. Infect Immun. 2001;69:1889-94 pubmed
    ..Differential expression of Gb3 species may be a critical determinant of Shiga toxin toxicity and of CNS involvement in HUS. ..