Genomes and Genes
Summary: Cerebrosides which contain as their polar head group a glucose moiety bound in glycosidic linkage to the hydroxyl group of ceramides. Their accumulation in tissue, due to a defect in beta-glucosidase, is the cause of Gaucher's disease.
- Leipelt M, Warnecke D, Z hringer U, Ott C, M ller F, Hube B, et al. Glucosylceramide synthases, a gene family responsible for the biosynthesis of glucosphingolipids in animals, plants, and fungi. J Biol Chem. 2001;276:33621-9 pubmed publisherb>Glucosylceramides are membrane lipids in most eukaryotic organisms and in a few bacteria...
- Sun Y, Quinn B, Witte D, Grabowski G. Gaucher disease mouse models: point mutations at the acid beta-glucosidase locus combined with low-level prosaposin expression lead to disease variants. J Lipid Res. 2005;46:2102-13 pubmed..These models mimic a more severe Gaucher disease phenotype and could be useful for therapeutic intervention studies. ..
- Boot R, Verhoek M, Donker Koopman W, Strijland A, van Marle J, Overkleeft H, et al. Identification of the non-lysosomal glucosylceramidase as beta-glucosidase 2. J Biol Chem. 2007;282:1305-12 pubmed..Allegood, J. C., Warren, R. L., Ramirez, D. M., Hammer, R. E., Hamra, F. K., Matern, S., and Russell, D. W. (2006) J. Clin. Invest. 116, 2985-2994). In conclusion, GBA2 plays a role in cellular glucosylceramide metabolism. ..
- Campeau P, Rafei M, Boivin M, Sun Y, Grabowski G, Galipeau J. Characterization of Gaucher disease bone marrow mesenchymal stromal cells reveals an altered inflammatory secretome. Blood. 2009;114:3181-90 pubmed publisher..In conclusion, Gaucher disease MSCs display an altered secretome that could contribute to skeletal disease and immune disease manifestations in a manner distinct and additive to Gaucher macrophages themselves. ..
- Fujiwara K, Kitatani K, Fukushima K, Yazama H, Umehara H, Kikuchi M, et al. Inhibitory effects of dietary glucosylceramides on squamous cell carcinoma of the head and neck in NOD/SCID mice. Int J Clin Oncol. 2011;16:133-40 pubmed publisher..We investigated the effects of dietary glucosylceramides, sphingolipids isolated from rice bran, on tumor growth of human head and neck squamous cell carcinoma...
- Groener J, Poorthuis B, Kuiper S, Helmond M, Hollak C, Aerts J. HPLC for simultaneous quantification of total ceramide, glucosylceramide, and ceramide trihexoside concentrations in plasma. Clin Chem. 2007;53:742-7 pubmed..HPLC enables quantification of total Cer, GlcCer, and CTH in plasma and is useful for the follow-up of patients on therapy for Gaucher or Fabry disease. ..
- Sun Y, Liou B, Ran H, Skelton M, Williams M, Vorhees C, et al. Neuronopathic Gaucher disease in the mouse: viable combined selective saposin C deficiency and mutant glucocerebrosidase (V394L) mice with glucosylsphingosine and glucosylceramide accumulation and progressive neurological deficits. Hum Mol Genet. 2010;19:1088-97 pubmed publisher
- Hamanaka S, Hara M, Nishio H, Otsuka F, Suzuki A, Uchida Y. Human epidermal glucosylceramides are major precursors of stratum corneum ceramides. J Invest Dermatol. 2002;119:416-23 pubmed..studies indicated that beta-glucocerebrosidase- and sphingomyelinase-dependent ceramide production from glucosylceramides and sphingomyelins, respectively, is important for epidermal permeability barrier homeostasis...
- Díaz de Vivar M, Seldes A, Maier M. Two novel glucosylceramides from gonads and body walls of the Patagonian starfish Allostichaster inaequalis. Lipids. 2002;37:597-603 pubmed..extract of the gonads and body walls of the Patagonian starfish Allostichaster inaequalis, two new glucosylceramides (4 and 7) were isolated together with the known phalluside-1 (1) and two glucosylceramides (2 and 3) ..
- Pinto M, Rodrigues M, Travassos L, Haido R, Wait R, Barreto Bergter E. Characterization of glucosylceramides in Pseudallescheria boydii and their involvement in fungal differentiation. Glycobiology. 2002;12:251-60 pubmed..boydii synthesizes glucosylceramides as major neutral glycosphingolipids. CMHs from P...
- Sugawara T, Aida K, Duan J, Hirata T. Analysis of glucosylceramides from various sources by liquid chromatography-ion trap mass spectrometry. J Oleo Sci. 2010;59:387-94 pubmed..In this study, we attempted to identify the chemical structures of glucosylceramides from maize, rice, mushroom (maitake) and sea cucumber by liquid chromatography-ion trap mass spectrometry...
- Fuller M, Rozaklis T, Lovejoy M, Zarrinkalam K, Hopwood J, Meikle P. Glucosylceramide accumulation is not confined to the lysosome in fibroblasts from patients with Gaucher disease. Mol Genet Metab. 2008;93:437-43 pubmed..The accumulation of lipids in the endosome and lysosome suggests both impaired trafficking of lipids and reduced capacity of the lysosome to degrade lipids. ..
- Kechichian T, Shea J, Del Poeta M. Depletion of alveolar macrophages decreases the dissemination of a glucosylceramide-deficient mutant of Cryptococcus neoformans in immunodeficient mice. Infect Immun. 2007;75:4792-8 pubmed..This study highlights the hypothesis that AMs may exacerbate C. neoformans infection in conditions in which there is severe host immunodeficiency. ..
- Hein L, Meikle P, Hopwood J, Fuller M. Secondary sphingolipid accumulation in a macrophage model of Gaucher disease. Mol Genet Metab. 2007;92:336-45 pubmed
- Ramamoorthy V, Cahoon E, Li J, Thokala M, Minto R, Shah D. Glucosylceramide synthase is essential for alfalfa defensin-mediated growth inhibition but not for pathogenicity of Fusarium graminearum. Mol Microbiol. 2007;66:771-86 pubmed..Based on our findings, we conclude that glucosylceramide is essential for MsDef1-mediated growth inhibition of F. graminearum, but its role in fungal pathogenesis is host-dependent. ..
- Saito M, Saito M, Cooper T, Vadasz C. Ethanol-induced changes in the content of triglycerides, ceramides, and glucosylceramides in cultured neurons. Alcohol Clin Exp Res. 2005;29:1374-83 pubmed..Further, ethanol-induced changes in lipid metabolism, specifically those of ceramide and GlcCer, may be related to the ethanol-induced apoptotic pathway. ..
- Ahn Y, Lee W, Jung J, Lee S, Hong J. Structural determination of glucosylceramides isolated from marine sponge by fast atom bombardment collision-induced dissociation linked scan at constant B/E. J Mass Spectrom. 2009;44:1698-708 pubmed publisherFive glucosylceramides (GlcCers) were isolated by reversed phase high-performance liquid chromatography from the MeOH extracts of a marine sponge, Haliclona (Reniera) sp...
- Pelled D, Trajkovic Bodennec S, Lloyd Evans E, Sidransky E, Schiffmann R, Futerman A. Enhanced calcium release in the acute neuronopathic form of Gaucher disease. Neurobiol Dis. 2005;18:83-8 pubmed..These findings suggest that defective calcium homeostasis may be a mechanism responsible for neuropathophysiology in acute neuronopathic Gaucher disease, and may potentially offer new therapeutic approaches for disease management. ..
- Doering T, Proia R, Sandhoff K. Accumulation of protein-bound epidermal glucosylceramides in beta-glucocerebrosidase deficient type 2 Gaucher mice. FEBS Lett. 1999;447:167-70 pubmed..Ceramides, the main components of these membranes, derive in large part from hydrolysis of glucosylceramides mediated by the lysosomal enzyme beta-glucocerebrosidase...
- Gornati R, Berra B, Montorfano G, Martini C, Ciana G, Ferrari P, et al. Glycolipid analysis of different tissues and cerebrospinal fluid in type II Gaucher disease. J Inherit Metab Dis. 2002;25:47-55 pubmed..These data could be useful in the effort to clarify the pathophysiological mechanism of brain damage in neuronopathic Gaucher disease. ..
- Levery S, Momany M, Lindsey R, Toledo M, Shayman J, Fuller M, et al. Disruption of the glucosylceramide biosynthetic pathway in Aspergillus nidulans and Aspergillus fumigatus by inhibitors of UDP-Glc:ceramide glucosyltransferase strongly affects spore germination, cell cycle, and hyphal growth. FEBS Lett. 2002;525:59-64 pubmed..fumigatus cultured in the presence of these inhibitors displayed a significantly reduced GlcCer/GalCer ratio. These results suggest that synthesis of GlcCer is essential for normal development of A. fumigatus and A. nidulans. ..
- Ilan Y, Elstein D, Zimran A. Glucocerebroside: an evolutionary advantage for patients with Gaucher disease and a new immunomodulatory agent. Immunol Cell Biol. 2009;87:514-24 pubmed publisher..Indirectly, these data support treating symptomatic patients with mild/moderate GD with low-dose ERT and re-evaluating the use of ERT in asymptomatic patients. ..
- Takakuwa N, Ohnishi M, Oda Y. Significance of the KlLAC1 gene in glucosylceramide production by Kluyveromyces lactis. FEMS Yeast Res. 2008;8:839-45 pubmed publisher..The LAC1 protein of K. lactis is the enzyme that plays a crucial role in the synthesis of glucosylceramide. ..
- da Silva A, Rodrigues M, Farias S, Almeida I, Pinto M, Barreto Bergter E. Glucosylceramides in Colletotrichum gloeosporioides are involved in the differentiation of conidia into mycelial cells. FEBS Lett. 2004;561:137-43 pubmedb>Glucosylceramides (GlcCer) were extracted from the plant pathogen Colletotrichum gloeosporioides and purified by several chromatographic steps...
- Hein L, Duplock S, Hopwood J, Fuller M. Lipid composition of microdomains is altered in a cell model of Gaucher disease. J Lipid Res. 2008;49:1725-34 pubmed publisher..Analysis of individual lipid species revealed preservation of the shorter and fully saturated fatty acid species in the DRM, suggesting that the highly ordered and tightly packed nature of the DRM is maintained. ..
- Rodrigues M, Nimrichter L, Oliveira D, Frases S, Miranda K, Zaragoza O, et al. Vesicular polysaccharide export in Cryptococcus neoformans is a eukaryotic solution to the problem of fungal trans-cell wall transport. Eukaryot Cell. 2007;6:48-59 pubmed..The results imply a novel mechanism for the release of the major virulence factor of C. neoformans whereby polysaccharide packaged in lipid vesicles crosses the cell wall and the capsule network to reach the extracellular environment. ..
- Tuuf J, Mattjus P. Human glycolipid transfer protein--intracellular localization and effects on the sphingolipid synthesis. Biochim Biophys Acta. 2007;1771:1353-63 pubmed..We propose that GLTP is not likely involved in the de novo synthesis of glycosphingolipids, but could rather have a role as a glycolipid sensor for the cellular levels of glucosylceramide. ..
- Warnecke D, Heinz E. Recently discovered functions of glucosylceramides in plants and fungi. Cell Mol Life Sci. 2003;60:919-41 pubmed..However, there are specific differences in the structure of the ceramide backbone of glucosylceramides from these organisms...
- Sun Y, Liou B, Xu Y, Quinn B, Zhang W, Hamler R, et al. Ex vivo and in vivo effects of isofagomine on acid ?-glucosidase variants and substrate levels in Gaucher disease. J Biol Chem. 2012;287:4275-87 pubmed publisher..Decreases of storage cells were correlated with >50% reductions in substrate levels. These results indicate that IFG stabilizes GCase in tissues and serum and can reduce visceral substrates in vivo...
- Kok J, Babia T, Filipeanu C, Nelemans A, Egea G, Hoekstra D. PDMP blocks brefeldin A-induced retrograde membrane transport from golgi to ER: evidence for involvement of calcium homeostasis and dissociation from sphingolipid metabolism. J Cell Biol. 1998;142:25-38 pubmed..Thus, the biological effects of PDMP revealed a relation between three important physiological processes of multidrug resistance, calcium homeostasis, and membrane flow in the ER/ Golgi system. ..
- Rhome R, McQuiston T, Kechichian T, Bielawska A, Hennig M, Drago M, et al. Biosynthesis and immunogenicity of glucosylceramide in Cryptococcus neoformans and other human pathogens. Eukaryot Cell. 2007;6:1715-26 pubmed
- Jmoudiak M, Futerman A. Gaucher disease: pathological mechanisms and modern management. Br J Haematol. 2005;129:178-88 pubmed..This review, after discussing pathological mechanisms, evaluates the advantages and disadvantages of existing therapies. ..
- Sun Y, Witte D, Zamzow M, Ran H, Quinn B, Matsuda J, et al. Combined saposin C and D deficiencies in mice lead to a neuronopathic phenotype, glucosylceramide and alpha-hydroxy ceramide accumulation, and altered prosaposin trafficking. Hum Mol Genet. 2007;16:957-71 pubmed..Marked accumulations of glucosylceramides and alpha-hydroxy ceramides were present in brain and kidney...
- Saito K, Takakuwa N, Ohnishi M, Oda Y. Presence of glucosylceramide in yeast and its relation to alkali tolerance of yeast. Appl Microbiol Biotechnol. 2006;71:515-21 pubmed..5 even though the parent strain could grow under the same conditions. These results indicate that glucosylceramide in yeast might be a component that enables yeast to grow under alkali conditions. ..
- Hillig I, Leipelt M, Ott C, Zahringer U, Warnecke D, Heinz E. Formation of glucosylceramide and sterol glucoside by a UDP-glucose-dependent glucosylceramide synthase from cotton expressed in Pichia pastoris. FEBS Lett. 2003;553:365-9 pubmed
- Thevissen K, Warnecke D, Francois I, Leipelt M, Heinz E, Ott C, et al. Defensins from insects and plants interact with fungal glucosylceramides. J Biol Chem. 2004;279:3900-5 pubmed..In an enzyme-linked immunosorbent assay-based binding assay, RsAFP2 was found to interact with glucosylceramides isolated from P. pastoris but not with soybean nor human glucosylceramides. Furthermore, the P...
- Aerts J, Ottenhoff R, Powlson A, Grefhorst A, van Eijk M, Dubbelhuis P, et al. Pharmacological inhibition of glucosylceramide synthase enhances insulin sensitivity. Diabetes. 2007;56:1341-9 pubmed
- Maier M, Kuriss A, Seldes A. Isolation and structure of glucosylceramides from the starfish Cosmasterias lurida. Lipids. 1998;33:825-7 pubmed..lipid fraction of the methylene chloride/methanol extract of the starfish Cosmasterias lurida, two new glucosylceramides together with a known glucosylceramide, ophidiacerebroside E, were isolated by chromatographic procedures ..
- De Rosa M, Sillence D, Ackerley C, Lingwood C. Role of multiple drug resistance protein 1 in neutral but not acidic glycosphingolipid biosynthesis. J Biol Chem. 2004;279:7867-76 pubmed..These studies identify MDR1 as the major glucosyl ceramide flippase required for neutral glycosphingolipid anabolism and demonstrate a previously unappreciated dichotomy between neutral and acid glycosphingolipid synthesis. ..
- Xu Y, Reboulet R, Quinn B, Huelsken J, Witte D, Grabowski G. Dependence of reversibility and progression of mouse neuronopathic Gaucher disease on acid beta-glucosidase residual activity levels. Mol Genet Metab. 2008;94:190-203 pubmed publisher..The persistent CNS deterioration, histologic abnormalities, and glucosylceramide storage in the CBE-treated D409V mice revealed a threshold level of GCase activity necessary for the prevention of progression of CNS involvement. ..
- Nicholson K, Quinn D, Kellett G, Warr J. Preferential killing of multidrug-resistant KB cells by inhibitors of glucosylceramide synthase. Br J Cancer. 1999;81:423-30 pubmed..These results suggest that the manipulation of glucosylceramide levels may be a fruitful way of causing the preferential killing of MDR cells in vitro and possibly in vivo. ..
- Halter D, Neumann S, van Dijk S, Wolthoorn J, De Mazière A, Vieira O, et al. Pre- and post-Golgi translocation of glucosylceramide in glycosphingolipid synthesis. J Cell Biol. 2007;179:101-15 pubmed..FAPP2 knockdown strongly reduces GM3 synthesis. Overall, we show that newly synthesized GlcCer enters two pathways: one toward the noncytosolic surface of a post-Golgi membrane and one via the ER toward the Golgi lumen LacCer synthase. ..
- Marshall J, McEachern K, Kyros J, Nietupski J, Budzinski T, Ziegler R, et al. Demonstration of feasibility of in vivo gene therapy for Gaucher disease using a chemically induced mouse model. Mol Ther. 2002;6:179-89 pubmed..Together, these data demonstrate the potential for use of in vivo gene therapy vectors for treating Gaucher disease. ..
- Hayashi Y, Okino N, Kakuta Y, Shikanai T, Tani M, Narimatsu H, et al. Klotho-related protein is a novel cytosolic neutral beta-glycosylceramidase. J Biol Chem. 2007;282:30889-900 pubmed..GlcCer was found to fit well the cleft of the crystal structure of KLrP. Collectively, KLrP was identified as a cytosolic neutral glycosylceramidase that could be involved in a novel nonlysosomal catabolic pathway of GlcCer. ..
- Bodennec J, Pelled D, Riebeling C, Trajkovic S, Futerman A. Phosphatidylcholine synthesis is elevated in neuronal models of Gaucher disease due to direct activation of CTP:phosphocholine cytidylyltransferase by glucosylceramide. FASEB J. 2002;16:1814-6 pubmed..Together, these data demonstrate that GlcCer directly activates CCT, which results in elevated PC synthesis, which may account for some of the changes in growth rates observed upon neuronal GlcCer accumulation. ..
- Chavez J, Siddique M, Wang S, Ching J, Shayman J, Summers S. Ceramides and glucosylceramides are independent antagonists of insulin signaling. J Biol Chem. 2014;289:723-34 pubmed publisher..These data have important mechanistic implications for understanding how these sphingolipids contribute to energy sensing and the disruption of anabolism under conditions of nutrient oversupply. ..
- Takagi Y, Nakagawa H, Matsuo N, Nomura T, Takizawa M, Imokawa G. Biosynthesis of acylceramide in murine epidermis: characterization by inhibition of glucosylation and deglucosylation, and by substrate specificity. J Invest Dermatol. 2004;122:722-9 pubmed
- Oku H, Wongtangtintharn S, Iwasaki H, Inafuku M, Shimatani M, Toda T. Tumor specific cytotoxicity of glucosylceramide. Cancer Chemother Pharmacol. 2007;60:767-75 pubmed..The underlying mechanism for the selectivity remains to be answered in the forthcoming study. ..
- Chatterjee S, Alsaeedi N, Hou J, Bandaru V, Wu L, Halushka M, et al. Use of a glycolipid inhibitor to ameliorate renal cancer in a mouse model. PLoS ONE. 2013;8:e63726 pubmed publisher..Thus inhibiting glycosphingolipid synthesis can be a bonafide target to prevent the progression of other types of cancer. ..
- Ilan Y, Ohana M, Pappo O, Margalit M, Lalazar G, Engelhardt D, et al. Alleviation of acute and chronic graft-versus-host disease in a murine model is associated with glucocerebroside-enhanced natural killer T lymphocyte plasticity. Transplantation. 2007;83:458-67 pubmed..GC may alleviate immunologically incongruous disorders, and may be associated with "fine tuning" of immune responses. ..
- Sakai K, Akiyama M, Sugiyama Nakagiri Y, McMillan J, Sawamura D, Shimizu H. Localization of ABCA12 from Golgi apparatus to lamellar granules in human upper epidermal keratinocytes. Exp Dermatol. 2007;16:920-6 pubmed..These results indicate that ABCA12 plays an important role in lipid transport from the Golgi apparatus to LG in human granular layer keratinocytes...
- Mor V, Farnoud A, Singh A, Rella A, Tanno H, Ishii K, et al. Glucosylceramide Administration as a Vaccination Strategy in Mouse Models of Cryptococcosis. PLoS ONE. 2016;11:e0153853 pubmed publisher..Taken together, our results suggest that fungal GlcCer can protect mice against lethal doses of C. neoformans infection and can provide a viable vaccination strategy against Cryptococcus. ..
- Mizrahi M, Lalazar G, Ben Ya acov A, Livovsky D, Horowitz Y, Zolotarov L, et al. Beta-glycoglycosphingolipid-induced augmentation of the anti-HBV immune response is associated with altered CD8 and NKT lymphocyte distribution: a novel adjuvant for HBV vaccination. Vaccine. 2008;26:2589-95 pubmed publisher
- Fitzgerald R, Walters J. Accumulation of topical naproxen by cultured oral epithelium. J Dent Res. 2007;86:775-9 pubmed..The individual and combined effects of glycerol and Pluronic F-127 were of lesser magnitude than those obtained with glucosylceramide or at pH 6.3. Thus, SCC-25 cells possess transporters for naproxen. ..
- van Lummel M, van Blitterswijk W, Vink S, Veldman R, van der Valk M, Schipper D, et al. Enriching lipid nanovesicles with short-chain glucosylceramide improves doxorubicin delivery and efficacy in solid tumors. FASEB J. 2011;25:280-9 pubmed publisher..This new drug delivery concept, aiming at increased membrane permeability for amphiphilic drugs, provides an opportunity to improve cancer chemotherapy. ..
- Kisa F, Yamada K, Kaneko M, Inagaki M, Higuchi R. Constituents of holothuroidea, 14. Isolation and structure of new glucocerebroside molecular species from the sea cucumber Stichopus japonicus. Chem Pharm Bull (Tokyo). 2005;53:382-6 pubmed..SJC-4 and SJC-5 are also sphingosine-type glucocerebroside molecular species with hydroxylated fatty acyl moieties, although they are new glucocerebroside molecular species with unique sphingosine bases. ..
- Hartmann M, Perret A, Carde J, Cassagne C, Moreau P. Inhibition of the sterol pathway in leek seedlings impairs phosphatidylserine and glucosylceramide synthesis but triggers an accumulation of triacylglycerols. Biochim Biophys Acta. 2002;1583:285-96 pubmed..Taken together, the present data emphasize that a coordinated regulation of the biosynthetic pathways of sterols and some specific lipid molecular species could take place during plant membrane biogenesis. ..
- Kamada N, Iijima H, Kimura K, Harada M, Shimizu E, Motohashi Si -, et al. Crucial amino acid residues of mouse CD1d for glycolipid ligand presentation to V(alpha)14 NKT cells. Int Immunol. 2001;13:853-61 pubmed..The possibility that Glu83 is a contact site for the NKT cell receptor is also discussed. ..
- Mazzulli J, Xu Y, Sun Y, Knight A, McLean P, Caldwell G, et al. Gaucher disease glucocerebrosidase and Î±-synuclein form a bidirectional pathogenic loop in synucleinopathies. Cell. 2011;146:37-52 pubmed publisher..Therefore, improved targeting of GCase to lysosomes may represent a specific therapeutic approach for PD and other synucleinopathies. ..
- Yeom M, Kim S, Lee B, Han J, Chung G, Choi H, et al. Oral administration of glucosylceramide ameliorates inflammatory dry-skin condition in chronic oxazolone-induced irritant contact dermatitis in the mouse ear. J Dermatol Sci. 2012;67:101-10 pubmed publisher..A major characteristic of chronic ICD is an inflammatory dry-skin condition with associated itching. Although glucosylceramide (GlcCer) is known to improve the skin barrier function, its mechanism of action is unknown...