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Ugcg  -  UDP-glucose ceramide glucosyltransferase

Mus musculus

Synonyms: AU043821, C80537, Ceramide glucosyltransferase, Epcs21, GCS, ...
 
 
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Disease relevance of Ugcg

 

High impact information on Ugcg

  • Transfection of ceramide glucosyltransferase or addition of glucosylsphingosine restored tyrosinase transport and pigmentation [4].
  • To gain insight into the role of GSLs in brain development and function, a cell-specific disruption of Ugcg was performed as indicated by the absence of virtually all glucosylceramide-based GSLs [5].
  • Thus, the presence of 11beta-HSD1 provides an additional means to facilitate GCS influences over lymphocyte activities, uncoupled from the plasma concentration of GCS [6].
  • The 11beta-hydroxysteroid dehydrogenase (11beta-HSD) enzymes control the interconversion of active glucocorticoids (GCS) and their inactive 11-keto metabolites, a process commonly referred to as the cortisone/cortisol shuttle [6].
  • Although the prereceptor metabolism of GCS by 11beta-HSD is well documented in a variety of cells and tissues, it has not yet been carefully investigated in the major cell types of the immune system [6].
 

Biological context of Ugcg

 

Anatomical context of Ugcg

  • The mice deficient in Ugcg expression in the nervous system show a striking loss of Purkinje cells and abnormal neurologic behavior [10].
  • We found that D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), a glucosylceramide synthase inhibitor, completely inhibits the osteoclast formation induced by macrophage-colony-stimulating factor and receptor activator of nuclear factor-kappa B ligand (RANKL) in a dose-dependent manner [11].
  • In vivo, this effect on T cell production of growth factors is manifest at low GCS concentrations that are well within physiologic ranges [12].
  • A specific inhibitor of glucosylceramide synthase, d-threo-1-phenyl-2-palmitoyl-3-pyrrolidino-propanol, was used to test the hypothesis that glycosphingolipids are required for the sorting of proteins to caveolae [13].
  • We have designed four siRNAs for the human GCS gene and transfected them into HeLa cells [14].
 

Associations of Ugcg with chemical compounds

 

Other interactions of Ugcg

  • When cre recombinase was expressed in the nervous system under control of the nestin promoter, the floxed gene underwent recombination, resulting in a substantial reduction of Ugcg expression and of glycosphingolipid ganglio-series levels [10].
  • Cell cycle arrest induced by an inhibitor of glucosylceramide synthase. Correlation with cyclin-dependent kinases [19].
  • Further, when glycosphingolipid expression was reduced approximately 40% with the glucosylceramide synthase inhibitor, d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, the percentage of trajectories exhibiting confinement and the size of the confining domain for Thy-1 were reduced approximately 1.5-fold [20].
  • Glucosylceramide synthase inhibitors (d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol [d-PDMP] and its analog) depleted gangliosides and this resulted in delayed expression of Disabled-2 (Dab-2), suggesting the involvement of gangliosides in F9 cell differentiation [21].
  • However, the Src kinases were eliminated from DIMs after depletion of the major neutral GSLs of J5 cells, glucosylceramide and lactosylceramide, by an inhibitor of glucosylceramide synthase (D-PDMP), indicating that GSLs in general are required for Src kinase association to DIM [22].
 

Analytical, diagnostic and therapeutic context of Ugcg

References

  1. Influence of cellular ganglioside depletion on tumor formation. Deng, W., Li, R., Ladisch, S. J. Natl. Cancer Inst. (2000) [Pubmed]
  2. Reduction of globotriaosylceramide in Fabry disease mice by substrate deprivation. Abe, A., Gregory, S., Lee, L., Killen, P.D., Brady, R.O., Kulkarni, A., Shayman, J.A. J. Clin. Invest. (2000) [Pubmed]
  3. Inhibition of experimental metastasis of murine Lewis lung carcinoma by an inhibitor of glucosylceramide synthase and its possible mechanism of action. Inokuchi, J., Jimbo, M., Momosaki, K., Shimeno, H., Nagamatsu, A., Radin, N.S. Cancer Res. (1990) [Pubmed]
  4. Glycosphingolipids are required for sorting melanosomal proteins in the Golgi complex. Sprong, H., Degroote, S., Claessens, T., van Drunen, J., Oorschot, V., Westerink, B.H., Hirabayashi, Y., Klumperman, J., van der Sluijs, P., van Meer, G. J. Cell Biol. (2001) [Pubmed]
  5. Cell-specific deletion of glucosylceramide synthase in brain leads to severe neural defects after birth. Jennemann, R., Sandhoff, R., Wang, S., Kiss, E., Gretz, N., Zuliani, C., Martin-Villalba, A., Jäger, R., Schorle, H., Kenzelmann, M., Bonrouhi, M., Wiegandt, H., Gröne, H.J. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  6. The expression of 11 beta-hydroxysteroid dehydrogenase type I by lymphocytes provides a novel means for intracrine regulation of glucocorticoid activities. Zhang, T.Y., Ding, X., Daynes, R.A. J. Immunol. (2005) [Pubmed]
  7. Assignment1 of a UDP-glucose:ceramide glucosyltransferase gene (Ugcg) to mouse chromosome band 4B3 by in situ hybridization. Ichikawa, S., Ozawa, K., Hirabayashi, Y. Cytogenet. Cell Genet. (1998) [Pubmed]
  8. Early developmental expression of the gene encoding glucosylceramide synthase, the enzyme controlling the first committed step of glycosphingolipid synthesis. Yamashita, T., Wada, R., Proia, R.L. Biochim. Biophys. Acta (2002) [Pubmed]
  9. Molecular cloning and expression of mouse ceramide glucosyltransferase. Ichikawa, S., Ozawa, K., Hirabayashi, Y. Biochem. Mol. Biol. Int. (1998) [Pubmed]
  10. Conditional LoxP-flanked glucosylceramide synthase allele controlling glycosphingolipid synthesis. Yamashita, T., Allende, M.L., Kalkofen, D.N., Werth, N., Sandhoff, K., Proia, R.L. Genesis (2005) [Pubmed]
  11. Lactosylceramide is essential for the osteoclastogenesis mediated by macrophage-colony-stimulating factor and receptor activator of nuclear factor-kappa B ligand. Iwamoto, T., Fukumoto, S., Kanaoka, K., Sakai, E., Shibata, M., Fukumoto, E., Inokuchi Ji, J., Takamiya, K., Furukawa, K., Furukawa, K., Kato, Y., Mizuno, A. J. Biol. Chem. (2001) [Pubmed]
  12. Contrasting effects of glucocorticoids on the capacity of T cells to produce the growth factors interleukin 2 and interleukin 4. Daynes, R.A., Araneo, B.A. Eur. J. Immunol. (1989) [Pubmed]
  13. Caveolar structure and protein sorting are maintained in NIH 3T3 cells independent of glycosphingolipid depletion. Shu, L., Lee, L., Chang, Y., Holzman, L.B., Edwards, C.A., Shelden, E., Shayman, J.A. Arch. Biochem. Biophys. (2000) [Pubmed]
  14. RNAi-mediated inhibition of the glucosylceramide synthase (GCS) gene: A preliminary study towards a therapeutic strategy for Gaucher disease and other glycosphingolipid storage diseases. Diaz-Font, A., Chab??s, A., Grinberg, D., Vilageliu, L. Blood Cells Mol. Dis. (2006) [Pubmed]
  15. Molecular cloning and characterization of the mouse ceramide glucosyltransferase gene. Ichikawa, S., Ozawa, K., Hirabayashi, Y. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  16. Glycolipids as immune modulatory tools. Lalazar, G., Preston, S., Zigmond, E., Y??acov, A.B., Ilan, Y. Mini reviews in medicinal chemistry (2006) [Pubmed]
  17. Regulation of intracellular ceramide content in B16 melanoma cells. Biological implications of ceramide glycosylation. Komori, H., Ichikawa, S., Hirabayashi, Y., Ito, M. J. Biol. Chem. (1999) [Pubmed]
  18. Ceramide mediates tumor-induced dendritic cell apoptosis. Kanto, T., Kalinski, P., Hunter, O.C., Lotze, M.T., Amoscato, A.A. J. Immunol. (2001) [Pubmed]
  19. Cell cycle arrest induced by an inhibitor of glucosylceramide synthase. Correlation with cyclin-dependent kinases. Rani, C.S., Abe, A., Chang, Y., Rosenzweig, N., Saltiel, A.R., Radin, N.S., Shayman, J.A. J. Biol. Chem. (1995) [Pubmed]
  20. Transient confinement of a glycosylphosphatidylinositol-anchored protein in the plasma membrane. Sheets, E.D., Lee, G.M., Simson, R., Jacobson, K. Biochemistry (1997) [Pubmed]
  21. Role for up-regulated ganglioside biosynthesis and association of Src family kinases with microdomains in retinoic acid-induced differentiation of F9 embryonal carcinoma cells. Sato, T., Zakaria, A.M., Uemura, S., Ishii, A., Ohno-Iwashita, Y., Igarashi, Y., Inokuchi, J. Glycobiology (2005) [Pubmed]
  22. Glycosphingolipid deficiency affects functional microdomain formation in Lewis lung carcinoma cells. Inokuchi, J.I., Uemura, S., Kabayama, K., Igarashi, Y. Glycoconj. J. (2000) [Pubmed]
  23. Up-regulation of neutral glycosphingolipid synthesis upon long term inhibition of ceramide synthesis by fumonisin B1. Meivar-Levy, I., Futerman, A.H. J. Biol. Chem. (1999) [Pubmed]
  24. Regulation of UDP-glucose:ceramide glucosyltransferase-1 by ceramide. Komori, H., Ichikawa, S., Hirabayashi, Y., Ito, M. FEBS Lett. (2000) [Pubmed]
  25. Agents for the treatment of glycosphingolipid storage disorders. Abe, A., Wild, S.R., Lee, W.L., Shayman, J.A. Curr. Drug Metab. (2001) [Pubmed]
 
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