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UGCG  -  UDP-glucose ceramide glucosyltransferase

Homo sapiens

Synonyms: Ceramide glucosyltransferase, GCS, GLCT-1, GLCT1, Glucosylceramide synthase, ...
 
 
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Disease relevance of UGCG

 

Psychiatry related information on UGCG

 

High impact information on UGCG

 

Chemical compound and disease context of UGCG

 

Biological context of UGCG

 

Anatomical context of UGCG

  • We treated both multidrug-resistant cell lines with the glucosylceramide synthase inhibitors PDMP (d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol), C9DGJ (N-nonyl-deoxygalactonojirimycin) or C4DGJ (N-butyl-deoxygalactonojirimycin) [21].
  • Thus, GCS, located at the Golgi, is topologically segregated from Cer produced in the plasma membrane [23].
  • We now report that inhibition of glucosylceramide synthase using d,l-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) or 1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP) protected U937 and HL-60 cells from DNR-induced apoptosis [24].
  • Jurkat cells, retrovirally transduced with GCS cDNA, showed a 10-12-fold increase in GCS activity in vitro and a 7-fold elevated basal GlcCer level in vivo [23].
  • We report that IFG has little or no inhibitory activity towards intestinal disaccharidase enzymes, ER alpha-glucosidase II or glucosylceramide synthase at concentrations previously shown to enhance N370S GlcCerase folding and trafficking in Gaucher fibroblasts [25].
 

Associations of UGCG with chemical compounds

 

Physical interactions of UGCG

 

Regulatory relationships of UGCG

 

Other interactions of UGCG

 

Analytical, diagnostic and therapeutic context of UGCG

  • The main structural features of the UCCG and UGCG tetraloops are similar to those previously found in the UUCG and UACG tetraloops by means of NMR and vibrational spectroscopies, except those of the second nucleosides of the tetraloops (rC and rG, respectively) which adopt a 3'-endo/anti rather than a 2'-endo/anti conformation [34].
  • 8-kilobase transcript on Northern blots, and GCS protein, a approximately 38-kDa polypeptide detected by Western blotting, increased dramatically (approximately 5-fold) during differentiation, reaching a maximum at about day 8 [20].
  • However, Cer accumulating during apoptosis induced by ligation of the death receptor CD95, treatment with the anti-cancer drug etoposide, or exposure to gamma-radiation was not glycosylated by GCS [23].
  • The levels of alpha B-crystallin, as measured by Northern blot and immunoblot analyses, were increased by the addition of an exogenous short-chain ceramide, N-acetylsphingosine, or by increasing endogenous intracellular ceramide by inhibition of glucosylceramide synthase [35].
  • In that study, doxorubicin promoted generation of ceramide in MCF-7-AdrR/GCS antisense cells; the present study implicates factors in addition to ceramide that augment sensitivity to chemotherapy [15].

References

  1. Glucosylceramide synthase and its functional interaction with RTN-1C regulate chemotherapeutic-induced apoptosis in neuroepithelioma cells. Di Sano, F., Fazi, B., Citro, G., Lovat, P.E., Cesareni, G., Piacentini, M. Cancer Res. (2003) [Pubmed]
  2. Variant effects of non-native kissing-loop hairpin palindromes on HIV replication and HIV RNA dimerization: role of stem-loop B in HIV replication and HIV RNA dimerization. Laughrea, M., Shen, N., Jetté, L., Wainberg, M.A. Biochemistry (1999) [Pubmed]
  3. P-glycoprotein is implicated in the inhibition of ceramide-induced apoptosis in TF-1 acute myeloid leukemia cells by modulation of the glucosylceramide synthase pathway. Turzanski, J., Grundy, M., Shang, S., Russell, N., Pallis, M. Exp. Hematol. (2005) [Pubmed]
  4. Identification of a common mutation in Finnish patients with nonketotic hyperglycinemia. Kure, S., Takayanagi, M., Narisawa, K., Tada, K., Leisti, J. J. Clin. Invest. (1992) [Pubmed]
  5. Hypertrophic cardiomyopathy. Evaluation by gated cardiac blood pool scanning. Pohost, G.M., Vignola, P.A., McKusick, K.E., Block, P.C., Myers, G.S., Walker, H.J., Copen, D.L., Dinsmore, R.E. Circulation (1977) [Pubmed]
  6. Elevated serum S-100B protein as a predictor of failure to short-term return to work or activities after mild head injury. Stranjalis, G., Korfias, S., Papapetrou, C., Kouyialis, A., Boviatsis, E., Psachoulia, C., Sakas, D.E. J. Neurotrauma (2004) [Pubmed]
  7. Current status and perspectives in ceramide-targeting molecular medicine. Sawai, H., Domae, N., Okazaki, T. Curr. Pharm. Des. (2005) [Pubmed]
  8. The relationship between false confessions and perceptions of parental rearing practices. Gudjonsson, G.H., Sigurdsson, J.F., Finnbogadottir, H., Smari, U.J. Scandinavian journal of psychology. (2006) [Pubmed]
  9. Scene transport of pediatric patients injured at winter resorts. McCowan, C.L., Swanson, E.R., Thomas, F., Hartsell, S., Allen, T.L., Handrahan, D.L., Kwok, K. Prehospital emergency care : official journal of the National Association of EMS Physicians and the National Association of State EMS Directors. (2006) [Pubmed]
  10. Diagnostic confusion in mild traumatic brain injury (MTBI). Lessons from clinical practice and EFNS--inquiry. European Federation of Neurological Societies. von Wild, K., Terwey, S. Brain injury : [BI]. (2001) [Pubmed]
  11. Glucosylceramide synthase is an essential regulator of pathogenicity of Cryptococcus neoformans. Rittershaus, P.C., Kechichian, T.B., Allegood, J.C., Merrill, A.H., Hennig, M., Luberto, C., Del Poeta, M. J. Clin. Invest. (2006) [Pubmed]
  12. Expression cloning of a cDNA for human ceramide glucosyltransferase that catalyzes the first glycosylation step of glycosphingolipid synthesis. Ichikawa, S., Sakiyama, H., Suzuki, G., Hidari, K.I., Hirabayashi, Y. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  13. Expression cloning of a cDNA for human ceramide glucosyltransferase that catalyzes the first glycosylation step of glycosphingolipid synthesis. Ichikawa, S., Sakiyama, H., Suzuki, G., Hidari, K.I., Hirabayashi, Y. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  14. Interleukin-2-induced survival of natural killer (NK) cells involving phosphatidylinositol-3 kinase-dependent reduction of ceramide through acid sphingomyelinase, sphingomyelin synthase, and glucosylceramide synthase. Taguchi, Y., Kondo, T., Watanabe, M., Miyaji, M., Umehara, H., Kozutsumi, Y., Okazaki, T. Blood (2004) [Pubmed]
  15. Glucosylceramide synthase blockade down-regulates P-glycoprotein and resensitizes multidrug-resistant breast cancer cells to anticancer drugs. Gouazé, V., Liu, Y.Y., Prickett, C.S., Yu, J.Y., Giuliano, A.E., Cabot, M.C. Cancer Res. (2005) [Pubmed]
  16. Expression of glucosylceramide synthase, converting ceramide to glucosylceramide, confers adriamycin resistance in human breast cancer cells. Liu, Y.Y., Han, T.Y., Giuliano, A.E., Cabot, M.C. J. Biol. Chem. (1999) [Pubmed]
  17. Metabolic crisis without brain ischemia is common after traumatic brain injury: a combined microdialysis and positron emission tomography study. Vespa, P., Bergsneider, M., Hattori, N., Wu, H.M., Huang, S.C., Martin, N.A., Glenn, T.C., McArthur, D.L., Hovda, D.A. J. Cereb. Blood Flow Metab. (2005) [Pubmed]
  18. Miglustat. McCormack, P.L., Goa, K.L. Drugs (2003) [Pubmed]
  19. Assignment of a UDP-glucose:ceramide glucosyltransferase gene (UGCG) to human chromosome band 9q31 by in situ hybridization. Ichikawa, S., Ozawa, K., Hirabayashi, Y. Cytogenet. Cell Genet. (1997) [Pubmed]
  20. Up-regulation of glucosylceramide synthase expression and activity during human keratinocyte differentiation. Watanabe, R., Wu, K., Paul, P., Marks, D.L., Kobayashi, T., Pittelkow, M.R., Pagano, R.E. J. Biol. Chem. (1998) [Pubmed]
  21. Inhibition of glucosylceramide synthase does not reverse drug resistance in cancer cells. Norris-Cervetto, E., Callaghan, R., Platt, F.M., Dwek, R.A., Butters, T.D. J. Biol. Chem. (2004) [Pubmed]
  22. Ceramide glycosylation potentiates cellular multidrug resistance. Liu, Y.Y., Han, T.Y., Giuliano, A.E., Cabot, M.C. FASEB J. (2001) [Pubmed]
  23. Glucosylceramide synthase does not attenuate the ceramide pool accumulating during apoptosis induced by CD95 or anti-cancer regimens. Tepper, A.D., Diks, S.H., van Blitterswijk, W.J., Borst, J. J. Biol. Chem. (2000) [Pubmed]
  24. Cytoprotective effect of glucosylceramide synthase inhibition against daunorubicin-induced apoptosis in human leukemic cell lines. Grazide, S., Terrisse, A.D., Lerouge, S., Laurent, G., Jaffrézou, J.P. J. Biol. Chem. (2004) [Pubmed]
  25. Selective action of the iminosugar isofagomine, a pharmacological chaperone for mutant forms of acid-beta-glucosidase. Steet, R., Chung, S., Lee, W.S., Pine, C.W., Do, H., Kornfeld, S. Biochem. Pharmacol. (2007) [Pubmed]
  26. Ceramide reduction and transcriptional up-regulation of glucosylceramide synthase through doxorubicin-activated Sp1 in drug-resistant HL-60/ADR cells. Uchida, Y., Itoh, M., Taguchi, Y., Yamaoka, S., Umehara, H., Ichikawa, S., Hirabayashi, Y., Holleran, W.M., Okazaki, T. Cancer Res. (2004) [Pubmed]
  27. Can P-glycoprotein influence the bioavailability of iminosugar-based glucosylceramide synthase inhibitors? Norris-Cervetto, E., Butters, T.D., Martin, C., Modok, S., Dwek, R.A., Callaghan, R. Eur. J. Pharmacol. (2006) [Pubmed]
  28. Two glucosylceramide synthase inhibitors attenuate doxorubicin-induced p21Cip1/Waf1 upregulation in HepG2 cells, irrespective of their differential chemosensitizing properties. Di Bartolomeo, S., Spinedi, A. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  29. Development of a mammalian Tet-on expression cell line: glucosylceramide synthase regulates TNF-alpha-induced apoptosis. Liu, Y.Y., Cabot, M.C. Methods Mol. Biol. (2004) [Pubmed]
  30. Role of ceramide in mediating the inhibition of telomerase activity in A549 human lung adenocarcinoma cells. Ogretmen, B., Schady, D., Usta, J., Wood, R., Kraveka, J.M., Luberto, C., Birbes, H., Hannun, Y.A., Obeid, L.M. J. Biol. Chem. (2001) [Pubmed]
  31. Modulation of EGF receptor activity by changes in the GM3 content in a human epidermoid carcinoma cell line, A431. Meuillet, E.J., Mania-Farnell, B., George, D., Inokuchi, J.I., Bremer, E.G. Exp. Cell Res. (2000) [Pubmed]
  32. Novel role of lactosylceramide in vascular endothelial growth factor-mediated angiogenesis in human endothelial cells. Rajesh, M., Kolmakova, A., Chatterjee, S. Circ. Res. (2005) [Pubmed]
  33. Dissociation of endogenous cellular ceramide from NF-kappa B activation. Betts, J.C., Agranoff, A.B., Nabel, G.J., Shayman, J.A. J. Biol. Chem. (1994) [Pubmed]
  34. Structural features of the UCCG and UGCG tetraloops in very short hairpins as evidenced by optical spectroscopy. Abdelkafi, M., Leulliot, N., Baumruk, V., Bednárová, L., Turpin, P.Y., Namane, A., Gouyette, C., Huynh-Dinh, T., Ghomi, M. Biochemistry (1998) [Pubmed]
  35. Ceramide formation during heat shock: a potential mediator of alpha B-crystallin transcription. Chang, Y., Abe, A., Shayman, J.A. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
 
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