Glucosylceramide synthase

Liu, Y.Y., Han, T.Y., Giuhano, A.E. and Cabot, M.C., 1999, Expression of glucosylceramide synthase, converting ceramide to glucosylceramide, confers adriamycin resistance in human breast cancer cells. J. Biol. Chem. 274 1140-1146. 

Rani, C. S., Abe, A., Chang, Y., Rosenzweig, N., Saltiel, A. R., Radin, N. S., and Shayman, J. A., 1995, Cell cycle arrest induced by an inhibitor of glucosylceramide synthase. Correlation with cyclin-dependent kinases. J. Biol. Chem. 270 2859-2867. 

Miglustat (60 Zavesca ) 1 -Deoxynoj irimycin (DNJ) Iminosugar Semi-synthetic NP Microbial Type 1 Gaucher disease (GDI) Inhibits glucosylceramide synthase activity 215-217, 525-531... 

Fig. 2. Mechanisms causing resistance to antitumor treatment. ATM. ataxia telangiectasia gene, (Westphal et al., 1998 Xu and Baltimore, 1996), bcl-2/bax (Farrow and Brown, 1996, Zunino et al., 1997 Haq and Zanke, 1998), bcr/abl (McGahon et al., 1994), BCRP, breast cancer resistance protein (Doyle et d., 1998 Ross et al, 1999) bleomycin hydrolase (El-Deiry, 1997), BRCAl (Husain et al., 1998 Chen et al., 1998), BRCA2 (Chen et al., 1998 Chen et 1999), c-abl (White and Prives, 1999), c-jun (Sanchez-Perez and Perona, 1999), cytidine deaminase (El-Deiry, 1997), DNA poip, DNA polymerase p (Ochs et al., 1999), dihydrofolate reductase (Schimke, 1986), DT-diaphorase (Riley and Workman, 1992 Fitzsimmons et al., 1996 El-Deiry, 1997), EGR-1 (Ahmed et al., 1996), fos (Niimi et al., 1991), glucosylceramide synthase...

Inokuchi, J., Jimbo, M., Momosaki, K., Shimeno, H., Nagamatsu, A., and Radin, N. S. (1990). Inhibition of experimental metastasis of murine Lewis lung carcinoma by an inhibitor of glucosylceramide synthase and its possible mechanism of action. Cancer Res. 50, 6731-6737. 

Mizutani, A., Kuroda, Y., Muramoto, K., Kobayashi, K., Yamagishi, K., and Inokuchi, J. (1996). Effects of glucosylceramide synthase inhibitor and ganglioside GCMb on synchronous oscillations of intracellular Ca2+ in cultured cortical neurons. Biochem. Biophys. Res. Commun. 222, 494—498. 

Mutoh, T., Tokuda, A., Inokuchi, J., and Kuriyama, M. (1998). Glucosylceramide synthase inhibitor inhibits the action of nerve growth factor in PC 12 cells. J. Biol. Chem. 273, 26001—26007. 

Deng W, Li R, Guerrera M, Liu Y, Ladisch S. Transfection of glucosylceramide synthase antisense inhibits mouse melanoma formation. Glycobiology 2002 12 145-152. 

Ceramide formed in mammalian systems is metabolized to sphingomyelin, glycosphingolipids, and ceramide 1-phosphate by the actions of sphingomyelin synthase, glucosylceramide synthase, and ceramide kinase on ceramide, respectively. Ceramide synthesized in the endoplasmic reticulum is transported to the Golgi apparatus for synthesis of complex sphingolipids (93). Sphingomyelin is synthesized from ceramide by transfer of the... 

Figure 12 Structures of synthetic inhibitors of sphingomyelin synthase, ceramidases, p-glucosylceramide synthase, dihydroceramide desaturase, and SI P lyase.

Boucheron C, Desvergnes V, Compain P, Martin OR, Lavi A, Mackeen M, Wormald MR, Dwek RA, Butters TD. Design and synthesis of imino-sugar-based inhibitors of glucosylceramide synthase the search for new therapeutic agents against Gaucher disease. Tetrahedron Asymmetry 2005 16 1747-1756. 

Abe A, Inokuchi J, Jimbo M, Shimeno H, Nagamatsu A, Shayman JA, Shukla GS, Radin NS. Improved inhibitors of glucosylceramide synthase. J. Biochem. 1992 111 191-196. 

Gouaze, V., Liu, Y.Y., Prickett, C.S., Yu, J.Y., Giuliano, A.E., and Cabot, M.C. Glucosylceramide synthase blockade down-regulates P-glycoprotein and resensitizes multidrug-resistant breast cancer cells to anticancer drugs. Cancer Res, 65, 2005, 3861-3867. 

Norris-Cervetto, E., Callaghan, R., Platt, F.M., Dwek, R.A., and Butters, T.D. Inhibition of glucosylceramide synthase does not reverse drug resistance in cancer cells. J Biol Client, 219, 2004, 40412 0418. 

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