Effect of drugs and temperature on biosynthesis and transport of glycosphingolipids in cultured neurotumor cells |
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Authors: | Halina Miller-Prodraza Peter H. Fishman |
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Affiliation: | Membrane Biochemistry Section, Developmental and Metabolic Neurology Branch, N.I.N.C.D.S., National Institutes of Health, Bethesda, MD 20205 U.S.A. |
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Abstract: | Neuroblastoma and glioma cells were grown in the presence of [3H]galactose, and the incorporation of 3H into gangliosides and the transport of newly synthesized gangliosides to the cell surface were examined under different experimental conditions. A variety of drugs, including inhibitors of protein synthesis and energy metabolism, modulators of the cytoskeleton and the ionophore monensin, had no effect on the transport of newly synthesized GD1a in neuroblastoma cells. Only low temperature effectively blocked translocation to the plasma membrane. Monensin, however, had marked effects on the biosynthesis of gangliosides and neutral glycosphingolipids. Whereas incorporation of 3H into complex glycosphingolipids was reduced, labeling of glucosylceramide was increased in cells exposed to monensin. In addition, biosynthesis of the latter glycolipid was less susceptible to low temperatures than that of more complex ones. Previous studies have implicated the Golgi apparatus as the predominant site of glycosylation of gangliosides. As monensin has been reported to interfere with the Golgi apparatus, our results indicate that glucosylceramide may be synthesized at a site that is separate from the site where further glycosylation occurs. Once synthesis of a ganglioside is completed, transport of the molecule to the cell surface proceeds under conditions of cytoskeletal disruption, energy depletion and ionic inbalance, but not low temperature. |
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Keywords: | Glycosphingolipid synthesis Lipid transport Drug Monensin (Neurotumor cell) GM3 GM2 GM1 GD1a GlcCer glucosylceramide LacCer lactosylceramide Galα1-4Galβ1-4Glcβ1-1′Cer GalNacβ1-3Galα1-4Galβ1-4Glcβ1-1′Cer DNP-GD1a dinitrophenolhydrazine derivative of GD1a |
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