GLYCOSPHINGOLIPIDS IN FETAL TAY-SACHS DISEASE BRAIN AND LUNG CULTURES |
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| Authors: | Linda M Hoffman D Amsterdam S E Brooks L Schneck |
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| Institution: | Neuroscience Center of the Kingsbrook Jewish Medical Center and the Downstate Medical Center of the State University of New York, Brooklyn, NY 11203, U.S.A. |
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| Abstract: | Abstract— A study was undertaken of the glycosphingolipids in cell cultures derived from cerebellum of Tay-Sachs disease fetal brain in order to determine the suitability of such cell strains as a model for Tay-Sachs disease. The glycosphingolipids in the Tay-Sachs disease cultured cerebellar cells were compared with those found in normal cultured cerebellar cells, normal and Tay-Sachs cultured lung cells, and normal and Tay-Sachs fetal brain. The glycolipids were separated by TLC, then analyzed by GLC of the trimethylsilyi derivatives of the methylglycosides of the sugar moieties. In the cultured cerebellar lines, the predominant gangliosides were GM2, GM3, and GD3. There was a 4-fold increase of GM2 in the Tay-Sachs as compared with the normal line. Only GM3 and GD3 gangliosides were found in the Tay-Sachs and the normal fetal lung cell cultures. The major neutral glycosphingolipids in all of the cultured cells which were analyzed were glucosylceramide, lactosylceramide, digalactosyl-glucosylceramide, and globoside. When the Tay-Sachs cerebellar cells were labelled with 1-14C]gluco-samine, some radioactivity was observed in the trihexosylceramide band, indicating the presence of a small amount of a galactosamine-containing trihexosylceramide which may be asialo-GM2 (GA2). The trihexosylceramide in Tay-Sachs fetal brain was identified as GA2 by GLC. Both Tay-Sachs and normal fetal brain gangliosides were more complex than those found in the cultured cells. Long chain fatty acids (C24:0 and C24;1) predominated in all of the glycosphingolipids of the Tay-Sachs and the normal cultured cerebellar cells. In contrast, the glycosphingolipids of Tay-Sachs and normal fetal brain contained mainly the shorter chain fatty acids (C16:0, C18:0, and C18:1). The cerebrosides in both the Tay-Sachs and normal fetal brains were mainly glucosylceramide with only small amounts of the galactosylceramide which predominates in infant brain. Cultured cells from the fetal Tay-Sachs disease |
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