The metabolism of exogenous gangliosides in the CNS has been investigated using cerebellar granule cells in culture as a model. For this purpose, GM2 and GM1, both isotopically radiolabeled at the level of the terminal sugar residue or of the long chain base moiety, were administered to differentiated cells for a 15-h pulse, and their metabolic fate was followed in a time course protocol. At each time investigated (1, 2, and 4 days after the pulse), several compounds, besides the ones administered, were detected: (a) GM2 (only after GM1 was given), GM3, lactosylceramide, glucosylceramide, and ceramide, all products of ganglioside stepwise catabolism; (b) GM1 (only after GM2 was given), GD1a, GD1b, O-Ac-GT1b, and GT1b, that is, gangliosides more complex than the one administered; and (c) sphingomyelin. The compounds derived from ganglioside catabolism and sphingomyelin were detected only after administration of long chain base-labeled precursors, whereas the others were found regardless of the labeling position of the precursor. In addition, radioactivity was incorporated in the delipidized residue when sugar-labeled gangliosides were given to cells. Besides qualitative differences, quantitative ones were found after administration of the different precursors. Comparison of differences in the radioactivity incorporation values and calculation of the specific radioactivity of the individual sugar components of the GD1a and GT1b formed led to the conclusions that exogenous gangliosides (a) are easily taken up and metabolized by cerebellar granule cells, (b) undergo catabolism following the conventional pathway, (c) can be utilized directly as substrates for glycosylating reactions, thus giving rise to more complex gangliosides, and (d) give rise to fragments (of either saccharide or lipid nature) that can escape complete degradation and be reutilized for the resynthesis of gangliosides and sphingomyelin. This recycling process seems to be more efficient for lipid-carrying fragments than for sugar-containing fragments.
|Number of pages||8|
|Journal||Journal of Neurochemistry|
|Publication status||Published - 1989|
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience