Modulation of sphingolipid biosynthesis in primary cultured neurons by long chain bases

Sphingolipid biosynthesis was studied in cultured murine cerebellar cells in the absence and presence of exogenous sphingosine homologues with different alkyl chain lengths (12, 18, and 24 carbon atoms). Labeling of cells with [14C]serine for 24 h indicated that endogenous sphingosine biosynthesis w...

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Bibliographic Details
Published in:The Journal of biological chemistry 1990-06, Vol.265 (16), p.9333-9339
Main Authors: VAN ECHTEN, G, BIRK, R, BRENNER-WEISS, G, SCHMIDT, R. R, SANDHOFF, K
Format: Article
Language:English
Subjects:
Analytical, structural and metabolic biochemistry
Animals
Antigens, CD
Biological and medical sciences
Carbohydrate Sequence
Cell Survival - drug effects
Cells, Cultured
Cerebellum - cytology
Fundamental and applied biological sciences. Psychology
Galactose - metabolism
Gangliosides - metabolism
Glycosphingolipids - biosynthesis
Glycosphingolipids - metabolism
Lactosylceramides
Lipids
Mice
Molecular Sequence Data
Neurons - drug effects
Neurons - metabolism
Other biological molecules
Serine - metabolism
Sphingolipids
Sphingolipids - biosynthesis
Sphingosine - analogs & derivatives
Sphingosine - metabolism
Sphingosine - pharmacology
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Summary:Sphingolipid biosynthesis was studied in cultured murine cerebellar cells in the absence and presence of exogenous sphingosine homologues with different alkyl chain lengths (12, 18, and 24 carbon atoms). Labeling of cells with [14C]serine for 24 h indicated that endogenous sphingosine biosynthesis with incorporation of radiolabeled serine was inhibited by these long chain bases (0.5-50 microM) in a concentration-dependent manner; the inhibition was fully reversible after removal of the long chain bases from the culture medium. Metabolic labeling of neurons with [14C]galactose provided strong evidence that the cells were able to use the exogenous sphingosine homologues, irrespective of their alkyl chain length, as substrates for the biosynthesis of glycosphingolipids. When the biosynthetically inert sphingoid, azidosphingosine (5-50 microM), was fed to the cells, de novo sphingosine and glycosphingolipid biosynthesis were both strongly inhibited.
ISSN:0021-9258
1083-351X
DOI:10.1016/S0021-9258(19)38853-2