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Volume 272, Number 5, Issue of January 31, 1997 pp. 3028-3035
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

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Elevation of Ceramide within Distal Neurites Inhibits Neurite Growth in Cultured Rat Sympathetic Neurons

(Received for publication, June 13, 1996, and in revised form, August 30, 1996)

From the ^a Lipid and Lipoprotein Research Group and the Departments of ^e Biochemistry, ^h Anatomy and Cell Biology, and ^c Medicine, University of Alberta, Edmonton, Alberta, T6G 2S2, Canada

Sphingolipids are abundant constituents of neuronal membranes and have been implicated in intracellular signaling. We show that two analogs of glycosphingolipid biosynthetic intermediates, fumonisin B₁ (which inhibits dihydroceramide synthesis) and DL-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP) (which inhibits glucosylceramide synthesis) decrease glycosphingolipid synthesis in rat sympathetic neurons. Although both fumonisin and PPMP inhibit glycosphingolipid synthesis, these inhibitors have differential effects on ceramide metabolism in axons. threo-PPMP, but not erythro-PPMP or fumonisin, induces an accumulation of [³H]palmitate-labeled ceramide and impairs axonal growth. Moreover, exogenously added, cell-permeable C₆-ceramide, but not C₆-dihydroceramide, mimicks the effect of PPMP. Our studies suggest that the lipid second messenger ceramide acts in distal axons, but not cell bodies, as a negative regulator of neurite growth.

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