ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: We reported previously that stereoisomers of 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), the d-threo and l-threo forms, exerted inhibitory and stimulatory effects on glycosphingolipid (GSL) biosynthesis in B16 melanoma cells, respectively. In the present study, the primary cultured rat neocortical explants were treated with l- or d-threo-PDMP. These isomers exhibited opposite effects on neurite outgrowth: d-PDMP was inhibitory at concentrations ranging from 5 to 20 µM, whereas l-PDMP was stimulatory over the same concentration range, and the maximal effect was observed at 10–15 µM. Rat neocortical explants were doubly labeled with [14C]serine and [3H]galactose at 15 µMl- or d-PDMP. l-PDMP increased the incorporations of both labels into sphinganine, sphingosine, ceramide, sphingomyelin, neutral GSLs, and gangliosides, whereas d-PDMP inhibited the glucosylation of ceramide resulting in a reduction of ganglioside biosynthesis and accumulation of precursors of glucosylceramide, ceramide, and sphingomyelin. To clarify the stimulatory effect of l-PDMP on GSL biosynthesis, serine palmitoyltransferase, sphingosine N-acyltransferase, glucosylceramide synthase, lactosylceramide synthase, GM3 synthase, and GD3 synthase were quantified in cell lysates of explants pretreated with this agent. Serine palmitoyltransferase was fully activated up to 150% of the control. Furthermore, marked increases in the activities of lactosylceramide synthase (200%), GM3 synthase (240%), and GD3 synthase (300%) were observed. These results suggest that the neurotrophic action of l-PDMP may be ascribable to its stimulatory effect on the biosynthesis of GSLs, especially that of gangliosides.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.1996.67051821.x
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