Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
|
pubmed:dateCreated |
1996-12-2
|
pubmed:abstractText |
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 microM, whereas L-PDMP was stimulatory over the same concentration range, and the maximal effect was observed at 10-15 microM. Rat neocortical explants were doubly labeled with [14C]serine and [3H]galactose at 15 microM L- 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.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carbon Radioisotopes,
http://linkedlifedata.com/resource/pubmed/chemical/Ceramides,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Galactose,
http://linkedlifedata.com/resource/pubmed/chemical/Gangliosides,
http://linkedlifedata.com/resource/pubmed/chemical/Glycosphingolipids,
http://linkedlifedata.com/resource/pubmed/chemical/Morpholines,
http://linkedlifedata.com/resource/pubmed/chemical/RV 538,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Sphingomyelins,
http://linkedlifedata.com/resource/pubmed/chemical/Sphingosine,
http://linkedlifedata.com/resource/pubmed/chemical/Tritium,
http://linkedlifedata.com/resource/pubmed/chemical/safingol
|
pubmed:status |
MEDLINE
|
pubmed:month |
Nov
|
pubmed:issn |
0022-3042
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:volume |
67
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
1821-30
|
pubmed:dateRevised |
2007-11-15
|
pubmed:meshHeading |
pubmed-meshheading:8863486-Animals,
pubmed-meshheading:8863486-Carbon Radioisotopes,
pubmed-meshheading:8863486-Cells, Cultured,
pubmed-meshheading:8863486-Ceramides,
pubmed-meshheading:8863486-Embryo, Mammalian,
pubmed-meshheading:8863486-Enzyme Inhibitors,
pubmed-meshheading:8863486-Female,
pubmed-meshheading:8863486-Galactose,
pubmed-meshheading:8863486-Gangliosides,
pubmed-meshheading:8863486-Glycosphingolipids,
pubmed-meshheading:8863486-Humans,
pubmed-meshheading:8863486-Kinetics,
pubmed-meshheading:8863486-Morpholines,
pubmed-meshheading:8863486-Neurites,
pubmed-meshheading:8863486-Neurons,
pubmed-meshheading:8863486-Pregnancy,
pubmed-meshheading:8863486-Radioisotope Dilution Technique,
pubmed-meshheading:8863486-Rats,
pubmed-meshheading:8863486-Rats, Wistar,
pubmed-meshheading:8863486-Serine,
pubmed-meshheading:8863486-Sphingomyelins,
pubmed-meshheading:8863486-Sphingosine,
pubmed-meshheading:8863486-Stereoisomerism,
pubmed-meshheading:8863486-Tritium
|
pubmed:year |
1996
|
pubmed:articleTitle |
Induction of ganglioside biosynthesis and neurite outgrowth of primary cultured neurons by L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol.
|
pubmed:affiliation |
Tokyo Research Institute, Seikagaku Corporation, Japan.
|
pubmed:publicationType |
Journal Article
|