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Distinct generation, pharmacology, and distribution of sphingosine 1‐phosphate and dihydro‐sphingosine 1‐phosphate in human neural progenitor cells
Author(s) -
Callihan Phillip,
Zitomer Nicholas C.,
Stoeling Michael V.,
Kennedy Perry C.,
Lynch Kevin R,
Riley Ronald T.,
Hooks Shelley B.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.674.3
Subject(s) - sphingosine , sphingosine 1 phosphate , sphingosine 1 phosphate receptor , microbiology and biotechnology , ceramide , biology , receptor , neural stem cell , sphingolipid , chemistry , pharmacology , biochemistry , stem cell , apoptosis
Studies suggest a crucial role for Sphingosine 1‐phosphate (S1P) and its receptors in nervous system development. Dihydrosphingosine 1‐phosphate (dhS1P), a reduced form of S1P, is an agonist at S1P receptors, but the biology of dhS1P has not been widely studied. The mycotoxin fumonisin B1 (FB 1 ) is a potent inhibitor of ceramide synthases and causes selective accumulation of dihydrosphingosine and dhS1P. Maternal exposure to FB 1 correlates with the development of neural tube defects in which the neural epithelial progenitor cells of the developing brain fail to fuse. We hypothesize that the altered balance of S1P and dhS1P in neural epithelial cells contributes to the developmental effects of FB 1 . We defined the effect of FB 1 exposure on levels of sphingosine and dh‐sphingosine and their receptor active 1‐phosphates in human neural progenitor (hES‐NEP) cells, and the relative activity of dhS1P and S1P in these cells. We found that dhS1P is a more potent stimulator of inhibition of cAMP and Smad phosphorylation than is S1P, and this difference in apparent potency may be due, in part, to more persistent presence of extracellular dhS1P applied to hES‐NEP cells rather than a higher activity at S1P receptors. This study establishes hES‐NEP cells as a useful human in vitro model system to study FB 1 toxicity and the molecular pharmacology of sphingolipid signaling. Research supported by: NIH & UGA Research Foundation