Application Notes:
Dihydrosphingosine-1-phosphate (DhS1P) is the saturated analog of the more common sphingosine-1-phosphate (S1P) and
has recently been found to have many important and unique functions. It has been found to activate ERK1/2 and to stimulate
MMP1 production. DhS1P induces MMP1 (a key enzyme in matrix degradation) while S1P does not1 and S1P enhances
TGF-beta through cross-activation of Smad signaling while DhS1P inhibits it.2 DhS1P or its derivatives have been suggested
as effective therapeutic antifibrotic agents. Because of their unique actions in vivo DhS1P can be used as a negative control
for S1P for intracellular effects. However, DhS1P is a ligand for many S1P receptors. It has been found that SK1
overexpression, but not SK2, in different primary cells and cultured cell lines results in predominant upregulation of the
synthesis of DhS1P compared to S1P. A new functional role for SK1 has been presented, which can control the
survival/death (DhS1P-S1P/ceramides) balance by targeting sphingolipid de novo biosynthesis and selectively generating
DhS1P at a metabolic step preceding ceramide formation.3
References:
1. S. Bu et al. “Dihydrosphingosine 1-phosphate stimulates MMP1 gene expression via activation of ERK1/2-Ets1 pathway in human fibroblasts” The
FASEB Journal, Vol. 20(1) pp. 184-186, 2006
2. S. Bu et al. “Opposite Effects of Dihydrosphingosine 1-Phosphate and Sphingosine 1-Phosphate on Transforming Growth Factor-_/Smad Signaling Are
Mediated through the PTEN/PPM1A-dependent Pathway” Journal of Biological Chemistry, Vol. 283(28) pp. 19593-19602, 2008
3. E. Berdyshe “De novo biosynthesis of dihydrosphingosine-1-phosphate by sphingosine kinase 1 in mammalian cells” Cellular Signaling, Vol. 18(10) pp.
1779-1792, 2006