Abstract
Dihydro-sphingosine 1-phosphate (DH-S1P) is an analog of sphingosine 1-phosphate (S1P), which is a potent lysophospholipid mediator. DH-S1P has been proposed to exert physiological properties similar to S1P. Although S1P is known to be carried on HDL via apolipoprotein M (apoM), the association between DH-S1P and HDL/apoM has not been fully elucidated. Therefore, in the present study, we aimed to elucidate this association and to compare it with that of S1P and HDL/apoM. First, we investigated the distributions of S1P and DH-S1P among lipoproteins and lipoprotein-depleted fractions in human serum and plasma samples and observed that both S1P and DH-S1P were detected on HDL; furthermore, elevated amounts of DH-S1P in serum samples were distributed to the lipoprotein-depleted fraction to a greater degree than to the HDL fraction. Concordantly, a preference for HDL over albumin was only observed for S1P, and not for DH-S1P, when the molecules were secreted from platelets. Regarding the association with HDL, although both S1P and DH-S1P prefer to bind to HDL, HDL preferentially accepts S1P over DH-S1P. For the association with apoM, S1P was not detected on HDL obtained from apoM knockout mice, while DH-S1P was detected. Moreover, apoM retarded the degradation of S1P, but not of DH-S1P. These results suggest that S1P binds to HDL via apoM, while DH-S1P binds to HDL in a non-specific manner. Thus, DH-S1P is not a mere analog of S1P and might possess unique clinical significance.
Highlights
Sphingosine-1-phosphate (S1P) is a bioactive lysophospholipid mediator that exerts various physiological functions through S1P receptors located on cell surfaces, such as antiapoptosis [1], cell proliferation [2], vasorelaxation, and the maintenance of vascular permeability [3,4,5]
Regarding the dynamism of S1P in circulation, apolipoprotein M has crucial roles; the distribution of plasma S1P is unique compared with that of other lysophospholipids, with about two-thirds of S1P carried on HDL and the other one-third carried on albumin [10]
We investigated the difference between S1P and dihydro-sphingosine 1-phosphate (DH-S1P) in the kinetics of these sphingolipids, especially regarding their associations with apolipoprotein M (apoM)/HDL
Summary
Sphingosine-1-phosphate (S1P) is a bioactive lysophospholipid mediator that exerts various physiological functions through S1P receptors located on cell surfaces, such as antiapoptosis [1], cell proliferation [2], vasorelaxation, and the maintenance of vascular permeability [3,4,5]. Regarding the dynamism of S1P in circulation, apolipoprotein M (apoM) has crucial roles; the distribution of plasma S1P is unique compared with that of other lysophospholipids, with about two-thirds of S1P carried on HDL and the other one-third carried on albumin [10]. DH-S1P lacks one double bond in the 4-5 carbon position of S1P (Supplementary Figure S1), and its c 2018 The Author(s).
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