Sphingosine 1-Phosphate Distribution in Human Plasma: Associations with Lipid Profiles

Abstract

The physiological significance of sphingosine 1-phosphate (S1P) transport in blood has been debated. We have recently reported a comprehensive sphingolipid profile in human plasma and lipoprotein particles (VLDL, LDL, and HDL) using HPLC-MS/MS (Hammad et al., 2010). We now determined the relative concentrations of sphingolipids including S1P in the plasma subfraction containing lipoproteins compared to those in the remaining plasma proteins. Sphingomyelin and ceramide were predominantly recovered in the lipoprotein-containing fraction. Total plasma S1P concentration was positively correlated with S1P concentration in the protein-containing fraction, but not with S1P concentration in the lipoprotein-containing fraction. The percentage of S1P transported in plasma lipoproteins was positively correlated with HDL cholesterol (HDL-C) concentration; however, S1P transport in lipoproteins was not limited by the concentration of HDL-C in the individual subject. Thus, different plasma pools of S1P may have different contributions to S1P signaling in health and disease.

Sources, metabolism, and regulation of circulating sphingosine-1-phosphate

“…The remaining part binds to albumin (30-40%), LDLs ( ‫ف‬ 8%), and VLDLs (2-3%) ( 56,64 ). However, in some subjects more than 60% of S1P is transported by albumin ( 55 ). Although HDL is the major S1P carrier, there is no straightforward relationship between plasma HDL and total S1P level.…”

Microsomal Triglyceride Transfer Protein Transfers and Determines Plasma Concentrations of Ceramide and Sphingomyelin but Not Glycosylceramide

“…Sphingolipids are present in plasma associated with both B-lps and HDLs in nearly equal concentrations (23)(24)(25). Sphingosines and their 1-phosphates are associated with albumin and HDL (26). Higher levels of plasma sphingolipids are associated with various pathologies.…”

Accurate quantification of sphingosine-1-phosphate in normal and Fabry disease plasma, cells and tissues by LC-MS/MS with 13 C-encoded natural S1P as internal standard

“…1-Butanol was from Merck Millipore (Billerica, USA), ammonium formate from Sigma-Aldrich (St Louis, USA), sphingosine-1-phosphate (d17:1), sphingosine-1-phosphate (d18:1) and sphinganine-1-phosphate (d18:0) were from Avanti Polar Lipids (Alabaster, USA). Globotriaosylsphingosine (Lyso-Gb3) and [5][6][7][8][9] 13 C 5 -labeled lyso-Gb3 were earlier synthesized at the Leiden Institute of Chemistry (Leiden, The Netherlands) [32,33]. The synthesis of [5][6][7][8][9] 13 C 5 -labeled S1P is described below.…”

“…The level of S1P in blood and lymph is in the high nanomolar to low micromolar range, exceeding that in most cells and tissues [3]. In plasma, about 65% of S1P is bound to VLDL, LDL and HDL lipoproteins [4,5], most of which (~54%) is present in HDL, especially HDL3 [6][7][8]. S1P is known to fulfill important roles in various biological processes.…”

“…Interpretation of literature reports is complicated by the fact that quantification of plasma S1P is notoriously cumbersome and over time a vast number of different procedures have been employed for its measurement. The use of different analytical techniques by researchers might have contributes to the variations in reported ranges of S1P in plasma of normal individuals (200 to 840 nM) [4,5,8,21,22]. The quantification of S1P is challenging due to its zwitterion character, even more so the determination of relatively low levels in a complex matrix of other lipids.…”