Plasma sphingosine-1-phosphate measurement in healthy subjects: close correlation with red blood cell parameters

Ohkawa, Ryunosuke; Nakamura, Kazuhiro; Okubo, Shigeo; Hosogaya, Shigemi; Ozaki, Yukio; Tozuka, Minoru; Osima, Noriko; Yokota, Hiromitsu; Ikeda, Hitoshi; Yatomi, Yutaka

doi:10.1258/acb.2007.007189

Cited by 74 publications

(80 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, studies with ABC receptor knockout mice showed that neither ABCC1, ABCA1, nor ABCA7 contribute to plasma S1P levels (39). Nevertheless, these studies are consistent with recent findings in humans that plasma S1P levels positively correlate with erythrocyte levels (40). It has also recently been suggested that the vascular endothelium, in addition to the hematopoietic system, may also contribute to plasma S1P (37) and that ABCA1 and ABCC1 might be involved in S1P release from endothelial cells (39).…”

Section: The S1p Gradientsupporting

confidence: 84%

Sphingosine-1-phosphate: the Swiss army knife of sphingolipid signaling

Maceyka

Milstien

Spiegel

2009

Journal of Lipid Research

113

103

View full text Add to dashboard Cite

The sphingolipid metabolite sphingosine-1-phosphate (S1P) and the kinases that produce it have emerged as critical regulators of numerous fundamental biological processes important for health and disease. Activation of sphingosine kinases (SphKs) by a variety of agonists increases intracellular S1P, which in turn can be secreted out of the cell and bind to and signal through S1P receptors (S1PRs) in an autocrine and/or paracrine manner. Recent studies suggest that this "inside-out" signaling by S1P may play a role in many human diseases. As the roles of the S1PRs in cell and organismal physiology are discussed elsewhere in this volume, we focus this review mainly on recent reports showing how SphKs are activated and S1P reaches its receptors, the role of SphKs and S1P in regulating sphingolipid homeostasis, and the potential importance of the SphK/S1P axis as a therapeutic target in human diseases. Sphingolipids are ubiquitous components of all membranes in eukaryotic cells. Analogous to the lipid signaling molecules derived from metabolism of glycerolipids, sphingolipids produce bioactive sphingolipid metabolites such as sphingosine, sphingosine-1-phosphate (S1P), ceramide, and ceramide-1-phosphate that have key roles in regulating many important physiological and pathological functions (1). Signal-induced activation of several types of sphingomyelinases generates ceramide in a variety of compartments within the cell. Deacylation of ceramide by ceramidases yields sphingosine, the most common sphingoid base in mammals. Sphingoid bases can be recycled into complex sphingolipids or phosphorylated by one of two sphingosine kinase isozymes (SphK1 and SphK2) to form S1P. There are two pathways of S1P degradation: reversible dephosphorylation to sphingosine by nonspecific phosphatases, including lysosomal and lipid-specific phosphatases, and by two S1P-specific phosphatases, SPP1 and SPP2; and irreversible cleavage by S1P lyase (SPL), which can lead to the formation of phosphatidylethanolamine. The latter is the only pathway for degradation of sphingoid bases in mammalian cells.Ceramide, sphingosine, and S1P are readily interconvertable, which is of great significance not only because they are potent signaling molecules, but they also regulate cell growth and survival in different manners. Ceramide and sphingosine are important regulatory components of stress responses, typically inducing growth arrest and apoptosis (1). Conversely, S1P inhibits apoptosis and promotes proliferation (2). Thus, the dynamic balance between S1P and its precursors, ceramide and sphingosine, and their consequent regulation of opposing signaling pathways is an important factor that determines cell fate (3). Although many of the effects of S1P result from its action as a ligand for a family of five G protein-coupled receptors, denoted S1P 1-5 , there is some evidence indicating that S1P can also act through still not yet well-characterized intracellular targets (2). COULD S1P BE A CENTRAL REGULATOR OF SPHINGOLIPID METABOLISM?Many stu...

show abstract

Section: The S1p Gradientsupporting

confidence: 84%

Sphingosine-1-phosphate: the Swiss army knife of sphingolipid signaling

Maceyka

Milstien

Spiegel

2009

Journal of Lipid Research

113

103

View full text Add to dashboard Cite

show abstract

“…One study showed that plasma S1P level is higher in males than in females ( 62 ), whereas another study found the opposite in both mice and humans ( 63 ). However, other authors did not observe any gender difference ( 52,56 ).…”

Section: Plateletsmentioning

confidence: 96%

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

Książek

Chacińska

Chabowski

et al. 2015

Journal of Lipid Research

127

126

View full text Add to dashboard Cite

“…We therefore investigated the impact of apoM on two other potential pathways of S1P metabolism, namely effl ux from erythrocytes and urinary excretion. Plasma concentrations of S1P were recently shown to correlate with red blood cell counts ( 5,6,14 ), probably because the lack of the S1P-degrading lyase makes erythrocytes the main source of S1P in plasma ( 4,5 ). Because HDL was previously found to induce S1P effl ux from erythrocytes ( 5 ), we compared the S1P effl ux capacity of HDL from wild-type (wt), Apom…”

Section: S1p Effl Ux From Erythrocytesmentioning

confidence: 99%

Apolipoprotein M modulates erythrocyte efflux and tubular reabsorption of sphingosine-1-phosphate

Sutter

Park

Othman

et al. 2014

Journal of Lipid Research

View full text Add to dashboard Cite

This article is available online at http://www.jlr.org Supplementary key words high density lipoprotein • kidney • megalin • chloride-proton exchanger ClC5 • cystinosin Sphingosine-1-phosphate (S1P) acts both as an intracellular signaling molecule and an extracellular agonist of at least fi ve different G protein-coupled receptors. By its dual functions, S1P regulates the survival, proliferation, and migration as well as the functionality of many cells, eventually in opposite directions ( 1-4 ). Therefore the absolute and relative abundance of S1P in intracellular and extracellular compartments appears to be important for its biological functionality ( 4 ).Most cells form S1P by the phosphorylation of sphingosine, a degradation product of ceramides, through sphingosine kinase and degrade S1P to phosphoethanolamine and fatty aldehyde through S1P-lyase ( 1-4 ). By contrast, not only erythrocytes and platelets, but also other cells which have low or no lyase activity, release S1P ( 4-6 ), probably by an as yet unidentifi ed ABC transporter ( 4,7,8 ). Within the plasma compartment, the majority of S1P is transported by HDLs in which it exerts many cyto-protective and anti-infl ammatory effects, for example, on endothelial cells ( 8-10 ). The enrichment of S1P in HDL has been explained by the presence of a specifi c S1P binding protein, namely apoM ( 10 ). Purifi ed and recombinant apoM binds S1P with an IC 50 of 0.9 mol/l, which is in the range of physiological S1P plasma concentrations ( 11 ). X-ray crystallography of apoM identifi ed an S1P binding domain which was confi rmed by the recombinant generation of non-S1P binding apoM mutants ( 11 ). In agreement with these physicochemical data, S1P was copurifi ed with apoM containing HDL, but not apoM-free HDL, from both human Abstract Sphingosine-1-phosphate (S1P) mediates several cytoprotective functions of HDL. apoM acts as a S1P binding protein in HDL. Erythrocytes are the major source of S1P in plasma. After glomerular fi ltration, apoM is endocytosed in the proximal renal tubules. Human or murine HDL elicited time-and dose-dependent S1P effl ux from erythrocytes. Compared with HDL of wild-type (wt) mice, S1P effl ux was enhanced in the presence of HDL from apoM transgenic mice, but not diminished in the presence of HDL from apoM knockout ( Apom ؊ / ؊ ) mice. Artifi cially reconstituted and apoM-free HDL also effectively induced S1P effl ux from erythrocytes. S1P and apoM were not measurable in the urine of wt mice. Apom ؊ / ؊ mice excreted signifi cant amounts of S1P. apoM was detected in the urine of mice with defective tubular endocytosis because of knockout of the LDL receptor-related protein, chloride-proton exchanger ClC-5 ( Clcn5 ؊ / ؊ ), or the cysteine transporter cystinosin. Urinary levels of S1P were signifi cantly elevated in Clcn5 ؊ / ؊ mice. In contrast to Apom ؊ / ؊ mice, these mice showed normal plasma concentrations for apoM and S1P. In conclusion, HDL facilitates S1P effl ux from erythrocytes by both apoMdependent and apoM-independent mechanisms...

show abstract

Plasma sphingosine-1-phosphate measurement in healthy subjects: close correlation with red blood cell parameters

Cited by 74 publications

References 39 publications

Sphingosine-1-phosphate: the Swiss army knife of sphingolipid signaling

Sphingosine-1-phosphate: the Swiss army knife of sphingolipid signaling

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

Apolipoprotein M modulates erythrocyte efflux and tubular reabsorption of sphingosine-1-phosphate

Contact Info

Product

Resources

About