The effects of serum Albumin on degradation and metabolism of S1P

Sphingosine-1-phosphate (S1P) is a lipid metabolite with multiple biological functions. The regulation of vascular permeability and control of immune cell trafficking are two elemental functions of S1P-S1P receptor (S1PR) signaling, which is related to the regulation of inflammation. The gradient of S1P concentration in plasma> lymph > tissue is essential for the maintenance of endothelial barrier function and other S1P dependent processes such as leukocyte trafficking. Therefore, the modulation of S1P degradation is a critical event for the S1P-S1PR signaling pathway. It is still largely unclear how S1P is bound to its chaperone serum albumin (SA) and how the SA influences the S1P-S1PR signaling axis. As one of the important chaperones for S1P, the effects of SA on degradation and metabolism of S1P were investigated. Cell culture experiments, liquid chromatography coupled to triple-quadrupole mass spectrometry (LC/MS/MS), spectrometric analyses, fluorescence-activated cell sorting (FACS) and Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) were used to investigate the effects of bovine serum albumin (BSA) and human serum albumin (HSA) on degradation and metabolism of S1P. Nuclear magnetic resonance (NMR) spectrometry was applied to determine the structure and interaction of S1P and SA in solution, After overnight incubation with (HTC4) wild type cells, S1P was protected from metabolism by BSA and HSA, but ovalbumin (OVA) did not provide such a protective effect. BSA was effectively hydrolyzed by pepsin. The pepsinized BSA and the non-protein part of BSA (NPBSA) cold not protect S1P from the metabolism of HTC4 cells. Serum albumin (SA) inhibited the extracellular dephosphorylation of S1P but did not influence the uptake of sphigosine (Sph) by HTC4 cells. BSA and HSA increased S1P induced S1PR1 internalization after overnight incubation with HTC4 cells, but OVA did not. ...



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