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The regulation of sphingosine-1-phosphate metabolism

     Sphingosine-1-phosphate (S1P) is a signaling sphingolipid and is also referred to as a bioactive lipid mediator. Functions of S1P are mediated by its binding to a class of G-protein coupled receptors of the S1P and Lysophospholipid (LPA) receptor families, and regulate a variety of cell signaling pathways, including cell growth, differentiation, survival, and apoptosis. Many factors in the metabolism pathway of S1P have been considered as potential targets for therapeutic intervention, including the inhibition of S1P activation of the G-protein coupled receptors.

     Previous studies have indicated that regulation of SIP is mainly mediated by the enzymatic pathways responsible for S1P degradation. Recently, some researchers begin to put insights into the loss in potency of S1P by in vitro pharmacological inhibition.
     In a latest paper, Bradley and the colleagues reported their study about the subject. The [35S]-GTPγS binding is considered to be a functional assay for the accurate determination of antagonist affinity constants and mechanism of action, and the result shows that the potency of S1P decreases when incubated with CHO-S1P2 membranes. Then, the inclusion of a phosphatase inhibitor cocktail prevents inhibition of potency of S1P In the [35S]-GTPγS binding assay. Further analysis of the individual components of PIC2 is carried out, and two of the components, sodium molybdate and sodium orthovanadate were found to inhibit S1P degradation[1].
     Taken together, S1P is mainly mediated by two kinds of ways: enzymatic pathways and pharmacological inhibition. Thus, the factors that is involved in the two pathways may be the potential target in the diseases related to the metabolism of S1P. 

Reference

[1]. Eur. J. Pharmacol. (2011), doi:10.1016/j.ejphar.2011.09.178.

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