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https://www.selleckchem.com/products/tideglusib.html Overexpression of SPNS2 or of MFSD2B, both known S1P efflux transporters, in TKO cells increased the direct uptake of S1P, whereas knockout of MFSD2B in TKO cells reduced this uptake. These results suggest that these are channel-type transporters and are capable of not only exporting, but also importing S1P. Furthermore, we observed that MEDEP-E14 cells, erythroid cells expressing MFSD2B, exhibited high S1P uptake activity. Our findings describing direct S1P uptake may contribute to the elucidation of the molecular mechanisms that regulate plasma S1P concentration.Organic anion transporter 1 (OAT1/SLC22A6) is a drug transporter with numerous xenobiotic and endogenous substrates. The Remote Sensing and Signaling Theory suggests that drug transporters with compatible ligand preferences can play a role in "organ crosstalk," mediating overall organismal communication. Other drug transporters are well known to transport lipids, but surprisingly little is known about the role of OAT1 in lipid metabolism. To explore this subject, we constructed a genome-scale metabolic model using omics data from the Oat1 knockout mouse. The model implicated OAT1 in the regulation of many classes of lipids, including fatty acids, bile acids, and prostaglandins. Accordingly, serum metabolomics of Oat1 knockout mice revealed increased polyunsaturated fatty acids, diacylglycerols, and long chain fatty acids, and decreased ceramides and bile acids when compared to wild type controls. Some aged knockout mice also displayed increased lipid droplets in the liver when compared to wild type mice. Chemoinformatics and machine learning analyses of these altered lipids defined molecular properties that form the structural basis for lipid-transporter interactions, including the number of rings, positive charge/volume, and complexity of the lipids. Finally, we obtained targeted serum metabolomics data after short-term treatment of rodents with the OAT
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