Regulation of Octn2 Transporter (SLC22A5) by Peroxisome Proliferator Activated Receptor Alpha(Biopharmacy)

概要

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The tissue distribution and disposition of carnitine, which plays an important role in the transport of longchain fatty acids across the mitochondrial inner membrane for β-oxidation, are well controlled by carnitine transporter organic cation/carnitine transporter 2 (OCTN2). Since little information is available on regulation of the expression of the OCTN2 gene, we examined the factors that affect the expression level of rat Octn2 (rOctn2), focusing on nuclear receptor peroxisome proliferator activated receptor alpha (PPARα), which regulates expression of genes associated with β-oxidation of fatty acids. mRNA of rOctn2 was induced by the PPARα ligand fenofibrate in primary-cultured rat hepatocytes. Further, the PPARα ligand Wy14643 increased the expression of Octn2 in wild-type mice, but not in PPARα knockout mice. Analysis of the rOctn2 promoter region suggested the presence of putative cis elements of PPARα. Wistar rats treated with intraperitoneal fenofibrate administration showed increased expression of rOctn2 mRNA in liver, and uptake of [^3H] carnitine by freshly isolated hepatocytes derived from those rats was also increased. In conclusion, our results indicate that the nuclear receptor PPARα directly up-regulates the expression of rOctn2 and increases the hepatic uptake of carnitine via rOctn2.
社団法人日本薬学会の論文
2008-06-01