Abstract
The nuclear receptor liver X receptor (LXR) plays an important role in the metabolism and homeostasis of cholesterol, lipids, bile acids, and steroid hormones. In this study, we uncovered a function of LXRα (NR1H3) in regulating the human hydroxysteroid sulfotransferase SULT2A1, a phase II conjugating enzyme known to sulfonate bile acids, hydroxysteroid dehydroepiandrosterone, and related androgens. We showed that activation of LXR induced the expression of SULT2A1 at mRNA, protein, and enzymatic levels. A combination of promoter reporter gene and chromatin immunoprecipitation assays showed that LXRα transactivated the SULT2A1 gene promoter through its specific binding to the −500- to −258-base pair region of the SULT2A1 gene promoter. LXR small interfering RNA knockdown experiments suggested that LXRα, but not LXRβ, played a dominant role in regulating SULT2A1. In primary human hepatocytes, we found a positive correlation between the expression of SULT2A1 and LXRα, which further supported the regulation of SULT2A1 by LXRα. In summary, our results established human SULT2A1 as a novel LXRα target gene. The expression of LXRα is a potential predictor for the expression of SULT2A1 in human liver.
Footnotes
- Received April 4, 2014.
- Accepted July 15, 2014.
This work was supported in part by the National Institutes of Health grants [Grants R01-DK083952, R01-DK099232, and R01-HD073070] to W.X. and Visiting Student Scholarships from the Government of China’s China Scholarship Council to Z.O. [No. 2008638059] and B.H. [No. 201206380045]. Normal human hepatocytes were obtained through the Liver Tissue Procurement and Distribution System, Pittsburgh, PA, which was funded by the National Institutes of Health [Contract N01-DK-7-0004/HHSN267200700004C].
- Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
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