Cho, Joo-Youn; Kang, Dong Wook; Ma, Xiaochao; Ahn, Sung-Hoon; Krausz, Kristopher W; Luecke, Hans; Idle, Jeffrey R; Gonzalez, Frank J (2009). Metabolomics reveals a novel vitamin E metabolite and attenuated vitamin E metabolism upon PXR activation. Journal of lipid research, 50(5), pp. 924-37. Bethesda, Md.: American Society for Biochemistry and Molecular Biology ASBMB 10.1194/jlr.M800647-JLR200
Full text not available from this repository. (Request a copy)Pregnane X receptor (PXR) is an important nuclear receptor xenosensor that regulates the expression of metabolic enzymes and transporters involved in the metabolism of xenobiotics and endobiotics. In this study, ultra-performance liquid chromatography (UPLC) coupled with electrospray time-of-flight mass spectrometry (TOFMS), revealed altered urinary metabolomes in both Pxr-null and wild-type mice treated with the mouse PXR activator pregnenolone 16alpha-carbonitrile (PCN). Multivariate data analysis revealed that PCN significantly attenuated the urinary vitamin E metabolite alpha-carboxyethyl hydroxychroman (CEHC) glucuronide together with a novel metabolite in wild-type but not Pxr-null mice. Deconjugation experiments with beta-glucuronidase and beta-glucosidase suggested that the novel urinary metabolite was gamma-CEHC beta-D-glucoside (Glc). The identity of gamma-CEHC Glc was confirmed by chemical synthesis and by comparing tandem mass fragmentation of the urinary metabolite with the authentic standard. The lower urinary CEHC was likely due to PXR-mediated repression of hepatic sterol carrier protein 2 involved in peroxisomal beta-oxidation of branched-chain fatty acids (BCFA). Using a combination of metabolomic analysis and a genetically modified mouse model, this study revealed that activation of PXR results in attenuated levels of the two vitamin E conjugates, and identification of a novel vitamin E metabolite, gamma-CEHC Glc. Activation of PXR results in attenuated levels of the two vitamin E conjugates that may be useful as biomarkers of PXR activation.
Item Type: |
Journal Article (Original Article) |
|---|---|
ISSN: |
0022-2275 |
Publisher: |
American Society for Biochemistry and Molecular Biology ASBMB |
Language: |
English |
Submitter: |
Factscience Import |
Date Deposited: |
04 Oct 2013 15:10 |
Last Modified: |
04 May 2014 23:22 |
Publisher DOI: |
10.1194/jlr.M800647-JLR200 |
PubMed ID: |
19141872 |
Web of Science ID: |
000264969300017 |
URI: |
https://boris.unibe.ch/id/eprint/30848 (FactScience: 195183) |
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