Journal
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
Volume 24, Issue 12, Pages 2158-2167Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2013.08.008
Keywords
alpha-Tocopherol; alpha-Tocopherol transfer protein (alpha-TTP); Liver X receptor (LXR); Lipogenesis
Funding
- Japan Society for the Promotion of Science [21591336, 24591530]
- Morinaga Foundation
- Mother and Child Health Foundation
- Food Science Institute Foundation
- Mishima Kaiun Memorial Foundation
- Osaka Medical Research Foundation for Incurable Disease
- Grants-in-Aid for Scientific Research [24591530, 21591336] Funding Source: KAKEN
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Fat-soluble vitamin E (alpha-tocopherol) has antioxidant activity. alpha-Tocopherol transfer protein (alpha-TIP), a hepatic cytosolic protein, selectively binds alpha-tocopherol and has an important role regulating circulatory alpha-tocopherol levels. However, only a few studies have shown the transcriptional regulation of the alpha-TTP gene. Here, we demonstrate that liver X receptor (LXR) regulates alpha-TTP expression through direct interaction with the alpha-TTP gene promoter, and it modulates circulating alpha-tocopherol levels. LXR belongs to the nuclear receptor superfamily, acts as a ligand-dependent transcription factor for oxysterols and plays an important role in cholesterol metabolism and lipogenesis. We identified an LXR response element (LXRE; DR4, a direct repeat with four-nucleotides spacing) of the human alpha-TTP gene promoter by using luciferase and electrophoretic mobility shift assays. Mutations in this element abolished activation of this promoter. Moreover, treatment of vitamin E-deficient rats with T0901317, a synthetic LXR ligand, increased alpha-TTP expression in the liver and cerebrum and increased the plasma alpha-tocopherol levels. These results indicate that the LXR signaling pathway modulates alpha-TTP gene expression and plasma alpha-tocopherol levels. Our observations imply that the LXR signaling pathway might be a useful target for antioxidant properties by controlling the vitamin E status. (C) 2013 Elsevier Inc. All rights reserved.
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