Novel transcriptional activities of vitamin E: inhibition of cholesterol biosynthesis.
Vitamin E is a dietary lipid that is essential for vertebrate health and fertility. The biological activity of vitamin E is thought to reflect its ability to quench oxygen- and carbon-based free radicals and thus to protect the organism from oxidative damage. However, recent reports suggest that vitamin E may also display other biological activities. Here, to examine possible mechanisms that may underlie such nonclassical activities of vitamin E, we investigated the possibility that it functions as a specific modulator of gene expression. We show that treatment of cultured hepatocytes with (RRR)-alpha-tocopherol alters the expression of multiple genes and that these effects are distinct from those elicited by another antioxidant. Genes modulated by vitamin E include those that encode key enzymes in the cholesterol biosynthetic pathway. Correspondingly, vitamin E caused a pronounced inhibition of de novo cholesterol biosynthesis. The transcriptional activities of vitamin E were mediated by attenuating the post-translational processing of the transcription factor SREBP-2 that, in turn, led to a decreased transcriptional activity of sterol-responsive elements in the promoters of target genes. These observations indicate that vitamin E possesses novel transcriptional activities that affect fundamental biological processes. Cross talk between tocopherol levels and cholesterol status may be an important facet of the biological activities of vitamin E.
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- alpha-Tocopherol
- Vitamin E
- Transcription, Genetic
- Sterol Regulatory Element Binding Protein 2
- Serum Response Element
- Reproducibility of Results
- Reactive Oxygen Species
- Protein Processing, Post-Translational
- Oligonucleotide Array Sequence Analysis
- Multigene Family
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- alpha-Tocopherol
- Vitamin E
- Transcription, Genetic
- Sterol Regulatory Element Binding Protein 2
- Serum Response Element
- Reproducibility of Results
- Reactive Oxygen Species
- Protein Processing, Post-Translational
- Oligonucleotide Array Sequence Analysis
- Multigene Family