Novel Transcriptional Activities of Vitamin E: Inhibition of Cholesterol Biosynthesis †

Cornell University, Ithaca, New York 14853, and Case Western Reserve University, Cleveland, Ohio 44106, USA.
Biochemistry (Impact Factor: 3.02). 02/2008; 47(2):744-52. DOI: 10.1021/bi701432q
Source: PubMed


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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    • "The beneficial effect of vitamin E on fetal growth could be mediated by the lowering of cholesterol. It has been shown recently that vitamin E can reduce cholesterol biosynthesis in vitro [43]. As well, vitamin E supplementation of rats and hamsters fed with atherogenic diets can reduce their plasma cholesterol levels [44] [45]. "
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    • "RV-induced inhibition of this kinase and its dependent pathways (p38 MAPK and JNK) significantly reduces influenza virus replication [105], so tocopherol's ability to suppress viral replication, independently from the antioxidant properties, might also depend on its interference with one/or more of these signalling cascades, which play important roles in the virus' lifecycle . To note that vitamin E is known to exert direct effects on the expression of genes that encode key enzymes in the cholesterol biosynthesis pathway [112]. "
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    • "f oxidative stress , however , may be counter - productive as increased membrane choles - terol may also increase Ab generation . However , another recent study has shown that vitamin E inhibits de novo cholesterol biosynthesis , by attenuating SREBP - 2 post - translational processing , thereby decreasing the effect of SREBP - 2 on target genes ( Valastyan et al . 2008 ) . Further studies are required to elucidate SREBP function pathways in cholesterol metabolism , and to establish any therapeutic value of anti - oxidants or drugs on SREBP function ."
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