Article

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

ABSTRACT

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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    • "In the lungs of male and female mice cytoskeleton genes such as myosin heavy chain, α-actin, and tropomyosin were up-regulated (Oommen et al., 2007). Among the most prominent pathways affected by vitamin E were those related to inflammatory response (Lin et al., 2002; Han et al., 2006; Vasu et al., 2007) and cholesterol metabolism (Pal et al., 2003; Valastyan et al., 2008). Research conducted in our laboratory in Boer goats showed that dietary supplementation of vitamin E improved the development of reproductive organs (Zhu et al., 2009) and protected the testes from damage by peroxidation (Zhu et al., 2010). "
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    Full-text · Dataset · Jan 2016
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    • "In the lungs of male and female mice cytoskeleton genes such as myosin heavy chain, α-actin, and tropomyosin were up-regulated (Oommen et al., 2007). Among the most prominent pathways affected by vitamin E were those related to inflammatory response (Lin et al., 2002; Han et al., 2006; Vasu et al., 2007) and cholesterol metabolism (Pal et al., 2003; Valastyan et al., 2008). Research conducted in our laboratory in Boer goats showed that dietary supplementation of vitamin E improved the development of reproductive organs (Zhu et al., 2009) and protected the testes from damage by peroxidation (Zhu et al., 2010). "
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    ABSTRACT: Gene-chip technology was employed to study the effect of dietary vitamin E on gene expression in sheep testes based on our previous research. Thirty-five male Tan sheep (20-30days after weaning) with similar body weight were randomly allocated into five groups and supplemented 0, 20, 100, 200 and 2000IU·sheep(-1)day(-1) vitamin E (treatments denoted as E0, E20, E100, E200, and E2000, respectively) for 120days. At the end of the study the sheep were slaughtered and the testis samples were immediately collected and stored in liquid nitrogen. Differences in gene expression between different treated groups were identified. Based on GO enrichment analysis and the KEGG database to evaluate the gene expression data we found that vitamin E might affect genes in the testes by modulating the oxidation level, by affecting the expression of various receptors and transcription factors in biological pathways, and by regulating the expression of metabolism-associated genes. The effect of vitamin E supplementation on the expression of oxidative enzyme-related genes was detected by quantitative real-time PCR (qRT-PCR) and Western blot. The results show that dietary vitamin E, at various doses, can significantly increase (P<0.05) the mRNA and protein expression of Glutathione peroxidase 3 and Glutathione S-transferase alpha 1. In addition, the results of qRT-PCR of the antioxidant enzyme genes were consistent with those obtained using the gene chip microarray analysis. In summary, the dietary vitamin E treatment altered the expression of a number of genes in sheep testes. The increase in the mRNA and protein levels of antioxidant enzyme genes, coupled with the elevation in the activity of the antioxidant enzymes were primarily responsible for the improved reproductive performance promoted by dietary vitamin E.
    Full-text · Article · Jan 2016 · Gene
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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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    ABSTRACT: The susceptibility to develop atherosclerosis is increased by intrauterine growth restriction and prenatal exposure to maternal hypercholesterolemia. Here, we studied whether mouse gestational hypercholesterolemia and atherosclerosis affected fetal development and growth at different stages of gestation. Female LDLR KO mice fed a proatherogenic, high cholesterol (HC) diet for 3 weeks before conception and during pregnancy exhibited a significant increase in non-HDL cholesterol and developed atherosclerosis. At embryonic days 12.5 (E12.5), E15.5, and E18.5, maternal gestational hypercholesterolemia and atherosclerosis were associated to a 22-24% reduction in male and female fetal weight without alterations in fetal number/litter or morphology nor placental weight or structure. Feeding the HC diet exclusively at the periconceptional period did not alter fetal growth, suggesting that maternal hypercholesterolemia affected fetal weight only after implantation. Vitamin E supplementation (1,000 UI of α-tocopherol/kg) of HC-fed females did not change the mean weight of E18.5 fetuses but reduced the percentage of fetuses exhibiting body weights below the 10th percentile of weight (HC: 90% vs. HC/VitE: 68%). In conclusion, our results showed that maternal gestational hypercholesterolemia and atherosclerosis in mice were associated to early onset fetal growth restriction and that dietary vitamin E supplementation had a beneficial impact on this condition.
    Full-text · Article · Sep 2014 · BioMed Research International
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