Novel transcriptional activities of vitamin E: inhibition of cholesterol biosynthesis.
Novel transcriptional activities of vitamin E: inhibition of cholesterol biosynthesis.
复制标题
维生素 E 的新型转录活性：抑制胆固醇生物合成。
DOI：
10.1021/bi701432q
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发表时间：
2008
期刊：
影响因子：
2.9
通讯作者：
Manor,Danny
中科院分区：
文献类型：
--
作者：
Valastyan,Scott;Thakur,Varsha;Johnson,Amy;Kumar,Karan;Manor,Danny
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)-α-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.
