title: Novel transcriptional activities of vitamin E: inhibition of cholesterol biosynthesis.
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.
authors: Cornell University, Ithaca, New York 14853, and Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors: Scott
authors: S
authors: Valastyan
authors: Varsha
authors: V
authors: Thakur
authors: Amy
authors: A
authors: Johnson
authors: Karan
authors: K
authors: Kumar
authors: Danny
authors: D
authors: Manor
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D002784:Cholesterol / Q000096:biosynthesis*; D006224:Cricetinae; D003412:Cricetulus; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015203:Reproducibility of Results; D027602:Serum Response Element; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014810:Vitamin E / Q000494:pharmacology*; D024502:alpha-Tocopherol / Q000494:pharmacology
chemical_list: D017382:Reactive Oxygen Species; D051782:Sterol Regulatory Element Binding Protein 2; D014810:Vitamin E; D002784:Cholesterol; D024502:alpha-Tocopherol; D000111:Acetylcysteine