title: Bilberry extracts induce gene expression through the electrophile response element.
abstract: A number of genes important for detoxification and antioxidant defense induced by mild stress generated by, for example, physical activity/exercise, caloric restriction, or alcohol may provide health benefits by causing the organism to mount such a defense response. More recently, induction of these defenses has also been attributed to phytochemicals or secondary metabolites from dietary plants. Many polyphenols, which constitute a large fraction of these phytochemicals, increase cellular levels of antioxidants, such as glutathione and other components of the detoxification systems, via the transactivation of genes containing electrophile response elements (EpREs) within their promoters. One such gene, gamma-glutamylcysteine synthetase, has previously been shown to be positively regulated by quercetin, a flavonoid found in high concentrations in onions, apples, and bilberries through EpRE transactivation. As a further step, we have investigated whether bilberries and quercetin have the ability to induce transcription of Fos-related antigen 1 (Fra-1), which contains two EpREs in its promoter. Fra-1 is a member of the activator protein 1 (AP-1) family of transcription factors and, due to the lack of transactivation domain Fra-1, can suppress activation of AP-1. We present results demonstrating that extracts from bilberries, and the flavonoid quercetin, abundant in bilberries, induce the fra-1 promoter and the cellular content of Fra-1 mRNA. We further provide evidence that this induction is mediated through EpREs.
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Norway.
authors.forename: Mari Charlotte Wik
authors.initials: MC
authors.lastname: Myhrstad
authors.forename: Harald
authors.initials: H
authors.lastname: Carlsen
authors.forename: Linn Ingrid
authors.initials: LI
authors.lastname: Dahl
authors.forename: Kanae
authors.initials: K
authors.lastname: Ebihara
authors.forename: Line
authors.initials: L
authors.lastname: Glemmestad
authors.forename: Karin
authors.initials: K
authors.lastname: Haffner
authors.forename: Jan Øivind
authors.initials: JØ
authors.lastname: Moskaug
authors.forename: Rune
authors.initials: R
authors.lastname: Blomhoff
mesh_terms: D000818:Animals; D019556:COS Cells; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D005638:Fruit / Q000737:chemistry*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms; D010936:Plant Extracts / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D011794:Quercetin / Q000494:pharmacology; D020218:Response Elements / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D029800:Vaccinium myrtillus / Q000737:chemistry*; D000099169:Fos-Related Antigen 1
chemical_list: D010936:Plant Extracts; D016760:Proto-Oncogene Proteins c-fos; D011794:Quercetin; D000099169:Fos-Related Antigen 1