Bilberry extracts induce gene expression through the electrophile response element

Bilberry extracts induce gene expression through the electrophile response element
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DOI:
10.1207/s15327914nc5401_11
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发表时间:
2006-01-01
影响因子:
2.9
通讯作者:
Blomhoff, Rune
Blomhoff, Rune
中科院分区:
医学4区
文献类型:
--
作者:
Charlotte, Mari;Myhrstad, Wik;Blomhoff, Rune

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对于由例如身体活动/锻炼、热量限制或酒精产生的轻度应激诱导的解毒和抗氧化防御重要的许多基因可以通过引起生物体产生这种防御反应来提供健康益处。最近,这些防御的诱导也被归因于食用植物的植物化学物质或次级代谢产物。许多多酚类化合物,其中构成了这些植物化学物质的大部分,增加细胞水平的抗氧化剂,如谷胱甘肽和其他成分的解毒系统,通过反式激活基因含有亲电反应元件(EpRE)在其启动子。一个这样的基因,γ-谷氨酰半胱氨酸合成酶,以前已被证明是积极的调节槲皮素,黄酮类化合物中发现的高浓度洋葱,苹果,和越橘通过EpRE反式激活。作为进一步的步骤,我们已经研究了越橘和槲皮素是否具有诱导Fos相关抗原1(Fra-1)的转录的能力,Fos相关抗原1(Fra-1)在其启动子中含有两个EpRE Fra-1是转录因子激活蛋白1(AP-1)家族的成员,并且由于缺乏反式激活结构域Fra-1,可以抑制AP-1的激活。我们目前的结果表明,提取物从越橘,黄酮类槲皮素,丰富的越橘,诱导FRA-1启动子和细胞内容的FRA-1 mRNA。我们进一步提供证据表明,这种诱导是通过EpRE介导的。
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.