کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2597189 | 1562407 | 2008 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Cytochrome P450 2C11 5â²-flanking region and promoter: Regulation by aromatic hydrocarbons in vitro
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Cytochrome P450 2C11 5â²-flanking region and promoter: Regulation by aromatic hydrocarbons in vitro Cytochrome P450 2C11 5â²-flanking region and promoter: Regulation by aromatic hydrocarbons in vitro](/preview/png/2597189.png)
چکیده انگلیسی
Aromatic hydrocarbons elicit toxic and adaptive responses via the aryl hydrocarbon receptor (AHR). Aromatic hydrocarbons suppress the transcription of the growth hormone-regulated, male-specific rat hepatic cytochrome P450 2C11 gene (CYP2C11) in vivo via an unknown mechanism. We hypothesize that the suppression of CYP2C11 by aromatic hydrocarbons is mediated by the gene's promoter and 5â²-flanking region. Following bioinformatic analysis of putative transcription factor (TF) binding sites, we cloned extended lengths of the CYP2C11 5â²-flanking region into a promoterless luciferase plasmid. Suppression of CYP2C11 constructs was not observed upon treatment of transfected rat 5L, BP8 or mouse Hepa-1 cells with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 3-methylcholanthrene. In human HepG2 cells, the 10.1-kb construct displayed a pronounced 6- to 8-fold induction by TCDD. Deletion analysis localized the paradoxical induction response to a region between â1.8 kb and â1.3 kb, which contains a dioxin-responsive element (DRE) previously shown by us to be capable of binding activated AHR. This was confirmed by site-directed mutagenesis of the DRE. Induction of the 10.1-kb construct by TCDD in HepG2 cells was blocked by α-naphthoflavone, an AHR antagonist/partial agonist. The AHR is likely involved in the induction of CYP2C11-luciferase activity by TCDD in HepG2 cells and this response is at least partly DRE-mediated. Although CYP2C11 is suppressed by aromatic hydrocarbons in vivo, CYP2C11-luciferase constructs display a potentially misleading paradoxical induction in vitro that is cell-specific. Regulation of CYP2C11-luciferase plasmids is being studied in vivo in rat liver, where an intact endocrine system and the full complement of TFs needed for CYP2C11 suppression are present.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 248, Issues 2â3, 27 June 2008, Pages 104-112
Journal: Toxicology - Volume 248, Issues 2â3, 27 June 2008, Pages 104-112
نویسندگان
Rana M. Sawaya, David S. Riddick,