کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2595922 | 1562360 | 2012 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Novel 2-amino-isoflavones exhibit aryl hydrocarbon receptor agonist or antagonist activity in a species/cell-specific context
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کلمات کلیدی
AHRqRT-PCRTCDDChr2,3,7,8-Tetrachlorodibenzo-p-dioxin - 2،3،7،8-تترا کلریدیبنزوپتوفان دیوکسینIsoflavone - ایزوفلاونDioxin - دیوکسینquantitative real-time polymerase chain reaction - واکنش زنجیره ای پلیمراز کمی زمان واقعی استSpecies-specific - گونه های خاصaryl hydrocarbon receptor - گیرنده آرویل هیدروکربنAryl hydrocarbon receptor (AhR) - گیرنده هیدروکربن آریل (AhR)
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
The aryl hydrocarbon receptor (AhR) mediates the induction of a variety of xenobiotic metabolism genes. Activation of the AhR occurs through binding to a group of structurally diverse compounds, most notably dioxins, which are exogenous ligands. Isoflavones are part of a family which include some well characterised endogenous AhR ligands. This paper analysed a novel family of these compounds, based on the structure of 2-amino-isoflavone. Initially two luciferase-based cell models, mouse H1L6.1c2 and human HG2L6.1c3, were used to identify whether the compounds had AhR agonistic and/or antagonistic properties. This analysis showed that some of the compounds were weak agonists in mouse and antagonists in human. Further analysis of two of the compounds, Chr-13 and Chr-19, was conducted using quantitative real-time PCR in rat H4IIE and human MCF-7 cells. The results indicated that Chr-13 was an agonist in rat but an antagonist in human cells. Chr-19 was shown to be an agonist in rat but more interestingly, a partial agonist in human. Luciferase induction results not only revealed that subtle differences in the structure of the compound could produce species-specific differences in response but also dictated the ability of the compound to be an AhR agonist or antagonist. Substituted 2-amino-isoflavones represent a novel group of AhR ligands that must differentially interact with the AhR ligand binding domain to produce their species-specific agonist or antagonist activity and future ligand binding analysis and docking studies with these compounds may provide insights into the differential mechanisms of action of structurally similar compounds.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 297, Issues 1â3, 16 July 2012, Pages 26-33
Journal: Toxicology - Volume 297, Issues 1â3, 16 July 2012, Pages 26-33
نویسندگان
Richard J. Wall, Guochun He, Michael S. Denison, Cenzo Congiu, Valentina Onnis, Alwyn Fernandes, David R. Bell, Martin Rose, J. Craig Rowlands, Gianfranco Balboni, Ian R. Mellor,