کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5859452 1562347 2013 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Structure-dependent activities of hydroxylated polybrominated diphenyl ethers on human estrogen receptor
ترجمه فارسی عنوان
فعالیت های وابسته به ساختار از دیفنیل اترهای پلیبرومندی هیدروکسیل شده بر روی گیرنده استروژن انسان
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
چکیده انگلیسی
Polybrominated diphenyl ethers (PBDEs) have been shown to affect the estrogen receptor (ER) signaling pathway, and one of the proposed disruption mechanisms is direct binding of hydroxylated PBDE (OH-PBDE) to ER. In this paper, the binding affinity of 22 OH-PBDEs with different degrees of bromination to ER was assessed quantitatively using a surface plasmon resonance biosensor technique. Seven OH-PBDEs were found to bind directly with ER with KD ranging from 1.46 x 10−7 M to 7.90 x 10−6 M, and the affinity is in the order of 6-OH-BDE-047 ≧ 4′-OH-BDE-049 > 4′-OH-BDE-017 > 6′-OH-BDE-099 ≧ 5′-OH-BDE-099 > 2′-OH-BDE-007 > 3′-OH-BDE-028. In MVLN luciferase gene reporter assays, 10 low-brominated OH-PBDEs induced luciferase activity alone, but are 105 to 107 fold less potent than E2. Their estrogenic activity is in the order of 4′-OH-BDE-049 > 4′-OH-BDE-017 > 2′-OH-BDE-007 > 3′-OH-BDE-028 > 3-OH-BDE-047 ≧ 3′-OH-BDE-007. The good correlation between estrogenic activity and ER binding affinity of the low-brominated OH-PBDEs strongly suggest that these compounds induce ER transcriptional activity by binding directly with ER. The other 12 high-brominated OH-PBDEs inhibited luciferase activity of E2 to various degrees, demonstrating their antagonistic activity. Molecular docking analysis of the ER/OH-PBDE complexes revealed two distinctive binding modes between low- and high-brominated OH-PBDEs which provided rationale for the difference in their ER activity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 309, 5 July 2013, Pages 15-22
نویسندگان
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