کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5510568 | 1539262 | 2017 | 36 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Regulation of hepatic abcb4 and cyp3a65 gene expression and multidrug/multixenobiotic resistance (MDR/MXR) functional activity in the model teleost, Danio rerio (zebrafish)
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کلمات کلیدی
PCNtime of maximum concentrationPregnane X-receptorpregnenolone 16α-carbonitrileCYP450P-gpPXRtmaxABCCyPARMAXCmaxP-glycoprotein - P-گلیکوپروتئینmaximum concentration - حداکثر غلظتBiotransformation - زیستدگرگونیCytochrome P450 - سیتوکروم پی۴۵۰Efflux - فلوکسFish - ماهیKetoconazole - کتوکونازولATP-binding cassette - کیت اتصال به ATP
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Multidrug/multixenobiotic resistance (MDR/MXR) confers resistance to a diverse range of potentially toxic pharmaceuticals and environmental contaminants through a cellular response that involves the coordinated induction and activity of the ATP-binding cassette (ABC) transporter P-glycoprotein (P-gp) and the Phase I metabolizing enzyme cytochrome P450 3A (CYP3A). In mammals, ligand-mediated pregnane X receptor (PXR) transcriptional activity regulates the induction of P-gp and CYP3A; however, this mechanism has not been well-characterized in piscine species. Zebrafish (Danio rerio) treated with the Pxr agonist pregnenolone 16α-carbonitrile (PCN) showed decreased P-gp (zebrafish Abcb4) and CYP3A (zebrafish Cyp3a65) mRNA levels after 48 h exposure; however, treatment with PCN also resulted in increased hepatic MDR/MXR functional activity (i.e. increased Rhodamine 123 efflux) in vivo. Consistent with mammalian-like MDR/MXR regulated by PXR, the PCN-mediated modulation of hepatic Abcb4 and Cyp3a65 mRNA levels and MDR/MXR functional activity was attenuated by co-treatment with PCN and the mammalian PXR antagonist, ketoconazole (KTC). These results provide evidence that zebrafish Pxr may play a role in MDR/MXR through transcriptional regulation of abcb4 and cyp3a65 gene expression.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology - Volume 200, October 2017, Pages 34-41
Journal: Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology - Volume 200, October 2017, Pages 34-41
نویسندگان
Jeremy S. Jackson, Christopher J. Kennedy,