کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2487917 | 1114440 | 2006 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A Novel MDR1 G1199T Variant Alters Drug Resistance and Efflux Transport Activity of P-Glycoprotein in Recombinant Hek Cells
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: A Novel MDR1 G1199T Variant Alters Drug Resistance and Efflux Transport Activity of P-Glycoprotein in Recombinant Hek Cells A Novel MDR1 G1199T Variant Alters Drug Resistance and Efflux Transport Activity of P-Glycoprotein in Recombinant Hek Cells](/preview/png/2487917.png)
چکیده انگلیسی
The human multidrug resistance gene MDR1 encodes the protein product P-glycoprotein (P-gp). P-gp is an integral membrane protein which mediates ATP-dependent substrate efflux. We recently discovered a novel GâââT variant at 1199 nucleotide position of MDR1 which exhibits a 2.3% allelic frequency in leukemia patients. The functional effects of this MDR1-G1199T variant were evaluated with recombinant HEK cells that stably express the wild-type, G1199A, or G1199T variant of the MDR1 protein, P-gp, at comparable levels. A panel of cytotoxic P-gp substrates comprising doxorubicin, vinblastine, vincristine, paclitaxel, or topotecan (a poor P-gp substrate) was used to evaluate the functional impact of G1199 variations. Compared to MDR1wt, MDR1G1199A exhibited an increased resistance to doxorubicin, paclitaxel, vinblastine, and vincristine. In contrast, MDR1G1199T reduced resistance to ¼ that of MDR1wt for all drugs except topotecan. Expression of MDR1 exhibits some degree of resistance to topotecan, but 1199 variation has no impact. These data were consistent with the variation in intracellular doxorubicin concentrations measured in MDR1 recombinant cells. Our results suggest that patients with the novel MDR1-G1199T variant may exhibit a lower degree of MDR1 dependent chemoresistance, and those with the G1199A polymorphism may exhibit a higher degree of resistance, compared with MDR1 wild-type patients.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 95, Issue 12, December 2006, Pages 2767-2777
Journal: Journal of Pharmaceutical Sciences - Volume 95, Issue 12, December 2006, Pages 2767-2777
نویسندگان
Matthew H. Crouthamel, Daniel Wu, Ziping Yang, Rodney J.Y. Ho,