کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2478967 1113414 2014 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Comparative Studies of Human UDP-glucuronosyltransferase 1A8 and 1A9 Proximal Promoters Using Single Base Substitutions
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Comparative Studies of Human UDP-glucuronosyltransferase 1A8 and 1A9 Proximal Promoters Using Single Base Substitutions
چکیده انگلیسی
The nucleotide sequences of the proximal promoters of UDP-glucuronosyltransferase (UGT) 1A8 and 1A9 genes are very similar. However, UGT1A8 and 1A9 are mainly expressed in extra-hepatic and hepatic cells, respectively. Using mutants of UGT1A8 and 1A9 proximal promoters, we revealed their critical differences in terms of promoter activity and the role of the T-repeat region (T-region) conserved in both promoters. In extra-hepatic cells, Caco2, the activity of UGT1A9 proximal promoter increased to 73.4 ± 8.5% of that of the UGT1A8 proximal promoter with only 4 base changes: -160C, -152A, -62T, and -59G. The derivatives of the T-region showed that this region is not necessary for promoter activity, but the length of T repeats influences the activity somewhat. Therefore, the cause of the low activity of the UGT1A9 proximal promoter may be not only 4 base changes, but also the truncation of T repeats. From these results, the UGT1A9 proximal promoter was assumed to change into the non-active form from the original sequence, and this might be one of the reasons for the tissue-specific expression of UGT1A9.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Drug Metabolism and Pharmacokinetics - Volume 29, Issue 1, 2014, Pages 90-93
نویسندگان
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