کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2581215 | 1130178 | 2010 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
TSU-16, (Z)-3-[(2,4-dimethylpyrrol-5-yl)methylidenyl]-2-indolinone, is a potent activator of aryl hydrocarbon receptor and increases CYP1A1 and CYP1A2 expression in human hepatocytes
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کلمات کلیدی
RT-PCRKHBOMPU0126SP600125ethoxyresorufin-O-deethylaseTCDDVEGFRERODKrebs–Henseleit bufferXREPD98059CyP3MC3-methylcholanthreneCYP inductionFBSDMEMHHMAHR1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene2,3,7,8-Tetrachlorodibenzo-p-dioxin - 2،3،7،8-تترا کلریدیبنزوپتوفان دیوکسینBSA - BSADulbecco's modified Eagle's medium - Medal of Eagle اصلاح شده DulbeccosiRNA - siRNAligand binding assay - آزمایش لیگاند اتصالbovine serum albumin - آلبومین سرم گاوOmeprazole - امپرازولfetal bovine serum - سرم جنین گاوCytochrome P450 - سیتوکروم پی۴۵۰xenobiotic-responsive element - عنصر واکنش زنجبیلVascular endothelial growth factor - فاکتور رشد اندوتلیال عروقیVascular Endothelial Growth Factor (VEGF) - فاکتور رشد اندوتلیال عروقی (VEGF)reverse transcription-polymerase chain reaction - واکنش زنجیره ای رونویسی-پلیمراز معکوسaryl hydrocarbon receptor - گیرنده آرویل هیدروکربنvascular endothelial growth factor receptor - گیرنده فاکتور رشد اندوتلیال عروقی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: TSU-16, (Z)-3-[(2,4-dimethylpyrrol-5-yl)methylidenyl]-2-indolinone, is a potent activator of aryl hydrocarbon receptor and increases CYP1A1 and CYP1A2 expression in human hepatocytes TSU-16, (Z)-3-[(2,4-dimethylpyrrol-5-yl)methylidenyl]-2-indolinone, is a potent activator of aryl hydrocarbon receptor and increases CYP1A1 and CYP1A2 expression in human hepatocytes](/preview/png/2581215.png)
چکیده انگلیسی
(Z)-3-[(2,4-dimethylpyrrol-5-yl)methylidenyl]-2-indolinone (TSU-16), is a potent anti-angiogenic agent that inhibits the tyrosine kinase of vascular endothelial growth factor receptor-2. In clinical trials with daily or twice weekly intravenous administration of TSU-16, its increased clearance was observed. To understand the mechanism underlying this observation, we have investigated the TSU-16-mediated regulation of cytochrome P450 expression. In human hepatocytes, TSU-16 increased mRNA levels of CYP1A1 and CYP1A2, but not CYP2B6 and CYP3A4. The extent of increase and profiles of the time-dependent changes in CYP1A1 and CYP1A2 mRNA levels after TSU-16 treatment were similar to those after treatment with 3-methylcholanthrene (3MC), a well-known activator of the aryl hydrocarbon receptor (AhR). In reporter assays using a plasmid construct that contained the human CYP1A1 5â²-flanking region including the region crucial for the AhR-dependent transcription of both human CYP1A1 and CYP1A2, TSU-16 treatment increased reporter activities to an extent similar to that obtained with 3MC. Treatment of HepG2 cells and human hepatocytes with AhR-targeting siRNA suppressed the increase in both mRNA levels and CYP1A activities after treatment with TSU-16 as well as after that with omeprazole or 3MC. TSU-16 also time-dependently reduced cellular AhR protein levels in HepG2 cells to a similar extent with 3MC treatment. Furthermore, we demonstrated that unlabeled TSU-16 and 3MC but not omeprazole completely inhibited the specific binding of [3H]-3MC to mouse Hepa1c1c7 cytosol, suggesting TSU-16 as an AhR ligand. In conclusion, our present results suggest that TSU-16 binds to and activates AhR to enhance the expression of both human CYP1A1 and CYP1A2. Because TSU-16 is metabolized mainly by CYP1A2, its increased clearance after repeated dosing may be attributed to the enhanced expression of hepatic CYP1A2.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemico-Biological Interactions - Volume 185, Issue 1, 15 April 2010, Pages 33-41
Journal: Chemico-Biological Interactions - Volume 185, Issue 1, 15 April 2010, Pages 33-41
نویسندگان
Kazuaki Matsuoka-Kawano, Kouichi Yoshinari, Sekio Nagayama, Yasushi Yamazoe,