کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5846929 | 1128549 | 2011 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Induction of cytochromes P450 1A1 and 1A2 by tanshinones in human HepG2 hepatoma cell line
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کلمات کلیدی
AHR7-ethoxyresorufin O-deethylationDihydrotanshinone ICYP1A2Tanshinone ICryptotanshinoneTIIADRETanshinone IIAARNTCYP1A1ERODBNFCyPCTSB[a]P - B [a] Pβ-naphthoflavone - β-naftoflavonearyl hydrocarbon receptor nuclear translocator - اتمسفر هسته ای گیرنده آرویل کربنInduction - القاءBenzo[a]pyrene - بنزو [a] پییرنtanshinone - تانشینونCytochrome P450 - سیتوکروم پی۴۵۰dioxin response element - عنصر پاسخ دیوکسینaryl hydrocarbon receptor - گیرنده آرویل هیدروکربن
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Diterpenoid tanshinones including tanshinone IIA (TIIA), cryptotanshinone (CTS), tanshinone I (TI) and dihydrotanshinone I (DHTI) are the major bioactive components from Danshen. The major aim of our present study was to investigate the induction potential of these four main components of tanshinones (TIIA, CTS, TI, and DHTI) on the expression of CYP1A1 and CYP1A2 in HepG2 cells. Our results showed that all of these four tanshinones caused a significant time- and concentration-dependent increase in the amount of CYP1A1/2 expression in HepG2 cells. These induction effects were further characterized through transcriptional regulation: the induction of CYP1A1/2 mRNA level by tanshinones was completely blocked by the transcription inhibitor actinomycin D; the expression of CYP1A1/2 heterogeneous nuclear RNA was induced by tanshinone treatment; and CYP1A1 mRNA stability was not influenced by these tanshinones. Interestingly, tanshinones plus B[a]P produced additive/synergistic effect on CYP1A1/2 induction. In addition, the tanshinone-induced CYP1A1/2 expression was abolished by the aryl hydrocarbon receptor (AhR) antagonist resveratrol, suggesting an AhR dependent transcription mechanism. In the reporter gene assay, while TI and DHTI significantly induced AhR-dependent luciferase activity, TIIA and CTS failed to induce this activity. Collectively, the tanshinones could induce CYP1A1 and CYP1A2 expression through transcriptional activation mechanism and exert differential effects on activating AhR in HepG2 cells. Our findings suggest that rational administration of tanshinones should be considered with respect to their effect on AhR and CYP1A1/2 expression.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 252, Issue 1, 1 April 2011, Pages 18-27
Journal: Toxicology and Applied Pharmacology - Volume 252, Issue 1, 1 April 2011, Pages 18-27
نویسندگان
Rong Zhang, Jianguo Sun, Liping Ma, Xiaolan Wu, Guoyu Pan, Haiping Hao, Fang Zhou, Jiye A, Changhui Liu, Hua Ai, Lili Shang, Haiyan Gao, Ying Peng, Ping Wan, Hui Wu, Guangji Wang,