文章基本信息

标题：Preferential Blockade of Dioxin-Induced Activation of the Aryl Hydrocarbon Receptor by Antrodia camphorata
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作者：Mai Mukai ; Kunihiro Hayakawa ; Maro Okamura 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2009
卷号：32
期号：9
页码：1510-1515
DOI：10.1248/bpb.32.1510
出版社：The Pharmaceutical Society of Japan
摘要：Halogenated and polycyclic aromatic hydrocarbons are widely distributed pollutants in environments. These toxic substances activate the aryl hydrocarbon receptor (AhR) and thereby cause a broad spectrum of pathological changes. Development of AhR inhibitors will be useful for prevention of diseases caused by AhR activation. Using the dioxin responsive element (DRE)-based sensing via secreted alkaline phosphatase (DRESSA), we examined effects of Antrodia camphorata , a mycerial extract, on the activation of AhR by halogenated and polycyclic aromatic hydrocarbons. We found that Antrodia camphorata markedly suppressed activation of AhR triggered by 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD). In contrast, activation of AhR by polycyclic aromatic hydrocarbons (benzo[ a ]pyrene and 3-methylcholanthrene) was inhibited only modestly by this mycelium. Similarly, Antrodia camphorata only mildly attenuated activation of AhR by cigarette smoke that contains polycyclic aromatic hydrocarbons. Consistent with these results, Northern blot analysis revealed that DRE-driven exogenous and endogenous gene expression triggered by TCDD was abolished by Antrodia camphorata , whereas it did not substantially affect DRE-induced transcription triggered by benzo[ a ]pyrene, 3-methylcholanthrene or cigarette smoke. We also found that the inhibitory effect of Antrodia camphorata on TCDD-induced AhR activation was ascribed to neither down-regulation of AhR, down-regulation of the AhR nuclear translocator, nor up-regulation of the AhR repressor. These results suggest that Antrodia camphorata preferentially inhibits AhR activation and DRE-dependent gene expression triggered by dioxin.
关键词：aryl hydrocarbon receptor;Antrodia camphorata;dioxin;polycyclic aromatic hydrocarbon;cigarette smoke