Blockade of the aryl hydrocarbon receptor pathway triggered by dioxin, polycyclic aromatic hydrocarbons and cigarette smoke by Phellinus linteus.
Blockade of the aryl hydrocarbon receptor pathway triggered by dioxin, polycyclic aromatic hydrocarbons and cigarette smoke by Phellinus linteus.
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DOI：
10.1248/bpb.31.1888
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发表时间：
2008-10
影响因子：
2
通讯作者：
Mai Mukai;A. Kasai;N. Hiramatsu;K. Hayakawa;Maro Okamura;Yasuhiro Tagawa;Jian Yao;Tomoyuki Nakamura;M. Kitamura
中科院分区：
文献类型：
--
作者：
Mai Mukai;A. Kasai;N. Hiramatsu;K. Hayakawa;Maro Okamura;Yasuhiro Tagawa;Jian Yao;Tomoyuki Nakamura;M. Kitamura
卤代烃和多环芳烃等环境污染物可激活芳烃受体（AhR），从而引起广泛的病理变化。AhR拮抗剂的开发将有助于预防和治疗与AhR活化相关的疾病。为此，我们在本研究中旨在利用分泌碱性磷酸酶（DRESSA）的二恶英响应元件传感技术，在菌丝提取物中寻找AhR通路的潜在抑制剂。通过对13个菌丝体的筛选，发现毛毛菌、蛹虫草和猴头菌的提取物对2,3,7,8-四氯二苯并-对二恶英、苯并[a]芘或3-甲基胆蒽具有抑制AhR活性的作用。随后的研究表明，只有毛毡草抑制所有这些激动剂引发的AhR和AhR依赖性基因表达的激活。众所周知，香烟烟雾中含有许多卤化和多环芳烃。我们发现茶树草有可能阻断香烟烟雾引发的AhR和AhR依赖性基因表达的激活。此外，茶树对AhR通路的抑制作用不依赖于；1) AhR或AhR核转运子的抑制，2)AhR抑制因子的诱导。我们得出结论，黄茶树含有有效的AhR激活抑制剂，可能有助于预防与AhR异常激活相关的病理。
Environmental pollutants including halogenated and polycyclic aromatic hydrocarbons activate the aryl hydrocarbon receptor (AhR) and thereby cause a wide range of pathological changes. Development of AhR antagonists will be useful for prevention and treatment of diseases related to AhR activation. Towards this end, we aimed in the present study at seeking for potential inhibitors of the AhR pathway in mycelial extracts using the dioxin responsive element-based sensing via secreted alkaline phosphatase (DRESSA). Through the screening of 13 mycelia, extracts prepared from Phellinus linteus, Cordyceps militaris and Hericium erinaceum inhibited activation of AhR by 2,3,7,8-tetrachlorodibenzo-p-dioxin, benzo[a]pyrene or 3-methylcholanthrene. Subsequent studies revealed that only Phellinus linteus suppressed activation of AhR and AhR-dependent gene expression triggered by all of these agonists. Cigarette smoke is known to contain a number of halogenated and polycyclic aromatic hydrocarbons. We found that Phellinus linteus has the potential to block activation of AhR and AhR-dependent gene expression triggered by cigarette smoke. Furthermore, the inhibitory effect of Phellinus linteus on the AhR pathway was independent of; 1) depression of AhR or AhR nuclear translocator, and 2) induction of AhR repressor. We conclude that Phellinus linteus contains potent inhibitor(s) of AhR activation and may be useful for prevention of pathologies associated with aberrant activation of AhR.