Preferential blockade of dioxin-induced activation of the aryl hydrocarbon receptor by Antrodia camphorata.
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.
Mukai
Mai
M
Department of Molecular Signaling, University of Yamanashi, Chuo, Japan.
Hayakawa
Kunihiro
K
Okamura
Maro
M
Tagawa
Yasuhiro
Y
Nakajima
Shotaro
S
Saito
Yukinori
Y
Takahashi
Shuhei
S
Yao
Jian
J
Nishimura
Daisuke
D
Sugi
Masahito
M
Matsunaga
Masaji
M
Kitamura
Masanori
M
D000818:Animals; D055491:Antrodia / Q000737:chemistry / Q000502:physiology*; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018514:Plant Structures / Q000737:chemistry / Q000502:physiology*; D000072317:Polychlorinated Dibenzodioxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon