• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2003년도 추계국제학술대회
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• pp.179-179
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• 2003

Exposure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes a variety of biological and toxicology effects, most of which are mediated by aryl hydrocarbon receptor (AhR). The ligand-bound AhR as a heterodimer with AhR nuclear translocator (ARNT) binds to its specific DNA recognition site, the dioxin-responsive element (DRE), and it results in increased transcription of CYP1A1 gene. Retinoic acid (RA) regulates the transcription of various genes for several essential functions through binding to two classes of nuclear receptors, the retinoic acid receptor (RAR) and retinoid X receptor (RXR). Constitutive androstane receptor (CAR) also regulates the transcription of gene. In this study, we have examined how RAR, RXR and CAR regulated CYP1A1 in rainbow trout hepatoma cell (RTH 149) using luciferase reporter gene assay system. We did transient transfection with CYP1A1 luciferase reporter gene and treated with TCDD, all-trans RA, 9-cis RA and phenobarbital. Treatment of all-trans RA, 9-cis RA or phenobarbital decreased the TCDD induced transcription of CYP1A1. When we did transient cotransfection with CYP1A1 luciferase reporter gene and RXR, as increase of RXR concentration, the TCDD induced transcription of CYP1A1 was decreased. Transfection with CAR also decreased the TCDD induced transcription of CYP1A1 in RTH 149 cells.

• Environmental Analysis Health and Toxicology
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• 제21권1호
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• pp.13-19
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• 2006

화학적 예방효과가 있는 식물성 에스트로젠은 다양한 환성을 나타내며 여러 세포 수용체와 상호작용한다. Genistein은 isoflavone의 주요물질 중의 하나로 콩류에 존재하며 대표적인 식물성 에스트로젠이다. 본 논문에서는 유방암 세포주인 MCF-7에서 aryl hydrocarbon receptor(AhR)에 의해 매개되는 발암물질 활성화 경로에 대한 genistein의 영향을 살펴보았다. 세포에 genistein을 처리할 경우 cytochrome P450 1A1(CYP1A1) 약물대사효소의 특이적인 효소반응인 7-ethoxyresorufin O-deethylase (EROD) 활성도와 CYP1A1의 유전자 발현이 genistein의 농도 의존적으로 증가하였다. Genistein과 발암물질인 방향족탄화 수소 7, 12-dimethylbenz[a]anthracene(DMBA)를 동시 처리하였을 경우 DMBA에 의해 유도되어 증가된 EROD활성도와 CYP1A1의 유전자 발현이 genistein에 의해 감소하였다. 랫트의 간에서 분리한 세포질을 이용하여 genistein과 AhR의 대표적인 ligand인 2,3,7,8-tetrachlorodibenzo-p-dioxin과 경쟁적 결합에 대한 영향을 조사한 결과 genistein이 AhR에 경쟁적으로 결합함을 알 수 있었다. 이러한 결과들은 genistein이 천연 AhR ligand임을 암시한다. 따라서, 식물성 에스트로젠인 genistein은 AhR경로의 길항제/항진제로 작용할 수 있을 것으로 사료된다.

• Archives of Pharmacal Research
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• 제29권7호
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• pp.570-576
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• 2006

Phytoestrogen biochanin A is an isoflavone derivative isolated from red clover Trifolium pratense with anticarcinogenic properties. This study examined the action of biochanin A with the carcinogen activation pathway that is mediated by the aryl hydrocarbon receptor (AhR) in MCF-7 breast carcinoma cells. Treating the cells with biochanin A alone caused the accumulation of CYP1A1 mRNA and an increase in CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity in a dose dependent manner. A concomitant treatment with 7,12-dimethylbenz[a]anthracene (DMBA) and biochanin A markedly reduced the DMBA-inducible EROD activity and CYP1A1 mRNA level. In addition, the biochanin A treatment alone activated the DNA-binding capacity of the AhR for the dioxin-response element (DRE) of CYP1A1, as measured by the electrophoretic-mobility shift assay (EMSA). EMSA revealed that biochanin A reduced the level of the DMBA-inducible AhR-DRE binding complex. Furthermore, biochanin A competed with the prototypical AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), for binding to the AhR in an isolated rat cytosol. The biochanin A competitively inhibited the metabolic activation of DMBA, as measured by the formation of the DMBA-DNA adducts. These results suggest that biochanin A may thus be a natural ligand to bind on AhR. Therefore, biochanin A may be due to act an antagonist/agonist of the AhR pathway.

• Environmental Analysis Health and Toxicology
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• 제14권3호
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• pp.103-111
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• 1999

To effectively predict the lipophilicity, the aryl hydrocarbon receptor (AhR) affinity, and TEF (Toxic equivalency factor) of dioxins by geometrical descriptors, the multiple linear regression methods with the forward selection and backward elimination were employed with statistical validity. The lipophilicity, the Ah receptor binding affinity, and the toxic equivalency factor of dioxins could be predicted using some geometrical descriptors.

• Biomolecules & Therapeutics
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• 제27권6호
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• pp.570-576
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• 2019

Particulate matter (PM), which refers to the mixture of particles present in the air, can have harmful effects. Damage to cells by PM, including disruption of organelles and proteins, can trigger autophagy, and the relationship between autophagy and PM has been well studied. However, the cellular regulators of PM-induced autophagy have not been well characterized, especially in keratinocytes. The Aryl Hydrocarbon Receptor (AhR) is expressed in the epidermis and is activated by PM. In this study, we investigated the role of the AhR in PM-induced autophagy in HaCaT cells. Our results showed that PM led to AhR activation in keratinocytes. Activation of the AhR-target gene CYP1A1 by PM was reduced by co-treatment with ${\alpha}$-naphthoflavone (${\alpha}-NF$), an AhR inhibitor. We also evaluated activation of the autophagy pathway in PM-treated keratinocytes. In HaCaT cells, treatment with PM treatment led to the induction of microtubules-associated proteins light chain 3 (LC3) and p62/SQSTM1, which are essential components of the autophagy pathway. To study the role of the AhR in mediating PM-induced autophagy, we treated cells with ${\alpha}-NF$ or used an siRNA against AhR. Expression of LC3-II induced by PM was decreased in a dose dependent manner by ${\alpha}-NF$. Furthermore, knockdown of AhR with siAhR diminished PM-induced expression of LC3-II and p62. Together, these results suggest that inhibition of the AhR decreases PM-induced autophagy. We confirmed these results using the autophagy-inhibitors BAF and 3-MA. Taken together, our results indicate that exposure to PM induces autophagy via the AhR in HaCaT keratinocytes.

• Bulletin of the Korean Chemical Society
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• 제28권2호
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• pp.285-291
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• 2007

The 5-HT6 antagonists are mainly related to the treatment of cognitive dysfunction or impairment associated with Alzheimer's disease and schizophrenia. There have been lots of efforts to develop 5-HT6 antagonists. As in our efforts, arylsulfonylpiperazine derivatives 1-3 were designed, synthesized and biologically evaluated against the human recombinant 5-HT6 serotonin receptor. Total 36 compounds were synthesized and the most active compound among the synthesized compounds is compound 2h with an IC50 value of 1.5 μM. The compound 2h is novel as 5-HT6 receptor ligand and could act as lead for the novel 5-HT6 receptor ligands.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Dietary and Medicinal Antimutgens and Anticarcinogens
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• pp.186-186
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• 2001

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental toxin that activates the aryl hydrocarbon receptor (AhR) and disrupts multiple endocrine signaling pathways by enhancing ligand metabolism, altering hormone synthesis, down regulating receptor levels, and interfering with gene transcription. And TCDD-mediated gene transactivation via the AhR has been shown to be dependent upon estrogen receptor (ER) expression in human breast cancer cells.(omitted)

• Journal of Yeungnam Medical Science
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• 제25권1호
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• pp.41-49
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• 2008

한탄바이러스가 혈소판활성인자 활성에 영향을 미치는지 알아보기 위하여 간접적으로 혈소판활성인자 수용체의 발현과 분해효소의 활성을 측정하였다. 혈관내피세포에서 혈소판활성인자 수용체의 유전자를 역전사 중합효소연쇄반응으로, 단백질은 western blot으로 측정하였다. 또한 세포표면에 발현된 혈소판활성인자 수용체의 양은 FACS로 분석하였다. 한탄바이러스에 감염된 혈관내피세포에서 혈소판활성인자 수용체의 유전자, 단백질, 세포 표면의 발현 모두 바이러스에 감염되지 않은 대조 세포보다 감염 후 2, 3일째 증가 하였다. 혈액 내 혈소판활성인자 분해효소의 활성을 비교한 결과 신증후출혈열 환자에서 정상인에 비하여 2.5배 낮았다. 그리고 신증후출혈열 환자가 회복됨에 따라 혈소판활성인자의 활성이 다시 정상 수준으로 회복되는 것으로 나타났다. 따라서 한탄바이러스에 의해 증가된 혈소판활성인자 수용체의 발현이 혈소판활성인자와 혈관내피세포와 반응성을 증가시키고, 신증후출혈열 환자 혈액에서 감소된 혈소판활성인자 분해효소가 혈소판활성인자의 분해를 지연 시켜 작용시간을 증가 시킴으로써 과다한 혈소판활성인자의 생물학적 작용이 신증후출혈열의 병리현상을 초래할 것으로 사료된다.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Current Trends in Toxicological Sciences
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• pp.79-79
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• 2002

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants, and many of their toxic effects, including their immunotoxicities, are mediated by the activation of aryl hydrocarbon receptor (AhR). We previously reported that Aroclor 1254, one of the most widely used PCB mixtures, increased DNA fragmentation in mouse spleen cells, suggesting that apoptosis was correlated with the immunotoxicity of PCB (Yoo et al., 1997).(omitted)

• Toxicological Research
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• 제31권4호
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• pp.339-345
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• 2015

CYP1A1 is a phase I xenobiotic-metabolizing enzyme whose expression is mainly driven by AhR. Endosulfan is an organochlorine pesticide used agriculturally for a wide range of crops. In this study, we investigated the effect of endosulfan on CYP1A1 expression and regulation. Endosulfan significantly increased CYP1A1 enzyme activity as well as mRNA and protein levels. In addition, endosulfan markedly induced XRE transcriptional activity. CH-223191, an AhR antagonist, blocked the endosulfan-induced increase in CYP1A1 mRNA and protein expression. Moreover, endosulfan did not induce CYP1A1 gene expression in AhR-deficient mutant cells. Furthermore, endosulfan enhanced the phosphorylation of calcium calmodulin (CaM)-dependent protein kinase (CaMK) and protein kinase C (PKC). In conclusion, endosulfan-induced up-regulation of CYP1A1 is associated with AhR activation, which may be mediated by PKC-dependent pathways.