• 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)

• Molecules and Cells
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• 제43권11호
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• pp.935-944
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• 2020

Aryl hydrocarbon receptor nuclear translocator (ARNT) plays an essential role in maintaining cellular homeostasis in response to environmental stress. Under conditions of hypoxia or xenobiotic exposure, ARNT regulates the subset of genes involved in adaptive responses, by forming heterodimers with hypoxia-inducible transcription factors (HIF1α and HIF2α) or aryl hydrocarbon receptor (AhR). Here, we have shown that ARNT interacts with DDB1 and CUL4-associated factor 15 (DCAF15), and the aryl sulfonamides, indisulam and E7820, induce its proteasomal degradation through Cullin-RING finger ligase 4 containing DCAF15 (CRL4^DCAF15) E3 ligase. Moreover, the two known neo-substrates of aryl sulfonamide, RNA-binding motif protein 39 (RBM39) and RNA-binding motif protein 23 (RBM23), are not required for ARNT degradation. In line with this finding, aryl sulfonamides inhibited the transcriptional activities of HIFs and AhR associated with ARNT. Our results collectively support novel regulatory roles of aryl sulfonamides in both hypoxic and xenobiotic responses.

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

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.5801-5805
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• 2015

As a cytosolic transcription factor, the aryl hydrocarbon (Ah) receptor is involved in several pathophysiological events leading to immunosuppression and cancer; hence antagonists of the Ah receptor may possess chemoprevention properties. It is known to modulate carcinogen-metabolising enzymes, for instance the CYP1 family of cytochromes P450 and quinone reductase, both important in the biotransformation of many chemical carcinogens via regulating phase I and phase II enzyme systems. Utilising chemically-activated luciferase expression (CALUX) assay it was revealed that intact glucosinolates, glucoraphanin and glucoerucin, isolated from Brassica oleracea L. var. acephala sabellica and Eruca sativa ripe seeds, respectively, are such antagonists. Both glucosinolates were poor ligands for the Ah receptor; however, they effectively antagonised activation of the receptor by the avid ligand benzo[a]pyrene. Indeed, intact glucosinolate glucoraphanin was a more potent antagonist to the receptor than glucoerucin. It can be concluded that both glucosinolates effectively act as antagonists for the Ah receptor, and this may contribute to their established chemoprevention potency.

• Biomolecules & Therapeutics
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• 제14권3호
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• pp.132-136
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• 2006

Aryl hydrocarbon receptor nuclear translocator (Arnt) belongs to bHLH-PAS protein family. Here, we study the role of Arnt in both cell growth and glucose metabolism. Our results demonstrated that the absence of Arnt does affect ATP homeostasis but not cell growth in monolayer-cultured mouse hepatoma cells. ATP level of Arnt defective BpRc1 hepatoma cells is less than that of wild type hepatoma cells in both normoxia and hypoxia. BpRc1 cells also fail to increase the expression of glycolytic enzymes in response to hypoxia. Our results suggest that Arnt is essential for glucose metabolism and ATP production but not for cell growth.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2005년도 춘계 국제심포지엄 및 학술대회
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• pp.108-108
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• 2005

• Toxicological Research
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• 제23권2호
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• pp.135-142
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• 2007

Formononetin is an isoflavonoid phytoestrogen found in certain foodstuffs such as soy and red clover. In this study, we examined the action of formononetin with the carcinogen activation pathway mediated through the aryl hydrocarbon receptor (AhR) in MCF-7 breast carcinoma cells. Treating the cells with formononetin alone caused the accumulation of CYP1A1 mRNA as well as elevation in CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity in a dose dependent manner. However, a concomitant treatment with 7,12-dimethylbenz[a]anthracene (DMBA) and formononetin markedly reduced both the DMBA-inducible EROD activity and CYP1A1 mRNA level. Under the same conditions, formononetin inhibited the DMBA-induced AhR transactivation, as shown by reporter gene analysis using a xenobiotic responsive element (XRE). Additionally, formononetin inhibited both DMBA-inducible nuclear localization of the aryl hydrocarbon receptor (AhR) and metabolic activation of DMBA, as measured by the formation of the DMBA-DNA adducts. Furthermore, formononetin competed with the prototypical AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), for binding to the AhR in an isolated rat cytosol. These results suggest that formononetin might be considered as a natural ligand to bind on AhR and consequently produces a potent protective effect against DMBA-induced genotoxicity. Therefore, that's the potential to act as a chemopreventive agent that is related to its effect on AhR pathway as antagonist/agonist.

• 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.

• 한국축산식품학회지
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• 제42권6호
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• pp.1046-1060
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• 2022

This study aimed to investigate the effects of the metabolites of Latilactobacillus curvatus BYB3 and indole-activated aryl hydrocarbon receptor (AhR) to increase the tight junction (TJ) proteins in an in vitro model of intestinal inflammation. In a Western blot assay, the metabolites of L. curvatus BYB3 reduced the TJ demage in lipoploysaccharide (LPS) stimulated-Caco-2 cells. This reduction was a result of upregulating the expression of TJ-associated proteins and suppressing the nuclear factor-κB signaling. Immunofluorescence images consistently revealed that LPS disrupted and reduced the expression of TJ proteins, while the metabolites of L. curvatus BYB3 and indole reversed these alterations. The protective effects of L. curvatus BYB3 were observed on the intestinal barrier function when measuring transepithelial electrical resistance. Using high-performance liquid chromatography analysis the metabolites, the indole-3-latic acid and indole-3-acetamide concentrations were found to be 1.73±0.27 mg/L and 0.51±0.39 mg/L, respectively. These findings indicate that the metabolites of L. curvatus BYB3 have increasing mRNA expressions of cytochrome P450 1A1 (CYP1A1) and AhR, and may thus be applicable for therapy of various inflammatory gut diseases as postbiotics.

• 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)