• Title/Summary/Keyword: XRE

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Effect of LG Herbal Medicine Complex (LG-HMC) on Diesel Particulate Matter (DPM) Induced Skin Inflammation and Xenobiotic Response Activity In Vitro (LG-HMC의 미세먼지 유발 염증의 완화와 생체이물대사완화 효과)

  • Shin, Jae Young;Kim, Yun Sun;Ahn, Young Je;Kang, Nae-Gyu;Lee, Sang Hwa
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.46 no.1
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    • pp.81-88
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    • 2020
  • Diesel particulate matter (DPM) induces inflammatory cytokines in HaCaT and stimulates XRE promoter activity through AhR binding. Thus, it increases CYP gene family expression. In this study, we have elucidated inhibitory effect of LG Herbal Medicine Complex (LG-HMC) on DPM-induced XRE promoter activity and inflammatory cytokine expression. First of all, the XRE promoter activity was overexpressed by DPM treatment and the LG-HMC abrogated the XRE promoter activity. Morus alba bark extract, Scutellaria baicalensis root extract and constituents of LG-HMC, were found to be main effecters against DPM induced XRE promoter activation. We also found that DPM treatment elevated inflammatory cytokines in HaCaT and the treatment of LG-HMC, Morus alba bark extract and Scutellaria baicalensis root extract down-regulated the DPM induced inflammatory cytokine expression. Additionally, Morus alba bark extract and Scutellaria baicalensis root extract were found to act as free radical scavengers. In conclusion, we confirmed skin protective effect of LG-HMC and uncovered two components, Morus alba bark extract and Scutellaria baicalensis root extract, that play major role in protecting epidermal kertinocytes from damage.

C/EBP$\beta$ mediated inhibition of PAH-inducible CYPlAl expression by Oltipraz, a cancer chemopreventive agent

  • Cho, Il-Je;Kim, Sang-Geon
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.85.3-86
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    • 2003
  • Oltipraz, a cancer chemopreventive agent, induces CYP1A1 to a certain extent by transactivation of the gene via the Ah receptor (AhR)-xenobiotic response element (XRE) pathway. Previously, we showed that oltipraz promoted CCAAT/enhancer binding protein (C/EBP ) activation, which leads to the induction of glutathione S-transferase. Given that oltipraz activates C/EBP for gene transactivation and that the putative C/CBP binding site is located in CY)1A1 promoter region, this study investigated the effect of oltipraz on CYP1A1 induction by 3-methylcholanthrene (3-MC). (omitted)

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Mechanisms of Resorcinol Antagonism of Benzo[a]pyrene-Induced Damage to Human Keratinocytes

  • Lee, Seung Eun;Kwon, Kitae;Oh, Sae Woong;Park, Se Jung;Yu, Eunbi;Kim, Hyeyoun;Yang, Seyoung;Park, Jung Yoen;Chung, Woo-Jae;Cho, Jae Youl;Lee, Jongsung
    • Biomolecules & Therapeutics
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    • v.29 no.2
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    • pp.227-233
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    • 2021
  • Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon and ubiquitous environmental toxin with known harmful effects to human health. Abnormal phenotypes of keratinocytes are closely associated with their exposure to B[a]P. Resorcinol is a component of argan oil with reported anticancer activities, but its mechanism of action and potential effect on B[a]P damage to the skin is unknown. In this study, we investigated the effects of resorcinol on B[a]P-induced abnormal keratinocyte biology and its mechanisms of action in human epidermal keratinocyte cell line HaCaT. Resorcinol suppressed aryl hydrocarbon receptor (AhR) activity as evidenced by the inhibition of B[a]P-induced xenobiotic response element (XRE)-reporter activation and cytochrome P450 1A1 (CYP1A1) expression. In addition, resorcinol attenuated B[a]P-induced nuclear translocation of AhR, and production of ROS and pro-inflammatory cytokines. We also found that resorcinol increased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activity. Antioxidant response element (ARE)-reporter activity and expression of ARE-dependent genes NAD(P)H dehydrogenase [quinone] 1 (NQO1), heme oxygenase-1 (HO-1) were increased by resorcinol. Consistently, resorcinol treatment induced nuclear localization of Nrf2 as seen by Western analysis. Knockdown of Nrf2 attenuated the resorcinol effects on ARE signaling, but knockdown of AhR did not affect resorcinol activation of Nrf2. This suggests that activation of antioxidant activity by resorcinol is not mediated by AhR. These results indicate that resorcinol is protective against effects of B[a]P exposure. The mechanism of action of resorcinol is inhibition of AhR and activation of Nrf2-mediated antioxidant signaling. Our findings suggest that resorcinol may have potential as a protective agent against B[a]P-containing pollutants.

Human CYP1A2 Promoter Fused-Luciferase Gene Constructs Hardly Respond to Polycyclic Hydrocarbons in Transient Transfection Study in HepG2 Cells

  • Chung, Injae
    • Toxicological Research
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    • v.16 no.2
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    • pp.95-100
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    • 2000
  • In previous study, both constitutive expression and 3-methylcholanthrene (3MC)-mediated elevation of CYP1A2 mRNA were demonstrated in human hepatoma HepG2 cells by reverse transcription-polymerase chain reaction (RT-PCR), suggesting that HepG2 cells would be appropriate for the study of human CYP1A2 regulation(Chung and Bresnick, 1994). Further studies were conducted to determine the basis of this induction phenomenon that is observed in HepG2 cells. Since CYP1A1 gene, another polycyclic hydrocarbon(PH)-inducible gene, is regulated by PHs through their interactions via receptors with cis-elements, the 5'-flanking region of human CYP 1A2 gene was analyzed to search such responsive elements. The promoter activity of various lengths of CYP1A2 gene sequence (-3203/+58bp) was measured in transiently-transfected HepG2 cells by fusion constructs containing the CAT, hGH or luciferase genes as a reporter. This region of the CYP1A2 gene, although containing a XRE, was only weakly responsive (less than 2 fold induction) to 10 nM of TCDD or 1 $\mu$M 3 MC treatment. This small enhancement of promoter activity is inconsistent with the previous observation, i.e., 12 to 14 fold-enhanced CYP1A2 mRNA from 1 $\mu$M 3 MC treated HepG2 cells, suggesting that additional mechanisms would exist for PH-mediated induction of CYP1A2 in these cells.

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EFFECT OF CIS-ELEMENT ON THE REGULATION Of TROUT LIVER CYTOCHROME P450IAl GENE EXPRESSION

  • Hwang, Jung E.;Sheen, Yhun Y.
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.188-188
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    • 1996
  • In order to gain insight into the mechanism of the regulation of cytochrome P450IAl by arylhydrocarbon, the 5'-flanking region of a trout CYP450IAl 5'flanking DNA was cloned into pCAT-basic vector and it was transfected into Hepa-1 cells. 3MC treatment to hepa Ⅰ cells transfected with fish CYP450IAl-CAT construct results in mRNA increased by 2.81 fold when it was compared with that of control This increase of mRNA was decreased by concomitantly treated flavonoids such as morin. The levels of CAT mRNA that was treated with morin was 29.2-58.0% of 3MC stimulated CAT mRNA. Further investigation to find out if there are DRE, XRE or negative regulatory cis element in CYP450IA1 gene was undertaken. Results of the deletion study of 5'flanking DNA of trout P450IA indicate the existance of the negative(-1600 ~ -1300). CAT mRNA was about two-fold higher in deleted trout CYP450IAl-CAT construct transfected cells compared to the wi Id type trout CYP450IAl-CAT construct transfected cells. And The stimulatory effect of 3MC was no longer observed in col Is containing deleted CAT construct. [Supported by grants from the Korean Ministry of Education]

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Endosulfan Induces CYP1A1 Expression Mediated through Aryl Hydrocarbon Receptor Signal Transduction by Protein Kinase C

  • Han, Eun Hee;Kim, Hyung Gyun;Lee, Eun Ji;Jeong, Hye Gwang
    • Toxicological Research
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    • v.31 no.4
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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.

Effects of Oxygen Partial Pressure on ITO Thin Films PrePared by Reactive dc Magenetron Sputtering (반응성 dc 미그네트론 스퍼링법으로 제조된 IPO박막에 미치는 산소분압의 영향)

  • 신성호;신재혁;박광자;김현우
    • Journal of the Korean institute of surface engineering
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    • v.31 no.3
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    • pp.171-176
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    • 1998
  • Transparent conducting ITO (Indium Tin Oxide) thin films were prepared on soda lime glass by reactive dc magnetron sputtering mothod. The maaterial properties were measured by the X-ray diffraction meter (XRD) and atomic force microscopy (AFM) scanning. As a resuIts, the (400) park for $O_2 gas rate 2% grows uniquely as the preferred orientaon. However, the (400) peak exists at $O_2 gas rate 5% as well as the (222) peak appears abruptly as the main orietation. Both <100> and <111> grain alignments are consisted simultaneously in the XRE pattern of ITO thin films. The electrical charcteristics were esimated by the electrical resistivity, optical transmission, and Hall mobillty, ect. The resistivity of ITO thin film deposited at 4cm from the substrate center is increased from $2\times10^-4$ to $8\times10^-4\Omega$cm as a function of $O_2$ gas pressure (0~5%). The optical transmission curves with a rising of $O_2$ gas rate become shifted into longer wavelength range.

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Effect of Non-indigenous Bacterial Introductions on Rhizosphere Microbial Community

  • Nogrado, Kathyleen;Ha, Gwang-Su;Yang, Hee-Jong;Lee, Ji-Hoon
    • Korean Journal of Environmental Agriculture
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    • v.40 no.3
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    • pp.194-202
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    • 2021
  • BACKGROUND: Towards achievement of sustainable agriculture, using microbial inoculants may present promising alternatives without adverse environmental effects; however, there are challenging issues that should be addressed in terms of effectiveness and ecology. Viability and stability of the bacterial inoculants would be one of the major issues in effectiveness of microbial pesticide uses, and the changes within the indigenous microbial communities by the inoculants would be an important factor influencing soil ecology. Here we investigated the stability of the introduced bacterial strains in the soils planted with barley and its effect on the diversity shifts of the rhizosphere soil bacteria. METHODS AND RESULTS: Two different types of bacterial strains of Bacillus thuringiensis and Shewanella oneidensis MR-1 were inoculated to the soils planted with barley. To monitor the stability of the inoculated bacterial strains, genes specific to the strains (XRE and mtrA) were quantified by qPCR. In addition, bacterial community analyses were performed using v3-v4 regions of 16S rRNA gene sequences from the barley rhizosphere soils, which were analyzed using Illumina MiSeq system and Mothur. Alpha- and beta-diversity analyses indicated that the inoculated rhizosphere soils were grouped apart from the uninoculated soil, and plant growth also may have affected the soil bacterial diversity. CONCLUSION: Regardless of the survival of the introduced non-native microbes, non-indigenous bacteria may influence the soil microbial community and diversity.

Purification and Characterization of Repressor of Temperate S. aureus Phage Φ11

  • Das, Malabika;Ganguly, Tridib;Chattoraj, Partho;Chanda, Palas Kumar;Bandhu, Amitava;Lee, Chia Yen;Sau, Subrata
    • BMB Reports
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    • v.40 no.5
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    • pp.740-748
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    • 2007
  • To gain insight into the structure and function of repressor proteins of bacteriophages of gram-positive bacteria, repressor of temperate Staphylococcus aureus phage ${\phi}11$ was undertaken as a model system here and purified as an N-terminal histidine-tagged variant (His-CI) by affinity chromatography. A ~19 kDa protein copurified with intact His-CI (~ 30 kDa) at low level was resulted most possibly due to partial cleavage at its Ala-Gly site. At ~10 nM and higher concentrations, His-CI forms significant amount of dimers in solution. There are two repressor binding sites in ${\phi}11$ cI-cro intergenic region and binding to two sites occurs possibly by a cooperative manner. Two sites dissected by HincII digestion were designated operators $O_L$ and $O_R$, respectively. Equilibrium binding studies indicate that His-CI binds to $O_R$ with a little more strongly than $O_L$ and binding species is probably dimeric in nature. Interestingly His-CI binding affinity reduces drastically at elevated temperatures ($32-42^{\circ}C$). Both $O_L$ and $O_R$ harbor a nearly identical inverted repeat and studies show that ${\phi}11$ repressor binds to each repeat efficiently. Additional analyses indicate that ${\phi}11$ repressor, like $\lambda$ repressor, harbors an N-terminal domain and a C-terminal domain which are separated by a hinge region. Secondary structure of ${\phi}11$ CI even nearly resembles to that of $\lambda$ phage repressor though they differ at sequence level. The putative N-terminal HTH (helix-turn-helix) motif of ${\phi}11$ repressor belongs to the HTH -XRE-family of proteins and shows significant identity to the HTH motifs of some proteins of evolutionary distant organisms but not to HTH motifs of most S. aureus phage repressors.

Effects of Formononetin on the Aryl Hydrocarbon Receptor and 7,12-Dimethylbenz[a]anthracene-induced Cytochrome P450 1A1 in MCF-7 Human Breast Carcinoma Cells

  • Han, Eun-Hee;Jeong, Tae-Cheon;Jeong, Hye-Gwang
    • Toxicological Research
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    • v.23 no.2
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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.