• Title/Summary/Keyword: NR1H4

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The Role of Nuclear Receptor Subfamily 1 Group H Member 4 (NR1H4) in Colon Cancer Cell Survival through the Regulation of c-Myc Stability

  • Lee, Yun Jeong;Lee, Eun-Young;Choi, Bo Hee;Jang, Hyonchol;Myung, Jae-Kyung;You, Hye Jin
    • Molecules and Cells
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    • v.43 no.5
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    • pp.459-468
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    • 2020
  • Nuclear receptor subfamily group H member 4 (NR1H4), also known as farnesoid X receptor, has been implicated in several cellular processes in the liver and intestine. Preclinical and clinical studies have suggested a role of NR1H4 in colon cancer development; however, how NR1H4 regulates colon cancer cell growth and survival remains unclear. We generated NR1H4 knockout (KO) colon cancer cells using clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein-9 nuclease (CAS9) technology and explored the effects of NR1H4 KO in colon cancer cell proliferation, survival, and apoptosis. Interestingly, NR1H4 KO cells showed impaired cell proliferation, reduced colony formation, and increased apoptotic cell death compared to control colon cancer cells. We identified MYC as an important mediator of the signaling pathway alterations induced by NR1H4 KO. NR1H4 silencing in colon cancer cells resulted in reduced MYC protein levels, while NR1H4 activation using an NR1H4 ligand, chenodeoxycholic acid, resulted in time- and dose-dependent MYC induction. Moreover, NR1H4 KO enhanced the anti-cancer effects of doxorubicin and cisplatin, supporting the role of MYC in the enhanced apoptosis observed in NR1H4 KO cells. Taken together, our findings suggest that modulating NR1H4 activity in colon cancer cells might be a promising alternative approach to treat cancer using MYC-targeting agents.

Identification and characteristics of Lactic Acid Bacteria Isolated from Nuruk (누룩으로부터 젖산세균의 분리 및 특성)

  • 이정훈
    • KSBB Journal
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    • v.15 no.4
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    • pp.359-365
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    • 2000
  • Three lactic acid bacteria (C-1 K-3 and T-1 strain) were isolated from Nuruk and characterized subsequently. They were useful strains for production of lactic acid and their growth was inhibited at 10% ethanol pH 4 These strains were identified as lactococcus lactis subsp. lactis NR C-1 Leuconostoc mesenteroides subsp. mesenterides NR K-3 and pediococcus pentosaceus NR T-1 respectively by morphological physiological and biochemical characterization Lac lactis subsp lactis NR C-1 showed the highest lactic acid productivity. Leu measenteroides subsp mesenteroides NR K-3 showed stable lactic acid productivity and its growth was inhibited at pH 4. P pentosaceus NR T-1 had lower lactic acid productivity than the other two bacteria but it could not grow at 10% ethanol pH 4 The lactic acid productivity of these three strains in MRS broth were higher than that in Skim milk media the optimum pH and temperature for the lactic acid production of the three strains were 30-32$^{\circ}C$ and pH 6.0∼6.8 Glucose was the optimal carbon souorce for the lactic acid production. In terms of antagonism lac lactis subsp lactis NR c-1 showed somewhat inhibitory efects against some Gram positive rod and cocci such as Lactobacillus brevis and Streptococcus mitis. And Leu mesenteroides subsp mesenteroides NR K-3 showed the inhibitory effects against Streptococcus mitis but P. pentosaceus NR T-1 didn't show any inhibitory effects against tested strains.

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T0901317 as an Inhibitor of Transcriptional Activation of Constitutive Androstane Receptor (CAR) (Constitutive androstane receptor (CAR)의 전사활성 저해제로서의 T0901317)

  • Kim, Hyun-Ha;Seol, Won-Gi
    • Journal of Life Science
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    • v.21 no.4
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    • pp.481-485
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    • 2011
  • T0901317 is a potent synthetic ligand for liver X receptor (LXR, NR1H2/3), a member of the nuclear receptor superfamily that functions as a transcription factor. However, T0901317 has been also reported to modulate the activity at least four other nuclear receptors (NRs), acting as agonists for farnesoid X receptor (FXR, NR1H4) and pregnane X receptor (PXR, NR1I2) and as antagonists for androgen receptor (AR, NR3C4) and retinoid-related orphan receptor-${\alpha}$ (ROR-${\alpha}$, NR1F1). We report here that T0901317 can also function as an inhibitor for constitutive androstane receptor (CAR, NR1I3). Since CAR is a major player of xenobiotic and cholesterol metabolism in the liver, along with PXR, FXR and LXR, which are reported to be regulated by T0901317, this further complicates the interpretation of potential results with T0901317 in liver cells.

Metal Complexes of Ambidentate Ligand (VIII). Ni (II) and Pd (II) Complexes of Isonitrosomethylacetoacetate Imines (Ambidentate 리간드의 금속착물 (제 8 보). Isonitrosomethylacetoacetate Imine 리간드의 니켈(II) 및 팔라듐(II) 착물)

  • Bon-Chang Goo;Gang-Yeol Choi;Man-Ho Lee;In-Whan Kim
    • Journal of the Korean Chemical Society
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    • v.37 no.7
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    • pp.662-671
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    • 1993
  • New Ni(II) and Pd(II) complexes of isonitrosomethylacetoacetate imine derivatives, Ni(IMAA-NH)(IMAA-NH'), Ni(IMAA-NH)(IMAA-NR), $Pd(IMAA-NH)_2\;and Pd(IMAA-NR)_2(R=CH_3,\;C_2H_5,\;n-C_3H_7,\;n-C_4H_9,\;or\;CH_2C_6H_5)$, where H-IMAA-NH and H-IMAA-NR represent isonitrosomethylacetoacetate imine and N-alkylisonitrosomethylacetoacetate imine derivative, respectively, have been prepared and the structures of the complexes have been studied by elemental analyses, electronic, infrared, and $^1H-\;and\;^{13}C-NMR$ spectroscopies.

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Formulation and Quality Characteristics of Noni Beverages Mixed with Red Ginseng, Rubus Coreanus and Pomegranate Extracts (홍삼, 복분자, 석류를 첨가한 노니 혼합음료의 개발과 품질특성)

  • Kim, Eun-Mi
    • Culinary science and hospitality research
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    • v.17 no.1
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    • pp.259-269
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    • 2011
  • The purpose of this study was to investigate the physicochemical and sensory characteristics of Noni beverages added with 10% of water(Noni 90), 1% of red ginseng(NR), 4% of rubus coreanus extract(NR), 5% of pomegranate extract(NP), and 4% of rubus coreanus extract and 5% of pomegranate extract(NPR). Calories, protein and total fiber contents were increased in NR, NP and NPR. Total sugar was significantly increased in NG and NPR. Fat, cholesterol and saturated fatty acid were not detected. Ca and Na contents were increased in NG while Fe content was increased in NG, NR, and NPR pH was significantly increased in NG and NP. Sugar degree was significantly increased in NP and NPR. L and b values were decreased in NG, NP, and NR and a value was increased in NG and NR General bacteria count was 0/mL, and Coliform, E. Coli and 0157:H7 were gram(-) in all beverages. In sensory evaluation, color was increased in NPR while taste and overall quality were increased in NG, NR and NP. Sour taste, sweet taste, and flavor were not different between Noni and the mixed beverages. Texture was significantly increased in NP and NPR. Therefore, mixed Noni beverages added with red ginseng, rubus coreanus extract, and pomegranate extract were better than Noni beverage.

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A Study on the Elution Behavior of Pd-Isonitroso ethylacetoacetate imine Chelates by Reversed-phase High Performance Liquid Chromatography (역상 고성능 액체 크로마토 그래피에 의한 Pd(II) - isonitrosoethylacetoacetate imine 유도체 킬레이트의 용리거동에 관한 연구)

  • Kim, Hyun
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.19 no.1
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    • pp.20-30
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    • 1993
  • Liquid Chromatographic behavior of Pd(II) in Isonitosoethylacetoacetate imine IEAA-NR: R=H, CH3, C2H5, n-C3H7, n-C4H9, C6H5-CH2) Chelates were investigated by reversed phase high performance 1iquid chromatography on Micropak MCH-5 Column using Methanol /water as mobile phase. The optimum condition for the separation of Pd-Isonitrosoethylacetoacetate imine chelates were examined with respect to the flow rate, mobile phase strength. It was found that Pd(IEAA-NR)2 chelates were eluted in an acceptable range of the capacity factor value (0 $\leq$ log k' $\leq$ 1), The dependence of the logarithm of capacity factor(k') on the volume fraction of water in mixture with in the binary mobile phase was examined. Also, the dependence of k'on the liquid-liquid extraction distribution constant in methanol-water / n-alkane extraction system was on system was invert tigated for Pd(IEAA-NR)2. Both kinds of dependence are linear, which suggests that the retention of the electroneutral metal chelates be largely due to the solvophobic effect.

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Effects of Nrogen Form and Light Conditions on the Nitrate Reductase Activity of Ulva pertusa (Chlorophyta) and Ecklonia cava (Phaeophyta) (구멍갈파래 (Ulva pertusa Kjellman)와 감태 (Ecklonia cava Kjellman)의 질산환원요소 활성에 미치는 질소원 형태와 빛의 효과)

  • Hwang, Jae-Ran;Kang, Yun-Hee;Oak, Jung-Hyun;Lee, Sang-Rae;Chung, Ik-Kyo
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.44 no.1
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    • pp.64-70
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    • 2011
  • Nitrate reductase (NR) is activated by nitrogen sources (${NO_3}^-$ and ${NH_4}^+$) and irradiance. This study investigated the effects of these factors on the NR activity of Ulva pertusa (Chlorophyta) and Ecklonia cava (Phaeophyta). In addition, the ammonium (${NH_4}^+$) and nitrate (${NO_3}^-$) uptake rates of the two species were examined. U. pertusa took up most of the ${NO_3}^-$ and ${NH_4}^+$ in the medium during a 3hour incubation, while E. cava had a relatively high uptake rate after 3 hours. The NR activities of the two species were affected by the nitrogen source and irradiance and were highest when they were exposed to ${NO_3}^-$-rich medium and high irradiance. However, the patterns of NR activity differed between the two species. In ${NO_3}^-$-rich medium and high irradiance, U. pertusa achieved the highest NR activity ($2.01{\pm}0.07\;{\mu}mol$ ${NO_2}^-$ $g^{-1}$ DW $h^{-1}$) within the first 3 hours and then this activity decreased drastically. By contrast, the NR activity of E. cava ($0.36{\pm}0.04\;{\mu}mol$ ${NO_2}^-$ $g^{-1}$ DW $h^{-1}$) was constant for 12 hours. When exposed to darkness, the NR activity of U. pertusa decreased dramatically, while that of E. cava increased gradually for 12 hours. Therefore, E. cava is able to maintain NR activity during the dark because of its adequate carbohydrate reserves and substrate.

Metal Complexes of Ambidentate Ligand (VI). Palladium(II) Complexes of Isonitrosoethylacetoacetate Imines (Ambidentate 리간드의 금속착물 (제 6 보). Isonitrosoethylacetoacetate Imine 리간드의 팔라듐 (II) 착물)

  • Jun Young-Sook;Lee Man-Ho;Kim In-Whan;Kim Soo-Han
    • Journal of the Korean Chemical Society
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    • v.35 no.4
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    • pp.368-373
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    • 1991
  • Palladium(II) complexes of the type Pd(IEAA-NR)$_2$ (R = H, CH$_3$, C$_2$H$_5$, n-C$_3$H$_7$, n-C$_4$H$_9$, or CH$_2$C$_6$H$_5$), where IEAA-NR represents N-alkyl derivative of isonitrosoethylacetoacetate (H-IEAA) imine, have been prepared. And the structure of the complexes have been studied by elemental analyses, electronic, infrared, $^1$H and $^{13}$C-NMR spectra. It is proposed that both of IEAA-NR ligands coordinate to metal through nitrogens of imine and isonitroso groups to form 5-membered chelate rings in the complexes.

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Characteristics of a-Amylase of, a New Species, Aspergillus coreanus NR 15-1 (시종 누룩사상균, Aspergillus coreanus NR 15-1의 a-Amylase의 효소학적 특성)

  • 이상훈;정혁준;여수환;김현수;유대식
    • KSBB Journal
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    • v.19 no.4
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    • pp.301-307
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    • 2004
  • The characteristics of the a-amylase of Aspergillus coreanus NR 15-1 isolated from traditional Korean Nuruk have been carried out. The a-amylase of A. coreanus NR 15-1 was purified by ammonium sulfate precipitation followed by column chromatographies on CM-cellulose, DEAE-cellulose, Sephadex G-100 gel filtration and hydroxyapatite. The a-amylase was purified 78-fold with a yield of 8.7%. The molecular weight of the a-amylase was estimated to be 49 kDa by Sephadex G-100 gel filtration and 51 kDa by SDS-polyacrylamide gel eletrophoresis. These experimental results suggested that the purified enzyme might be monomer. The enzyme was stable between pH 4 and 11. The optimum pH was 5.0. The optimum temperature for enzyme was 45$^{\circ}C$ and the enzyme was stable up to 50$^{\circ}C$. The enzyme was significantly inhibited by 1 mM N-bromosuccinimide. These results suggested that tryptophan residue was involved in the active site of a-amylase. The enzyme was identified as a-amylase because the reaction products of soluble starch hydrolyzed by the purified enzyme was oligosaccharide by thin layer chromatography.

Optimal Conditions of Protoplast Formation of Aspergillus coreanus NR 15-1 and Aspergilus oryzae NR 2-5 (Aspergillus coreanus NR 15-1 과 Aspergillus oryzae NR 2-5의 원형질체 형성의 최적조건)

  • 정혁준;유대식
    • Microbiology and Biotechnology Letters
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    • v.29 no.1
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    • pp.12-17
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    • 2001
  • Aspergil-lus coreanus NR-15 and Aspergilus oryzae NR-2-5 from traditional Korean Nuruk were selected as parental strains producing starch hydrolysis enzyme. Xll(Arginine-) mutant from A. coreanus NR 15-1 showed high glu-doamylase activity and total acid productivity. Z6(Adenine-) mutant from A. oryzae NR2-5 showed the highest $\alpha$-amylase activity. Therefore, both XII and Z6 mutants were selected and investigated for the optimal conditions of protoplast formation for protoplast fusion. Mixture of equal amount of cellulase and driselase(10mg/ml each) was the most effective as lytic enzymes. The optimal pH and temperature for protoplast formation were 5.0 and $30^{\circ}C$, respectively. The most effective reaction for protoplast formation time was 4 hours. The maximum of protoplst for- mation of Xll mutant and Z6 mutant were $6.54$\times$10^{7}$ protoplasts/ ml and $3.04$\times$10^{ 7}$ protoplasts/ml, and the regen-eration frequencies of the protoplasts were 11.3% and 11.6%, respectively. The size of the protoplasts from X11 and Z6 mutants were 3~6 $\mu\textrm{m}$ and 4~9$\mu\textrm{m}$, respectively.

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