• 제목/요약/키워드: Promoter activation

검색결과 268건 처리시간 0.023초

20(S)- Protopanaxadiol suppresses hepatic stellate cell activation via WIF1 demethylation-mediated inactivation of the Wnt/β-catenin pathway

  • Chunxue Li ;Yating Zhan ;Rongrong Zhang;Qiqi Tao ;Zhichao Lang ;Jianjian Zheng
    • Journal of Ginseng Research
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    • 제47권4호
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    • pp.515-523
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    • 2023
  • Background: 20(S)-protopanaxadiol (PPD), one of the main components of ginseng, has anti-inflammatory, anti-estrogenic, and anti-tumor activities. It is known that activated hepatic stellate cells (HSCs) are the primary producers of extracellular matrix (ECM) in the liver, and the Wnt/β-catenin pathway participates in the activation of HSCs. We aimed to explore whether PPD inhibits liver fibrosis is associated with the Wnt/β-catenin pathway inactivation. Methods: The anti-fibrotic roles of PPD were examined both in vitro and in vivo. We also examined the levels of Wnt inhibitory factor 1 (WIF1), DNA methyltransferase 1 (DNMT1) and WIF1 methylation. Results: PPD obviously ameliorated liver fibrosis in carbon tetrachloride (CCl4)-treated mice and reduced collagen deposition. PPD also suppressed the activation and proliferation of primary HSCs. Notably, PPD inhibited the Wnt/β-catenin pathway, reduced TCF activity, and increased P-β-catenin and GSK-3β levels. Interestingly, WIF1 was found to mediate the inactivation of the Wnt/β-catenin pathway in PPD-treated HSCs. WIF1 silencing suppressed the inhibitory effects of PPD on HSC activation and also restored α-SMA and type I collagen levels. The downregulation of WIF1 expression was associated with the methylation of its promoter. PPD induced WIF1 demethylation and restored WIF1 expression. Further experiments confirmed that DNMT1 overexpression blocked the effects of PPD on WIF1 expression and demethylation and enhanced HSC activation. Conclusion: PPD up-regulates WIF1 levels and impairs Wnt/β-catenin pathway activation via the downregulation of DNMT1-mediated WIF1 methylation, leading to HSC inactivation. Therefore, PPD may be a promising therapeutic drug for patients with liver fibrosis.

The cancer/testis antigen CAGE induces MMP-2 through the activation of NF-κB and AP-1

  • Kim, Young-Mi;Jeoung, Doo-Il
    • BMB Reports
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    • 제42권11호
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    • pp.758-763
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    • 2009
  • Cancer-associated antigen (CAGE) induces the expression of matrix metalloproteinase-2 (MMP-2) by activating Akt, which in turn interacts with inhibitory kappa kinase $\beta$ ($I{\kappa}K{\beta}$) to activate nuclear factor ${\kappa}B$ (NF-${\kappa}B$). Akt and p38 mitogen activated protein kinase (p38 MAPK) are necessary for CAGE-mediated induction of the AP-1 subunit JunB, whereas extracellular regulated kinase (ERK) is necessary for the induction of fos-related antigen-1 (Fra-1). Induction of MMP-2 by CAGE requires activator of protein-1 (AP-1) to be bound. Specific binding of JunB to MMP-2 promoter sequences was shown by chromatin immunoprecipitation (ChIP) analysis.

Transcriptional activation of an anti-oxidant mouse Pon2 gene by dexamethasone

  • Lim, Ji-Ae;Kim, Sang-Hoon
    • BMB Reports
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    • 제42권7호
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    • pp.421-426
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    • 2009
  • Glucocorticoids regulate multiple physiological processes such as metabolic homeostasis and immune response. Mouse Pon2 (mPon2) acts as an antioxidant to reduce cellular oxidative stress in cells. In this present study, we investigated the transcriptional regulation of mPon2 by glucocorticoids. In the presence of glucocorticoid analogue dexamethasone, the expression of mPon2 mRNA in cells was increased, whereas the expression was inhibited by a transcription inhibitor actinomycin D. Glucocorticoid receptors bound to the putative glucocorticoid response elements located between -593 bp and -575 bp of the mPon2 promoter. Transcriptional activity was completely blocked when the putative element was mutated. Taken together, these results suggest that the expression of the mPon2 gene is directly regulated by glucocorticoid-glucocorticoid receptor complexes.

Isolation and Identification of Antitumor Promoters from the Seeds of Cassia tora

  • Park, Yeung-Beom;Kim, Seon-Bong
    • Journal of Microbiology and Biotechnology
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    • 제21권10호
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    • pp.1043-1048
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    • 2011
  • A methanol extract of Cassia tora seeds was successively partitioned with diethyl ether, chloroform, ethyl acetate, and water, and the antitumor-promoting activity of the solvent fractions was determined by inhibition of Epstein-Barr virus early antigen (EBV-EA) activation induced by teleocidin B-4 in Raji cells. The diethyl ether (68.7%) and chloroform (91.2%) fractions and the hydrolysate (94.3%) of the ethyl acetate fraction had strong inhibitory activities. The chloroform and ethyl acetate fractions were chromatographed on silica gel and further purified by HPLC. Three active compounds, obtusifolin-2-glucoside (75.0%), chryso-obtusin-6-glucoside (56.8%), and norrubrofusarin-6-glucoside (39.4%), were obtained from the ethyl acetate fraction, and two active compounds, questin (97.9%) and chryso-obtusin (53.8%), were isolated from the chloroform fraction.

허브를 이용한 일본의 지역경제활성화에 관한 연구 -일본(日本) Kawaguchikocho의 Herb Festival의 사례연구- (A study on local economy activation of Japan by herv -A case of herb festival in Kawaguchikocho Japan-)

  • 홍영록;조태동
    • 농촌계획
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    • 제5권1호
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    • pp.12-19
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    • 1999
  • This study proposes the following directions on the basis of results gained from a survey in Yamanasihyun Kawaguchikocho, where the herb festival is successfully held, in order to activate the local economy by herb. 1) The herb education for person in charge in the local authorities, the promoter of herb festival, has to be preceded and the local residents should try to understand what the herb is. 2) For a successful herb festival in the aspect of local economy and environmental conservation, detailed basic study and publicity including human -, natural environment, ecological conditions for herb should be peformed. 3) Herb event should have various programs and formats to arouse the user's interest and should be a place for environmental education.

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락토스 오페론에서 Cyclic AMP Receptor Protein에 의한 두 결합 부위(CRP1과 CRP2)의 결합 특성에 관한 연구 (The Binding Affinities of Two Binding Sites(CRP1 and CRP2 Sites) by Cyclic AMP Receptor Protein at Lactose Operon)

  • 강종백;권건
    • 생명과학회지
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    • 제13권5호
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    • pp.746-750
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    • 2003
  • Lactose operon contains two CRP binding sites at promoter(CRP1 site) and operator(CRP2 site) regions at lac operon. CRP protein can bind to both sites with the different binding affinity. CRP1 site, major CRP binding site, acts the transcription activation with the fully unknown mechanism by binding of CRP. In this study, the binding affinities of CRP1 site and CRP2 site were measured with the fluorescein-labeled oligomers, which contain CRP1 site and the three different spacing sequences between GTGA and TCAC at CRP2 site. Results showed that CRP:cAMP complex bound to CRP1 site 3 times more strongly than CRP2 site and the base spacing between GTGA and TCAC was not the only factor to affect the binding affinity of CRP to CRP2 site.

Jab1 has negative effects on p53-mediated genotoxic stresses

  • Lee, Eun-Woo;Lee, Sang-Sik;Song, Jae-Whan
    • BMB Reports
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    • 제42권5호
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    • pp.299-303
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    • 2009
  • In this study, we use promoter analysis to show that interaction between Jab1 and p53 induces suppression of p53 activation in U2OS and H1299 cells. Interaction between p53 and Jab1 was further confirmed by immunoprecipitation and immunofluorescent analyses. In particular, Jab1 was able to induce nuclear export of p53 as previously reported. When Jab1 was overexpressed in U2OS cells followed by etoposide or hydrogen peroxide ($H_2O_2$), cell death induced by such stresses was protected against. On the contrary, when the level of Jab1 was suppressed in U2OS cells, cytotoxicity imposed by etoposide and $H_2O_2$ was dramatically increased, suggesting a cell protective role for Jab1. These results indicate that Jab1 is a negative regulator of p53 and a plausible oncogene.

미분의 구형 형광체 제초에 있어서 융제의 영향 (The Effect of Flux on the Preparation of Spherical Fine Phosphor Particles)

  • 노현숙;강윤찬;서대종
    • 한국전기전자재료학회:학술대회논문집
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    • 한국전기전자재료학회 1999년도 추계학술대회 논문집
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    • pp.570-573
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    • 1999
  • High brightness (Y$_{x}$/Gd$_{1-x}$ )$_2$O$_3$:Eu Phosphor Particles were directly Prepared in the spray Pyrolysis by adding flux materials such as LiCl and HBO$_3$. The (Y$_{x}$/Gd$_{1-x}$ )$_2$O$_3$:Eu particles prepared from solution with flux material had higher PL (photoluminescence) intensities than those prepared from solution without flux. In the spray pyrolysis, the flux acts as promoter of the growth of crystallite and activation of doping material as in the solid state reaction method. Additionally, the flux improved PL intensity of (Y$_{x}$/Gd$_{1-x}$ )$_2$O$_3$:Eu phosphor particles by densifying the internal structure and eliminating the defect existing inside and surface of (Y$_{x}$/Gd$_{1-x}$ )$_2$O$_3$:Eu phosphor particles.r particles.

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MODULATION OF THE ACTIVITY OF PRO-INFLAMMATORY ENZYMES, COX-2 AND iNOS, BY CHRYSIN DERIVATIVES

  • Cho, Hee-Yeong;Yun, Cheol-Won;Kong, Jae-Yang;Kim, Kyoung-Soon;Park, You-Mie;Lee, Sang-Hyun;Kim, Bak-Kwang
    • 대한약학회:학술대회논문집
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    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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    • pp.286.1-286.1
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    • 2003
  • Chrysin, a natural flavone compound contained in plants. has anti-inflammatory activity. Its anti-inflammatory effect has been previously explained in part by the suppression of promoter activities of inducible pro-inflammatory enzymes (cyclooxygenase-2 (COX-2) and inducible nitrogen synthase (iNOS)). Nitrate production triggered by the activation of lipopolysaccharides (LPS) was most highly suppressed by the treatment of chrysin, follwed by 5-hydroxy-7-methoxyflavone (Ch-2), 5,7-diacetylflavone (Ch-4) in cultured Raw 264.7 cells. (omitted)

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

  • Cho, Il-Je;Kim, Sang-Geon
    • 대한약학회:학술대회논문집
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    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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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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