• 제목/요약/키워드: MG-132

검색결과 416건 처리시간 0.023초

Inhibition of Wnt Signaling by Silymarin in Human Colorectal Cancer Cells

  • Eo, Hyun Ji;Park, Gwang Hun;Jeong, Jin Boo
    • Biomolecules & Therapeutics
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    • 제24권4호
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    • pp.380-386
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    • 2016
  • Silymarin from milk thistle (Silybum marianum) has been reported to show an anti-cancer activity. In previous study, we reported that silymarin induces cyclin D1 proteasomal degradation through NF-${\kappa}B$-mediated threonine-286 phosphorylation. However, mechanism for the inhibition of Wnt signaling by silymarin still remains unanswered. Thus, we investigated whether silymarin affects Wnt signaling in human colorectal cancer cells to elucidate the additional anti-cancer mechanism of silymarin. Transient transfection with a TOP and FOP FLASH luciferase construct indicated that silymarin suppressed the transcriptional activity of ${\beta}$-catenin/TCF. Silymarin treatment resulted in a decrease of intracellular ${\beta}$-catenin protein but not mRNA. The inhibition of proteasome by MG132 and $GSK3{\beta}$ inhibition by SB216763 blocked silymarin-mediated downregulation of ${\beta}$-catenin. In addition, silymarin increased phosphorylation of ${\beta}$-catenin and a point mutation of S33Y attenuated silymarin-mediated ${\beta}$-catenin downregulation. In addition, silymarin decreased TCF4 and increased Axin expression in both protein and mRNA level. From these results, we suggest that silymarin-mediated downregulation of ${\beta}$-catenin and TCF4 may result in the inhibition of Wnt signaling in human colorectal cancer cells.

Removal of Cd(II) and Cu(II) from Aqueous Solution by Agro Biomass: Equilibrium, Kinetic and Thermodynamic Studies

  • Reddy, Desireddy Harikishore Kumar;Lee, Seung-Mok;Seshaiah, Kalluru
    • Environmental Engineering Research
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    • 제17권3호
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    • pp.125-132
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    • 2012
  • The removal of Cd(II) and Cu(II) from aqueous solution by an agricultural solid waste biomass prepared from Moringa oleifera bark (MOB) was investigated. The biosorbent was characterized by Fourier transform infrared spectroscopy and elemental analysis. Furthermore, the effect of initial pH, contact time, biosorbent dosage, initial metal ion concentration and temperature on the biosorption of Cd(II) and Cu(II) were studied using the batch sorption technique. Kinetic studies indicated that the biosorption process of the metal ions followed the pseudo-second order model. The biosorption data was analyzed by the Langmuir, Freundlich, Dubinin-Radushkevich, and Temkin isotherm models. Based on the Langmuir isotherm, the maximum biosorption capacities for Cd(II) and Cu(II) onto MOB were 39.41 and 36.59 mg/g at 323 K, respectively. The thermodynamic parameters, Gibbs free energy (${\Delta}G^o$), enthalpy (${\Delta}H^o$), and entropy (${\Delta}S^o$) changes, were also calculated, and the values indicated that the biosorption process was endothermic, spontaneous and feasible in the temperature range of 303-323 K. It was concluded that MOB powder can be used as an effective, low cost, and environmentally friendly biosorbent for the removal of Cd(II) and Cu(II) ions from aqueous solution.

Neuroprotective Effect of Wogonin: Potential Roles of Inflammatory Cytokines

  • Piao, Hua-Zi;Jin, Shun-Ai;Chun, Hyang-Sook;Lee, Jae-Chul;Kim, Won-Ki
    • Archives of Pharmacal Research
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    • 제27권9호
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    • pp.930-936
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    • 2004
  • Wogonin (5,7-dihydroxy-8-methoxyflavone), an active component originated from the root of Scutellaria baicalensis Georgi, has been reported to possess antioxidant and anti-inflamma-tory properties. In this study, we investigated the neuroprotective effect of wogonin in a focal cerebral ischemia rat model. Wogonin markedly reduced the infarct volume after 2 h middle cerebral artery occlusion followed by 22 h reperfusion. Wogonin decreased the production of nitric oxide and inflammatory cytokines such as TNF-$\alpha$ and IL-6 in lipopolisaccharide-stimu-lated microglial cells. While wogonin reduced the activity of NF-$textsc{k}$B, it did not change the activ-ity of mitogen-activated protein kinases family members, p38, ERK and JNK. The lipopolisaccharide-stimulated production of NO and cytokines was significantly blocked by vari-ous kinds of NF-$textsc{k}$B inhibitors such as N-acetyl cysteine, pyrrolidinedithiocarbamate and MG-132. The data may indicate that wogonin has neuroprotective effect by preventing the over-activation of microglial cells, possibly by inactivating NF-$textsc{k}$B signaling pathway

단일액상원료를 사용하는 MOCVD법에 의한 YBa$_2Cu_3O_x$ 박막 제조에 관한 연구 (Preparation of YBa$_2Cu_#O_x$ films by MOCVD using single liquid solution source)

  • 김보련;이희균;홍계원;지영아;신형식
    • 한국초전도학회:학술대회논문집
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    • 한국초전도학회 1999년도 High Temperature Superconductivity Vol.IX
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    • pp.129-132
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    • 1999
  • A new single solution source MOCVD technique for the deposition of YBCO film has been developed, using a ultrasonic atomizer to feed the precursors into an evaporation zone. This method being investigated as a basis for future long wire fabrication, for example the electric power use, the magnatic applications, etc.. YBCO films were prepared on MgO(100) substrate, using mixture of Y, Ba, and Cu ${\beta}$ -diketonate chelate was dissolve in tetrahydrofuran as a solution sources. X-ray diffraction measurement indicated that the thin film grew epitaxially with the c-axis orientation perpandicular to the surface of the surface.

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Loss of estrogen responsiveness under hypoxia occurs through hypoxia inducible factor-l induced proteasome-dependent down regulation of estrogen receptor

  • Cho, Jung-Yoon;Kim, Duk-Kyung;Lee, Young-Joo
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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    • pp.70-70
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    • 2003
  • Estrogen receptor is a ligand-activated transcription factor. Its action depends on the receptor, its ligand, and its coactivator proteins. As a consequence, the concentration of the receptor is a major component that governs the magnitude of the estrogen response. Despite the extensive knowledge on mechanism of estrogen receptor action, regulation of estrogen receptor itself is not very well understood. Estrogen receptor is known to be downregulated under hypoxia leading to inhibition of estrogen receptor mediated transcription activation. We have studied mechanism of loss of estrogen responsiveness under hypoxia. We found that Hif-l${\alpha}$, a major transcription factor regulating hypoxic response, inhibited transcription of estrogen response element driven luciferase gene by expression of HIF-l${\alpha}$/vp16 construct designed to contain transcription activity under normoxia. This loss of estrogen responsiveness appears to be the result of ER${\alpha}$ downregulation. ER${\alpha}$was downregulated at the levels of ligand-biding and protein within l2-24h, and the response was blocked by the proteasome inhibitor MG132, protein synthesis inhibitor cyclohexamide, and tyrosine kinase inhibitor Genistein. These results demonstrate that Hif-l${\alpha}$ downregulates ER${\alpha}$ by proteasome dependent pathway.

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Development of an in Vitro Assay for the Proteolytic Processing of the CDP/Cux Transcription Factor

  • Hebert, Sherry;Berube, Ginette;Nepveu, Alain
    • BMB Reports
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    • 제36권4호
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    • pp.390-398
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    • 2003
  • The CDP/Cux transcription factor was previously shown to be proteolytically processed at the G1/S transition. In view of characterizing and eventually identifying the protease responsible for CDP/Cux processing, we have established an in vitro proteolytic processing assay. CDP/Cux recombinant proteins expressed in mammalian or bacterial cells were efficiently processed in vitro using as a source of protease either whole cell extracts, the nuclear or the cytoplasmic fraction. Processing was found to take place optimally at a lower pH, to be insensitive to variations in salt concentration, and to be inhibited by the protease inhibitors MG132 and E64D. Interestingly, the bacterially-produced substrate was more efficiently processed than the substrate purified from mammalian cells. Moreover, processing in vitro was more efficient when CDP/Cux substrates were purified from populations of cells enriched in the S phase than in the G1 phase of the cell cycle. Altogether, these results suggest that post-translational modifications of CDP/Cux in mammalian cells inhibits processing and contributes to the cell cycle-dependent regulation of processing. The in vitro processing assay described in this study will provide a useful tool for the purification and identification of the protease responsible for the processing of CDP/Cux.

Characteristics of Pollutant Loads and Water Quality in Kwangyang Bay, Korea

  • Lee Dae-In;Park Chung-Kil;Cho Hyeon-Seo
    • Fisheries and Aquatic Sciences
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    • 제6권3호
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    • pp.149-154
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    • 2003
  • The characteristics of pollutant loads from the various sources and seawater quality in Kwangyang Bay were evaluated. Total flow rate was estimated to be $10,868,066.8 m^3/day$ with a flow rate of R2l (the Seomjin River) as the highest one. Total COD, TN and TP loads of the input rivers and the ditches were about 27,591.8, 25,029.6 and 586.4 kg/day, respectively. Wastewater discharging loads was the greatest contributors to pollutant loads in the inner part of Kwangyang Bay. COD values in the inner part of the bay was over 3.0 mg/L, which exceeded the seawater quality criteria III of Korea. The average values of DIN and DIP were 8.62 ${\mu}gN/L\;and\;1.26\;{\mu}gP/L$, respectively. The limiting factor for algal growth was DIN. In he total discharging loads of the watershed from unit loading estimations, BOD, TN and TP were 9,132.3, 2,727.2 and 304.2 kg/day, respectively. In addition, municipal sewage by the population as pollution sources and the city of Kwangyang as administrative district had the highest loads. For a appropriate water quality recovery of Kwangyang Bay, it is suggested that it is essential to estimate reduction rate of total pollutant loads by water quality modeling.

Anti-inflammatory Activities of Undaria pinnatifida and Laminaria japonica (Phaeophyta)

  • Cho, Ji-Young;Kang, Ji-Young;Khan, Mohammed Nurul Absar;Park, Nam-Hee;Kim, Sang-Kwon;Hong, Yong-Ki
    • Fisheries and Aquatic Sciences
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    • 제10권3호
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    • pp.127-132
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    • 2007
  • The anti-inflammatory activities of dichloromethane, ethanol, and boiling water extracts of the brown seaweeds Undaria pinnatifida (Harvey) Suringar and Laminaria japonica Areschoug were examined. Ethanol extracts (0.4 mg/ear) of U. pinnatifida inhibited inflammatory symptoms in mouse ear edema by 95.3%, and dichloromethane extract inhibited erythema by 65.5%. Dichloromethane and ethanol extracts (4 g/kg bw) of L. japonica demonstrated potent antipyretic activity. Activities of the seaweed extracts were similar to those of the commonly used drugs indomethacin and acetyl salicylic acid. No acute toxicity was observed after p.o. administration of each extract (5 g/kg bw). These results were in agreement with the claims of the health care industry and indigenous medicine that the above seaweeds can be used as an effective remedy for inflammation-related symptoms.

A Transfer of Silver Nanoparticles from Pregnant Rat to Offspring

  • Lee, Yeon-Jin;Choi, Jong-Hye;Kim, Pil-Je;Choi, Kyung-Hee;Kim, Su-Hyon;Shon, Woo-Chan;Park, Kwang-Sik
    • Toxicological Research
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    • 제28권3호
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    • pp.139-141
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    • 2012
  • Silver nanoparticles (size: $7.9{\pm}0.95$ nm, dosage: 250 mg/kg) were orally administered to pregnant rats. At 4 days after parturition, four pups were randomly selected (one pup from one dam) and silver level in liver, kidney, lung and brain was determined by ICP-MS and electron microscope. As results, silver nanoparticles highly accumulated in the tissues of the pups. Silver level in the treated group was $132.4{\pm}43.9$ ng/g in the kidney (12.3 fold compared to control group), $37.3{\pm}11.3$ ng/g in the liver (7.9 fold), $42.0{\pm}8.6$ ng/g in the lung (5.9 fold), and $31.1{\pm}4.3$ ng/g in the brain (5.4 fold). This result suggested that the possible transfer of silver nanoparticles from pregnant dams to the fetus through mainly placenta.

Tamoxifen Suppresses Clusterin Level through Akt Inactivation and Proteasome Degradation in Human Prostate Cancer Cells

  • Shim, Jae-Ho;Choi, Chang-Su;Lee, Eun-Chang;Kim, Mie-Young;Chun, Young-Jin
    • Biomolecules & Therapeutics
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    • 제17권1호
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    • pp.25-31
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    • 2009
  • Clusterin is a heterodimeric sulfated glycoprotein and plays a role in many different types of cancer as a cell survival factor and helps cancerous cells to evade stress-induced apoptosis. To investigate whether the regulation of clusterin expression is involved in the mechanism of anticancer agent, we studied the effect of tamoxifen on clusterin expression in human prostate cancer PC-3 cells. Treatment of PC-3 cells with tamoxifen reduced cellular proliferation. Western blot analyses showed that treatment with tamoxifen suppressed clusterin expression in a concentration-dependent manner. Transfection with clusterin siRNA plasmid showed that clusterin is required for PC-3 cell survival. We found that tamoxifen resulted in a rapid decrease in the phosphorylation of Akt on Ser473 leading to prevent kinase activity. Expression of myristoylated Akt prevented tamoxifen-mediated clusterin downregulation. Interestingly, MG132, a wellknown proteasome inhibitor also recovered clusterin expression suppressed by tamoxifen. These data indicate that clusterin expression may be regulated by activation of Akt and ubiquitin-proteasome pathway plays an important role in tamoxifen-mediated clusterin suppression.