• Title/Summary/Keyword: inhibitor-1

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SIRT1 Inhibitor Enhances Hsp90 Inhibitor-mediated Abrogation of Hsp90 Chaperone Function and Potentiates the Cytotoxicity of Hsp90 Inhibitor in Chemo-resistant Human Cancer Cells (SIRT1 inhibitor에 의한 Hsp90 inhibitor의 Hsp90 샤페론 기능 억제 및 항암제 내성세포의 Hsp90 inhibitor에 대한 세포독성 증강)

  • Moon, Hyun-Jung;Lee, Su-Hoon;Kim, Hak-Bong;Lee, Kyoung-A;Kang, Chi-Dug;Kim, Sun-Hee
    • Journal of Life Science
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    • v.26 no.7
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    • pp.826-834
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    • 2016
  • The present investigation was undertaken to examine the effectiveness of the combination treatment of an Hsp90 inhibitor and a SIRT1 inhibitor on suppressing the growth of chemo-resistant human cancer cells. We showed that inhibition of SIRT1 effectively potentiated the cytotoxicity of 17-allylamino-17-demethoxygeldanamycin (17-AAG) and reversed Hsp90 inhibitor resistance in multidrug-resistant (MDR) human ovarian HeyA8-MDR cells. Amurensin G, a potent natural SIRT1 inhibitor, enhanced Hsp90 inhibitor-mediated abrogation of the Hsp90 chaperone function and accelerated degradation of mutated p53 (mut p53), an Hsp90 client protein, by up-regulation of ubiquitin ligase CHIP. Knock-down of CHIP significantly attenuated amurensin G-induced mut p53 degradation. Down-regulation of mut p53 reduced the expression of heat shock factor1 (HSF1)/heat shock proteins (Hsps), a major cause of Hsp90 inhibitor resistance, which led to sensitization of the MDR cells to the Hsp90 inhibitor by the SIRT1 inhibitor. Amurensin G potentiated cytotoxicity of the Hsp90 inhibitor in HeyA8-MDR cells through suppression of 17-AAG-induced Hsp70 and Hsp27 induction via down-regulation of mut p53/HSF1, and it caused activation of PARP and inhibition of Bcl-2. Our data suggests that SIRT1 inhibitors could be used to sensitize MDR cells to Hsp90 inhibitors, possibly through suppression of the mut p53/HSF1-dependent pathway, and a novel mut p53-directed action of SIRT1 inhibition could effectively prevent mut p53 accumulation in MDR cells.

Isolation and Cultivation of Microorganism Producing Lipoxygenase Inhibitor (Lipoxygenase Inhibitor를 생산하는 미생물의 분리 및 배양)

  • 황지숙;정영기이태호
    • KSBB Journal
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    • v.8 no.4
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    • pp.375-381
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    • 1993
  • The microorganisms producing a lipoxygenase inhibitor were screened from a wide variety of sources. The isolated strain was assigned to genus Penicillium by its cultural and morphological characteristics. The proper medium for the production of lipoxygenase inhibitor was composed of glucose 3.0%, ammonium sulfate 0.4%, and potassium phosphate (dibasic) 0.1%. The cultivation for lipoxygenase inhibitor production was carried out in 500m1 Erlenmyer flasks containing 100m1 of the medium at $30^{\circ}C$ by cultivating reciprocally. The highest lipoxygenase inhibitor production was observed after 8 days of cultivation. The inhibitor was the low molecular weight substance and inhibited specifically soybean origin lipoxygenase.

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Effect of Mitochondrial Inhibitor on Lactate Dehydrogenase of Mesocricetus auratus and Bos taurus coreanae (햄스터와 소의 젖산탈수소효소에 대한 미토콘드리아 inhibitor의 영향)

  • Cho Sung Kyu;Lee Sang Hak;Yum Jung Joo
    • Journal of Life Science
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    • v.15 no.1 s.68
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    • pp.100-105
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    • 2005
  • The lactate dehydrogenase (EC 1.1.1.27, LDH) inhibitors were isolated from the LDH-free crude mitochondrial fraction of skeletal muscle in Syrian hamster (Mesocricetus auratus) and Korean native cattle (Bos taurus coreanae). The LDH inhibitor in skeletal muscle of M. auratus was successfully isolated by the treatment with 175 mM NaCl and ultrasonic. The LDH inhibitor in skeletal muscle of B. taurus coreanae was highly stable to heat and LDH fu isozyme was largely inhibited by the LDH inhibitor. The molecular weight of inhibitor was 22 kDa. Inhibitor played an important role in the binding of LDH with the mitochondria in tissues of skeletal muscle, kidney and liver except heart.

The Effect of Corrosion Inhibitor on Corrosion Control of Copper Pipe and Green Water Problem

  • Lee, Ji-Eun;Lee, Hyun-Dong;Kim, Gi-Eun
    • Environmental Engineering Research
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    • v.17 no.1
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    • pp.17-25
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    • 2012
  • Concern about green water problem has surfaced as a serious issue in Korea. In order to solve this problem, it is necessary to research inhibition of green water and corrosion control of copper pipe in water service. This paper discovered that moderate corrosion inhibitors can solve the green water problem and copper corrosion in water service by adding the optimal concentration of corrosion inhibitors based on regulation. Firstly, in the case of phosphate based corrosion inhibitors, as dosage of the corrosion inhibitor increases from 1 mg/L to 5 mg/L, the relative effect of corrosion inhibitor declines rapidly. Secondly, except for 1 mg/L dosage of silicate based inhibitor, relative effects of the inhibitor displays a positive number depending on inhibitor concentration. The most significant result is that the amount of copper release shows a downward trend, whereas the phosphate based inhibitor accelerates copper ion release as the inhibitor dosage increases. Thirdly, as the dosage of mixed inhibitors increases to 10 mg/L, the copper release change shows a similar trend of phosphate based inhibitor. Lastly, according to the Langelier saturation index (LI), silicate based inhibitors have the most non corrosive value. Larson ratio (LR) indicates that phosphate based inhibitors are the least corrosive. Korea water index (KWI) represents that silicate based inhibitors are most effective in controlling copper pipe corrosion.

Characteristics of the Protease Inhibitor Purified from Chum Salmon (Oncorhynchus keta) Eggs

  • Kim, Kenn-Yeong;Ustadi, Ustadi;Kim, Sang-Moo
    • Food Science and Biotechnology
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    • v.15 no.1
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    • pp.28-32
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    • 2006
  • Protease inhibitor of 72.6 kDa was successively purified from chum salmon (Oncorhynchus keta) eggs by ion exchange, gel permeation, and affinity chromatographies. Protease inhibitor was purified with yield and purification fold of 1.50% and 58.11, respectively. SDS-PAGE results showed purified protease inhibitor consisted of two protein subunits of 54.0 and 18.6 kDa. Chum salmon inhibitor exhibited stability between 20 and $40^{\circ}C$ in weak acid environment (PH 6), and inhibited papain and cathepsin, members of cysteine protease, but not chymotrypsin. The protein inhibited cathepsin more effectively than did egg white protease inhibitor, whereas the reverse was true for papain. These results indicate chum salmon egg inhibitor is heterodimer, thus the inhibitor was classified as cysteine protease inhibitor.

Coating formation of water supply pipes by inhibitor and water quality improvement effect (부식억제제에 의한 상수도관의 피막 형성 및 수질개선 효과)

  • Lim, Jae-Cheol;Kim, Jin-Keun;Koo, Ja-Yong
    • Journal of Korean Society of Water and Wastewater
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    • v.26 no.1
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    • pp.97-106
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    • 2012
  • To investigate the application of corrosion inhibitor on water supply pipes, turbidity, magnitude of corrosion, composition of scale and concentration of metals from an old steel pipe were analysed under inhibitor addition. The concentration of turbidity, iron and copper from the pipes under inhibitor application was 12 ~ 14% of the case which no inhibitor was applied, which suggests the application of inhibitor was very effective for internal corrosion control. In addition, SEM, EDX, XRD and XRF test results showed that application of inhibitor was effective for the decrease of iron concentration and increase of oxygen, phosphorus and calcium concentration, which suggested the existence of protective layer. Therefore, the occurrence of red water will be significantly decreased when inhibitor was applied to the old steel pipes.

Bowman-Birk type proteinase inhibitors from soybean : Isolation and partial characterization (대두 Bowman-Birk형 proteinase inhibitor들의 분리 및 성질)

  • Choi, Ki-Bong;Kim, Su-Il
    • Applied Biological Chemistry
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    • v.33 no.4
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    • pp.287-292
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    • 1990
  • Eight(I through VII) of Bowman-Birk proteinase inhibitor have been isolated from soybean with DEAE-Sephadex A-50. Inhibitor VII was a typical BBTI, showing high cysteine content(17%/mole) ud low trypsin to chymotrypsin inhibiting activity(TIA/CIA= 1.0) with the independent reactive site to each enzyme. Dissociation constant of trypsin-BBTI and chymotrypsin-BBTl complexes were $9.17{\times}10^{-9}M$ and $5.14{\times}10^{-8}M$, respectively. Inhibitor Vll was extremely heat stable. Six hours heat treatment at $100^{\circ}C$ caused only 50% decrease in it's original inhibiting activity. Except inhibitor III,6 other isoinhibitors differed from a typical BBTI in TIA/CIA, values, ranging from 3 to 29.

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Studies on the Adenosine Deaminase Inhibitor Producing Actinomycetes J144-K (방선균 J-144K가 생산하는 Adenosine Deaminase Inhibitor에 관한 연구)

  • Jun, Hong-Ki;Kim, Sam-Woong;Jo, Young-Bae;Yeeh, Yeehn
    • Journal of Life Science
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    • v.6 no.2
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    • pp.120-128
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    • 1996
  • In the screening of actinomycetes culture filtrate for inhibitor of adenosine deaminase, a novel inhibitor was found in a cultured broth of strain J-144K. The optimum conditions for the adenosine deaminase inhibitor production from the isolated strain J-144K were evaluated. This strain showed the maximum yield of adenosine deaminase inhibitor when grown at pH 7.0 and 30$\circ$C for 60 hours in the medium of 1.0% dextrose, 0.5% yeast extract, 0.5% peptone and 0.1% KH$_{2}$PO$_{4}$ under the aerobic condition. Through the activated charcoal extraction, methanol fractionation, Dowex 50 H$^{+}$ X-8 ion exchange column chromatography, Dowex CI$^{-}$ X-8 ion exchange column chromatography, and Sephadex G-15 gel filtration procedures, this inhibitor was purified with three materials.

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Production and Physico-chemical Properties of Cathepsin B Inhibitor from Streptomyces aburabiensis SMF 30 (Streptomyces aburabiensis SMF30이 생산하는 Cathepsin B 저해물질의 발효생산 및 특성분석)

  • 최영출;김인섭;박상진;윤성준;이계준
    • YAKHAK HOEJI
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    • v.39 no.3
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    • pp.306-313
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    • 1995
  • The aim of the present study was to produce low molecular weight cathepsin B inhibitor. A strain of Streptomyces aburabiensis isolated from soil in Korea was selected and the optimum condition for the production of the inhibitor was evaluated. Glucose and soytone were selected as best carbon and nitrogen sources, respectively. From the kinetic analysis in batch fermentation, it was found that the specific cathepsin B inhibitor production rate (q$_{p}$) was linearly related to specific growh rate ($\mu$). The inhibitor in culture filtrate was purified by adsorption on activated charcoal, butanot extraction, silica gel chromatography, ion exchange chromatography using Dowex-1 (Cl form) and Amberlite IRC-50 (H$^{+}$ form), and preparative TLC. From the UV, IR, Mass spectroscopy and $^{1}$H-NMR, the inhibitor was thought to be a new inhibitor of which molecular weight was 199.

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Purification and Characterization of Aminoglycoside-Resistant inhibitior from methylotrophic Actinomycetes (Methanol 자화 방선균으로부터 Aminoglycoside 내성 저해물질의 정제 및 특성)

  • 김현수;신재욱
    • Microbiology and Biotechnology Letters
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    • v.27 no.3
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    • pp.215-222
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    • 1999
  • Methylotrophic actinomycetes No. 155 produced an aminoglycoside antibiotics(AG)-resistant inhibitor. We have previously reported that the inhibitor shows strong inhibition to sisomicin-resistant strain. In order to understand the functions of inhibitor and sisomicin-resistance, characterizations and purification of inhibitor were investigated. Strain No. 155 was tentatively identified as Nocardiopsis sp. based on morphological and some physiological characteristics. In the antimicrobial activity test, the addition of inhibitor to sisomicin showed a reduction effect of MIC on the test strains such as Gram(+), Gram(-) bacteria and yeasts. The combination of the inhibitor and various antibiotics revealed synergistic against E. coli K-12 and B. subtilis PCI 219. The induced intracellular proteins from sisomicin-resistant strain exhibited the sisomicin inactivation by invitro test. And the induced intracellular proteins were inactivated by addition of the inhibitor. The inhibitor compound was purified by anion exchange chromatography(Dowex-1) and HPLC using Asahipak ES-502C column. The purified inhibitor compound was detected in a single peak(above 98.5% purity) through the HPLC analysis.

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