• Title/Summary/Keyword: catalytic factor

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여정자 추출물의 Tyrosinase 및 MITF 발현 억제 효과 (Inhibitory Effect of Fructus Ligustri Lucidi on Tyrosinase and MITF Expressions)

  • 한규수;김대성;우원홍;문연자
    • 동의생리병리학회지
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    • 제24권2호
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    • pp.296-301
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    • 2010
  • The purpose of this study was to investigate the mechanism of Hexane extract of Fructus Ligustri Lucidi (HFLL)-induced regulation of melanogenesis. An apparent down-regulatory effect of tyrosinase activity was observed when B16F10 cells were incubated with HFLL. Interestingly, HFLL did not inhibit the catalytic activity of cell-free tyrosinase from B16F10 cells, whereas kojic acid directly inhibited tyrosinase activity. Regarding protein levels of melanogenic enzymes, the amounts of tyrosinase and tyrosinase-related protein 1 (TRP-1) were decreased by HFLL, while the amount of tyrosinase-related protein 2 (TRP-2) slightly was reduced after incubation with HFLL. Treatment with HFLL was found to down-regulate microphthalmia-associated transcription factor (MITF). These results suggest that HFLL is an effective inhibitor of pigmentation caused by down regulation via MITF, tyrosinase, and TRP-1 expressions.

Nrf2 영구 넉다운 난소암 세포주의 Proteasome 저해 항암제 Bortezomib에 대한 감수성 증가 (Enhanced Sensitivity to Proteasome Inhibitor Bortezomib in Nrf2 Knockdown Ovarian Cancer Cells)

  • 이상환;최보현;곽미경
    • 약학회지
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    • 제55권6호
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    • pp.466-472
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    • 2011
  • NF-E2-related factor 2 (Nrf2), a master regulator of antioxidant genes in animals, has been associated with the resistance of cancer cells to several cytotoxic chemotherapeutics. Bortezomib, a reversible inhibitor of the 26S proteasome, is a novel class anti-cancer therapeutics approved for the treatment of refractory multiple myeloma. However, the molecular mechanism of drug-resistance remains elusive. In the present study, bortezomib sensitivity has been investigated in Nrf2 knockdown ovarian cancer cells. When Nrf2 expression is stably repressed using interfering RNA expression, bortezomib-induced apoptosis and cell death were significantly enhanced compared to nonspecific RNA control cells. Knockdown cells showed elevated expression in the catalytic subunit PSMB5, PSMB6, and PSMB7 compared to the control, and failed to induce heme oxygenase-1 expression following bortezomib treatment. These indicate that differential proteasome levels and altered expression of stress-response genes could be underlying mechanisms of bortezomib sensitization in Nrf2-inhibited ovarian cancer cells.

Structural Basis of the Disease-related Proteins: Target Oriented Structural Proteomics

  • Jinho Moon;Heo, Yong-Suk;Kim, Young-Kwan;Kim, Hye-Yeon;Park, Min-Hye;Hwang, Kwang-Yeon
    • 한국결정학회:학술대회논문집
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    • 한국결정학회 2003년도 춘계학술연구발표회
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    • pp.15-15
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    • 2003
  • To discover new drugs more quickly and more efficiently, pharmaceutical companies and biotechnology firms are increasingly turning to the genomics and the structural proteomics technologies. Structural-proteomics can provide a foundation for this through the determination and analysis for protein structure on a genomics scale. Among many structures determined by CGI, we will present with the representative examples drawn from our work on novel structures or complex structures of the disease-related proteins. The alpha subunit of Hypoxia-inducible factor (HIF) is targeted for degradation under normoxic conditions by an ubiquitin-ligase complex that recognizes a hydroxylated proline residue in HIF. Hydroxylation is catalysed by HIF prolyl 4-hydroxylases (HIFPH) which are fe(II) and 2-oxoglutarate (2-OG) dependent oxygenases. Here, we discuss the first crystal structure of the catalytic domain of HIFPH in complexes, with the Fe(II)/2-OG at 1.8Å. These structures suggest that the Ll region (residues 236-253), which is also conserved in mammals, form a 'lid' that closes over the active site. The structural and mutagenesis analyses allow us to provide a focus for understanding cellular responses to hypoxia and a target for the therapeutic manipulation.

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Optimization of photo-catalytic degradation of oil refinery wastewater using Box-Behnken design

  • Tetteh, Emmanuel Kweinor;Naidoo, Dushen Bisetty;Rathilal, Sudesh
    • Environmental Engineering Research
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    • 제24권4호
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    • pp.711-717
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    • 2019
  • The application of advanced oxidation for the treatment of oil refinery wastewater under UV radiation by using nanoparticles of titanium dioxide was investigated. Synthetic wastewater prepared from phenol crystals; Power Glide SAE40 motor vehicle oil and water was used. Response surface methodology (RSM) based on the Box-Behnken design was employed to design the experimental runs, optimize and study the interaction effects of the operating parameters including catalyst concentration, run time and airflow rate to maximize the degradation of oil (SOG) and phenol. The analysis of variance and the response models developed were used to evaluate the data obtained at a 95% confidence level. The use of the RSM demonstrated the graphical relationship that exists between individual factors and their interactive effects on the response, as compared to the one factor at time approach. The obtained optimum conditions of photocatalytic degradation are the catalyst concentration of 2 g/L, the run time of 30 min and the airflow rate of 1.04 L/min. Under the optimum conditions, a 68% desirability performance was obtained, representing 81% and 66% of SOG and phenol degradability, respectively. Thus, the hydrocarbon oils were readily degradable, while the phenols were more resistant to photocatalytic degradation.

Structural Basis of the Disease-related Proteins: Target Oriented Structural Proteomics

  • Hwang, Kwang-Yeon;Lee, Tae-Gyu;Kim, Jin-Hwan;Jeon, Young-Ho;Seonggu Ro;Cho, Joong-Myung
    • 한국생물물리학회:학술대회논문집
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    • 한국생물물리학회 2003년도 정기총회 및 학술발표회
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    • pp.28-28
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    • 2003
  • To discover new drugs more quickly and more efficiently, pharmaceutical companies and biotechnology firms are increasingly turning to the genomics and the structural proteomics technologies. Structural-proteomics can provide a foundation for this through the determination and analysis for protein structure on a genomics scale. Among many structures determined by CGI, we will present with the representative examples drawn from our work on novel structures or complex structures of the disease-related proteins. The alpha subunit of Hypoxia-inducible factor (HIF) is targeted for degradation under normoxic conditions by an ubiquitin-ligase complex that recognizes a hydroxylated proline residue in HIF, Hydroxylation is catalysed by HIF prolyl 4-hydroxylases (HIFPH) which are Fe(II) and 2-oxoglutarate (2-OG) dependent oxygenases. Here, we discuss the first crystal structure of the catalytic domain of HIFPH in complexes, with the Fe(II)/2-OG at 1.8 ${\AA}$. These structures suggest that the L1 region (residues 236-253), which is also conserved in mammals, form a ‘lid’ that closes over the active site. The structural and mutagenesis analyses allow us to provide a focus for understanding cellular responses to hypoxia and a target for the therapeutic manipulation.

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Description of Cellobiohydrolases Ce16A and Ce17A from Trichoderma reesei Using Langmuir-type Models

  • Kim, Dong-Won;Hong, Young-Gwan
    • Biotechnology and Bioprocess Engineering:BBE
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    • 제6권2호
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    • pp.89-94
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    • 2001
  • The binding of cellobiohydrolases to cullulose is a crucial initial step in cellulose hydrolysis. In the search for a detailed understanding of the function of cellobiohydrolases, much information concerning how the enzymes and their constituent catalytic and cellulose-binding changes during hydrolysis is still needed. The adsorption of purified two cellobiohydrolases (Ce17A and Ce16A) from Trichoderma reesei cellulase to microcrystalline cellulose has been studied. Cellobiohydrolase II (Ce16A) does not affect the adsorption of cellobiohydrolase I (Ce17A) significantly, and there are specific binding sites for both Ce17A and Ce16A. The adsorption affinity and tightness of the cullulase binding domain (CBD) for Ce17A are larger than those of the CBD for Ce16A. The CBD for Ce17A binds more rapidly and tightly to Avicel than the CBD for Ce16A. The decrease in adsorption observed when the two cellobihydrolases are studied together would appear to be the result of competition for binding sites on the cellulose. Ce17A competes more efficiently for binding sites than Ce16A. Competition for binding sites is the dominating factor when the two enzymes are acting together, furthermore adsorption to sites specific for Ce17A and Ce16A, also contributes to the total adsorption.

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5,000마력급 선박엔진용 SCR 반응기 유동 균일도에 관한 수치해석 (A Numerical Analysis on Flow Uniformity of SCR Reactor for 5,000PS Grade Marine Engine)

  • 이중섭;정인국;서정세;박창대;정경열
    • 한국기계가공학회지
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    • 제11권6호
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    • pp.28-35
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    • 2012
  • This study is on SCR reactor, NOx reduction system in Marine that has been an issue nowadays. Especially design data was obtained by numerical on flow uniformity that is one of the design factor in SCR reactor. Also pressure drop on catalyst size inserted into SCR reactor was compared by experiment and numerical analysis. S/W, numerical analysis used for this study was confirmed that the result of numerical analysis used STAR-CCM+, common use CFD code, pressure drop on catalyst is not big different from the result of numerical analysis. In addition, degree of uniformity of liquid on SCR reactor was over 0.9. Whereas it was assured that degree of uniformity of liquid was changed depends on the shape of pipe at the entrance of SCR.

HIF-1-Dependent Induction of Jumonji Domain-Containing Protein (JMJD) 3 under Hypoxic Conditions

  • Lee, Ho-Youl;Choi, Kang;Oh, Hookeun;Park, Young-Kwon;Park, Hyunsung
    • Molecules and Cells
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    • 제37권1호
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    • pp.43-50
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    • 2014
  • Jumonji domain-containing proteins (JMJD) catalyze the oxidative demethylation of a methylated lysine residue of histones by using $O_2$, ${\alpha}$-ketoglutarate, vitamin C, and Fe(II). Several JMJDs are induced by hypoxic stress to compensate their presumed reduction in catalytic activity under hypoxia. In this study, we showed that an H3K27me3 specific histone demethylase, JMJD3 was induced by hypoxia-inducible factor (HIF)-$1{\alpha}/{\beta}$ under hypoxia and that treatment with Clioquinol, a HIF-$1{\alpha}$ activator, increased JMJD3 expression even under normoxia. Chromatin immunoprecipitation (ChIP) analyses showed that both HIF-$1{\alpha}$ and its dimerization partner HIF-$1{\beta}$/Arnt occupied the first intron region of the mouse JMJD3 gene, whereas the HIF-$1{\alpha}/{\beta}$ heterodimer bound to the upstream region of the human JMJD3, indicating that human and mouse JMJD3 have hypoxia-responsive regulatory regions in different locations. This study shows that both mouse and human JMJD3 are induced by HIF-1.

Metalloporphyrin의 Olefin Epoxidation과 분자궤도함수론적 고찰 (Metalloporphyrin Catalyzed Olefin Epoxidation and Molecular Orbital Study)

  • 여환진;신현천
    • 대한화학회지
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    • 제36권4호
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    • pp.558-564
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    • 1992
  • 여러 가지 치환기를 가지는 망간 포피린착물을 촉매로 사용하여 CH$_2$Cl$_2$ 용매하에서 styrene과 NaOCl간의 반응에 대한 수율을 구하였다. ortho 위치에 치환기를 가지는 망간 포피린 착물과 전자받게성의 치환기를 가지는 망간 포피린착물일 때 반응속도와 에폭사이드에 대한 선택성이 증가했다. 또한 망간 포피린착물에 축상 리간드로서 이미다졸을 도입할 때 반응속도와 에폭사이드에 대한 선택성이 증가했다. Michealis-Menten식을 이용한 반응속도론적 연구에 의하면 착물의 촉매능에 더 큰 영향을 주는 요소는 $K_m$ 임을 알았다. $K_m$ 값이 작을수록 더 큰 결합친화도를 가진다. 이론적인 연구로 EHMO계산에 의해 나온 결과와 실험에 의해 나온 결과는 좋은 일치를 보여주었다.

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cAMP Response Element-Binding Protein- and Phosphorylation-Dependent Regulation of Tyrosine Hydroxylase by PAK4: Implications for Dopamine Replacement Therapy

  • Won, So-Yoon;You, Soon-Tae;Choi, Seung-Won;McLean, Catriona;Shin, Eun-Young;Kim, Eung-Gook
    • Molecules and Cells
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    • 제44권7호
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    • pp.493-499
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    • 2021
  • Parkinson's disease (PD) is characterized by a progressive loss of dopamine-producing neurons in the midbrain, which results in decreased dopamine levels accompanied by movement symptoms. Oral administration of l-3,4-dihydroxyphenylalanine (L-dopa), the precursor of dopamine, provides initial symptomatic relief, but abnormal involuntary movements develop later. A deeper understanding of the regulatory mechanisms underlying dopamine homeostasis is thus critically needed for the development of a successful treatment. Here, we show that p21-activated kinase 4 (PAK4) controls dopamine levels. Constitutively active PAK4 (caPAK4) stimulated transcription of tyrosine hydroxylase (TH) via the cAMP response element-binding protein (CREB) transcription factor. Moreover, caPAK4 increased the catalytic activity of TH through its phosphorylation of S40, which is essential for TH activation. Consistent with this result, in human midbrain tissues, we observed a strong correlation between phosphorylated PAK4S474, which represents PAK4 activity, and phosphorylated THS40, which reflects their enzymatic activity. Our findings suggest that targeting the PAK4 signaling pathways to restore dopamine levels may provide a new therapeutic approach in PD.