• Title/Summary/Keyword: Complex I

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Effects of camptothecin on the expression of DNA topoisomerase I and c-myc in HL-60 human leukemia cells (HL-60 사람 백혈병 세포에서 camptothecin이 DNA topoisomerase l과 c-myc의 발현에 미치는 영향)

  • 정인철;정대성;류경자;박장수;조무연
    • Journal of Life Science
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    • v.10 no.6
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    • pp.621-629
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    • 2000
  • Camptothecin (CPT) is an antitumor alkaloid that has been isolated from the Chinese tree, Camptotheca acuminata. The cytotoxicity of CPT has been correlated to its inhibition of DNA topoisomerase (Topo) I by stabilizing drug-enzyme-DNA “cleavable complex" resulting in DNA single-strand breaks and DNA-protein crosslinks. This studies were designed to elucidate whether CPT regulates Topo I mediated by CPT in DNAs containing c-myc protooncogene. We have conducted experiments on Topo I purification, pUC-MYC I cloning and Topo I assay using electrophoresis, quantitative RT-PCR and Northern blotting techniques. CPT ingibited the relaxation activity of Topo I in pUC19 DNA at various concentrations (1-1000 $\mu$M), while it enhanced the cleavage of Topo I in the pUC-MYC I by forming a cleavable complex at relatively high concentrations (100-1000 $\mu$M). In HL-60 cells treated with CPT, the expression of c-myc gene was decreased over that in the control group with no changes in the expression of Topo I mRNA. Our results suggest that Topo I is the target of CPT cytotoxicity but it does not affect Topo I extression, and the suppression of c-myc mRNA expression by CPT is due to c-myc damage resulted from formation of a cleavable complex with CPT. CPT.

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NORMAL INTERPOLATION ON AX=Y AND Ax=y IN A TRIDIAGONAL ALGEBRA $ALG\mathcal{L}$

  • Kang, Joo-Ho
    • Journal of applied mathematics & informatics
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    • v.24 no.1_2
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    • pp.535-539
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    • 2007
  • Given operators X and Y acting on a separable complex Hilbert space $\mathcal{H}$, an interpolating operator is a bounded operator A such that AX=Y. In this article, we show the following: Let $Alg\mathcal{L}$ be a tridiagonal algebra on a separable complex Hilbert space $\mathcal{H}$ and let $X=(x_{ij})\;and\;Y=(y_{ij})$ be operators in $\mathcal{H}$. Then the following are equivalent: (1) There exists a normal operator $A=(a_{ij})\;in\;Alg\mathcal{L}$ such that AX=Y. (2) There is a bounded sequence $\{\alpha_n\}\;in\;\mathbb{C}$ such that $y_{ij}=\alpha_jx_{ij}\;for\;i,\;j\;{\in}\;\mathbb{N}$. Given vectors x and y in a separable complex Hilbert space $\mathcal{H}$, an interpolating operator is a bounded operator A such that Ax=y. We show the following: Let $Alg\mathcal{L}$ be a tridiagonal algebra on a separable complex Hilbert space $\mathcal{H}$ and let $x=(x_i)\;and\;y=(y_i)$ be vectors in $\mathcal{H}$. Then the following are equivalent: (1) There exists a normal operator $A=(a_{ij})\;in\;Alg\mathcal{L}$ such that Ax=y. (2) There is a bounded sequence $\{\alpha_n\}$ in $\mathbb{C}$ such that $y_i=\alpha_ix_i\;for\;i{\in}\mathbb{N}$.

Functional Expression of Saccharomyces cerevisiae NADH-quinone Oxidoreductase (NDI1) Gene in the AML12 Mouse Liver Hepatocytes for the Applying Embryonic Stem Cell

  • Seo, Byoung-Boo;Park, Hum-Dai
    • Reproductive and Developmental Biology
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    • v.35 no.4
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    • pp.427-434
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    • 2011
  • Mitochondria diseases have been reported to involve structural and functional defects of complex I-V. Especially, many of these diseases are known to be related to dysfunction of mitochondrial proton-translocating NADH-ubiquinone oxidoreductase (complex I). The dysfunction of mitochondria complex I is associated with neurodegenerative disorders, such as Parkinson's disease, Huntington's disease, and Leber's hereditary optic neuropathy (LHON). Mammalian mitochondrial proton-translocating NADH-quinone oxidoreductase (complex I) is largest and consists of at least 46 different subunits. In contrast, the NDI1 gene of Saccharomyces cerevisiae is a single subunit rotenone-insensitive NADH-quinone oxidoreductase that is located on the matrix side of the inner mitochondrial membrane. The Saccharomyces cerevisiae NDI1 gene using a recombinant adeno-associated virus vector (rAAV-NDI1) was successfully expressed in AML12 mouse liver hepatocytes and the NDI1-transduced cells were able to grow in media containing rotenone. In contrast, control cells that did not receive the NDI1 gene failed to survive. The expressed Ndi1 enzyme was recognized to be localized in mitochondria by confocal immunofluorescence microscopic analyses and immunoblotting. Using digitonin-permeabilized cells, it was shown that the NADH oxidase activity of the NDI1-transduced cells was not affected by rotenone which is inhibitor of complex I, but was inhibited by antimycin A. Furthermore, these results indicate that Ndi1 can be functionally expressed in the AML12 mouse liver hepatocytes. It is conceivable that the NDI1 gene is powerful tool for gene therapy of mitochondrial diseases caused by complex I deficiency. In the future, we will attempt to functionally express the NDI1 gene in mouse embryonic stem (mES) cell.

Selective cytotoxicity of a novel mitochondrial complex I inhibitor, YK-135, against EMT-subtype gastric cancer cell lines due to impaired glycolytic capacity

  • Yeojin, Sung;Seungbin, Cha;Sang Bum, Kim;Hakhyun, Kim;Seonghwi, Choi;Sejin, Oh;Minseo, Kim;Yunji, Lee;Gino, Kwon;Jooyoung, Lee;Joo-Youn, Lee;Gyoonhee, Han;Hyun Seok, Kim
    • BMB Reports
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    • v.55 no.12
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    • pp.645-650
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    • 2022
  • Epithelial-to-mesenchymal transition (EMT)-subtype gastric cancers have the worst prognosis due to their higher recurrence rate, higher probability of developing metastases and higher chemo-resistance compared to those of other molecular subtypes. Pharmacologically actionable somatic mutations are rarely found in EMT-subtype gastric cancers, limiting the utility of targeted therapies. Here, we conducted a high-throughput chemical screen using 37 gastric cancer cell lines and 48,467 synthetic small-molecule compounds. We identified YK-135, a small-molecule compound that showed higher cytotoxicity toward EMT-subtype gastric cancer cell lines than toward non-EMT-subtype gastric cancer cell lines. YK-135 exerts its cytotoxic effects by inhibiting mitochondrial complex I activity and inducing AMP-activated protein kinase (AMPK)-mediated apoptosis. We found that the lower glycolytic capacity of the EMT-subtype gastric cancer cells confers synthetic lethality to the inhibition of mitochondrial complex I, possibly by failing to maintain energy homeostasis. Other well-known mitochondrial complex I inhibitors (e.g., rotenone and phenformin) mimic the efficacy of YK-135, supporting our results. These findings highlight mitochondrial complex I inhibitors as promising therapeutic agents for EMT-subtype gastric cancers and YK-135 as a novel chemical scaffold for further drug development.

EXCITED-STATE TWISTED INTRAMOLECLILAR CHARGE TRANSFER OF p-N,N-DIMETHYLAMINOBENZOIC ACID IN AQUEOUS CYCLODEXTRIN SOLUTIONS: TIME-RESOLVED FLUORESCENCE STUDY

  • Kim, Yong-Hee;Cho, Dae-Won;Yoon, Min-Joong
    • Journal of Photoscience
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    • v.3 no.3
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    • pp.153-158
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    • 1996
  • The effects of $\alpha$- and $\beta$-cyclodextrins (CD) on the twisted intramolecular charge transfer (TICT) behavior of p-N,N'-dimethylaminobenzoic acid (DMABA) in buffered aqueous solution have been investigated by examining formation and decay behaviors of the TICT-typical dual fluorescence. The ratio of the TICT emission to the normal emission (I$_a$/I$_b$) increases linearly $\alpha$-CD concentration increases, while in the presence of $\beta$-CD it shows nonlinear dependences on the CD concentration. The analysis of the CD-dependent changes of the I$_a$/I$_b$ and absorption spectra demonstrates formation of 1:1 inclusion complexes between DMABA and CDs. The decay time of the normal emission (ca. 700 ps) is little affected by the formation of $\alpha$-CD inclusion complex, whereas it increases upto ca. 1.6 ns upon formation of $\beta$-CD inclusion complex. The TICT emission for the $\beta$-CD inclusion complex exhibits two decay components while it shows a single component for the $\alpha$-CD inclusion complex, indicating formation of one or two types of inclusion complex in the presence of $\alpha$-CD or $\beta$-CD, respectively. These results are attributed to the CD cavity size dependence on patterns of complexation between CDs and DMABA. The CD size dependences of the TICT fluorescence properties with the orientation of the guest molecule demonstrate that the specific hydrogen bonding between the carboxylic acid group and water plays an important role in the excited-state TICT.

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Stress and Deformation Analysis of a Tool Holder Spindle using $iSight^{(R)}$ ($iSight^{(R)}$를 이용한 툴 홀더 스핀들의 변형 및 응력해석)

  • Kwon, Koo-Hong;Chung, Won-Jee
    • Journal of the Korean Society for Precision Engineering
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    • v.27 no.9
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    • pp.103-110
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    • 2010
  • This paper presents the optimized approximation of finite element modeling for a complex tool holder spindle using both DOE (Design of Experiment) with Optimal Latin Hypercube (OLH) method and approximation modeling method with Radial Basis Function (RBF) neural network structure. The complex tool holder is used for holding a (milling/drilling) tool of a machine tool. The engineering problem of complex tool holder results from the twisting of spindle of tool holder. For this purpose, we present the optimized approximation of finite element modeling for a complex tool holder spindle using both DOE (Design of Experiment) with Optimal Latin Hypercube (OLH) method (specifically a module of $iSight^{(R)}$ FD-3.1) and approximation modeling method with Radial Basis Function (RBF) (another module of $iSight^{(R)}$ FD-3.1) neural network structure

Synthesis and structure analysis of the bis(dicyclohexylammonium) chromate dihydrate complex, [(C6H11)2NH2]2[CrO4]·2H2O

  • Kim, Chong-Hyeak;Moon, Hyoung-Sil;Lee, Sueg-Geun
    • Analytical Science and Technology
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    • v.20 no.5
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    • pp.448-451
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    • 2007
  • A new bis(dicyclohexylammonium) chromate dihydrate complex, $[(C_6H_{11})_2NH_2]_2[CrO_4]{\cdot}2H_2O$, (I), has been synthesized and its structure analyzed by FT-IR, EDS, elemental analysis, ICP-AES, and single crystal X-ray diffraction methods. The Cr(VI) complex (I) is tetragonal system, I${\bar{4}}$2d space group with a = 12.5196(1), b = 12.5196(1), c = $17.3796(3){\AA}$, a = ${\beta}$ = ${\gamma}$ = $90^{\circ}$, V = $2724.09(6){\AA}^3$, Z = 4. The crystal structure of complex (I) consists of tetrahedral chromate $[CrO_4]^{2-}$ anion, two organic dicyclohexylammonium $[(C_6H_{11})_2NH_2]^+$ cations and two lattice water molecules. The chromate anion and protonated dicyclohexylammonium cation is mainly constructed through the ionic bond. The cyclohexylammonium rings of the dicyclohexylammonium cation take the chair form and vertical configuration with each other. The N-H${\cdot}$O and O-H${\cdot}$O hydrogen bond networks between the $N_{dicyclohexylammonium}$, $O_{water}$ and $O_{chromate}$ atom lead to self-assembled molecular conformation and stabilize the crystal structure.

Study on forest vegetation in the vicinity of onsan industrial complex (溫山工團 周邊의 森林植生에 관한 調査)

  • Kim, Jong-Gab
    • The Korean Journal of Ecology
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    • v.15 no.3
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    • pp.231-246
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    • 1992
  • In order to estimate effects of air pollution for pinus thunbergii forests arounding onsan industrial complex, structure of forest vegrtation was surveyed. In the survey of forest vegetation, pinus densiflora have been died or being withered, and importance value(I.V) of rhododendron mucromulatum and lespedeza spp. were low at the vicinity of industrial complex. Especially lespedeza maximowiczii and l. maritima were not entirely appeared at the vicinity of industrial complex. I.V. of quercus serrata, robinia pseudoacacia and alnus firma were preferably high at the vicinity of industrial complex, and those of smilax china, rubus crataegifolius and rhus trichocarpa were similar at every site and it could be guessed that those had a tolerance. Number of species had a difference over 10 species at the vicinity of industrial complex as compared with those of remote sites, and species diversity showed highly at the farther sites of industrial complex, and also at the low layer, number of species, species diversity and evennes were low at the vicinity of industrialcomplex and species weakened to air pollution were disappearing. It was possible that forest vegetation would be changed from pinus spp. to community of a. firma and r. pseudoacacia.

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The Historical Background of the Development of Changwon Industrial Complex: A Geopolitical Economy Approach (지리정치경제학적 관점에서 본 창원공단 설립 전사(前史))

  • Choi, Young Jin
    • Journal of the Korean Geographical Society
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    • v.49 no.2
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    • pp.178-199
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    • 2014
  • Changwon Industrial Complex is commonly framed as the best example of strong initiative of the Korean developmental state. And this explanation has been given in the theoretical frame of 'neo-Weberian accounts' i.e., strongly 'national-territorial' and state-centric terms of the predominant. I argue that a geopolitical economy approach focusing on the historical background of the development of Changwon Industrial Complex will shed light on crucial sociospatial dimensions of the Korean developmental state's industrial complex success. I examine, in particular, the multi-scalar processes through which the changes of the industrial complex building plans for the promotion of machine industry in 1960's have been influenced by the complex and dynamic interactions among social actors acting at diverse geographical scales. I show that the formation of the industrial complex in Korea was more heavily influenced by the interactions, contestations, and collaborations among social actors, acting in and through the state, rather than by the state initiative.

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