• Title/Summary/Keyword: REF

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The Role of Ref-1 in the Differentiation Process of Monocytic THP-1 Cells (단핵구세포주 THP-1의 분화과정에서 Ref-1의 역할)

  • Da Sol Kim;Kang Mi Kim;Koanhoi Kim;Young Chul Park
    • Journal of Life Science
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    • v.34 no.4
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    • pp.271-278
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    • 2024
  • Redox factor (Ref)-1, a ubiquitously expressed protein, acts as a modulator of redox-sensitive tran- scription factors and as an endonuclease in the repair pathway of damaged DNA. However, the function of Ref-1 in the differentiation of monocytes into macrophages has not been defined. In this study, we investigated the effects of Ref-1 on the monocyte differentiation process using the human monocytic cell line THP-1. The differentiation agent PMA increased cell adhesion over time and showed a sig- nificant increase in phagocytic function but decreased the intracellular amount of Ref-1. Ref-1 inhibitor E3330 and Ref-1 knockdown using the siRNA technique reduced cell adhesion and the expression of differentiation markers, such as CD14, ICAM-1, and CD11b, by PMA stimulation. This means that the role of Ref-1 is absolutely necessary in the initial process of differentiating THP-1 cells stimulated by PMA. Next, the distribution of Ref-1 was examined in the cytoplasm and nucleus of THP-1 cells stimulated with PMA. Surprisingly, PMA stimulation resulted in the rapid translocation of Ref-1 to the nucleus. To prove that movement of Ref-1 to the nucleus is required for monocyte differentiation, a Ref-1 vector with the nuclear localization sequence (NLS) deleted was used. As a result, overexpression of ∆NLS Ref-1, which restricted movement to the nucleus, suppressed the expression of differentiation markers and notably reduced phagocytic function in PMA-stimulated THP-1 cells. In conclusion, these data suggest that the differentiation of monocytic THP-1 cells requires Ref-1 nuclear translocation during the initial process of biochemical events following stimulation from PMA.

Adenoviral-Mediated Ref-1 Overexpression Potentiates NO Production in Bradykinin-Stimulated Endothelial Cells (Bradykinin으로 자극한 혈관내피세포에서 Ref-1의 세포내 과발현에 의한 NO 생성 증진 효과에 대한 연구)

  • Song, Ju-Dong;Kim, Kang-Mi;Lee, Sang-Kwon;Kim, Jong-Min;Park, Young-Chul
    • Journal of Life Science
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    • v.17 no.7 s.87
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    • pp.905-909
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    • 2007
  • The dual-function protein redox factor-1 (Ref-1) is essential for base excision repair of oxidatively damaged DNA and also governs the activation of many redox-sensitive transcription factors. We examined the role of Ref-1 in regulation of nitric oxide (NO) synthesis employing adenoviral-mediatedoverexpression of Ref-1 in bradykinin-stimulated endothelial cells. Intracellular NO was detected with the NO-sensitive fluorophore DAF-2. Overexpression of Ref-1 potentiates bradykinin-stimulated NO production in endothelial cells. And, cells ifected with AdRef-1 showed higher fluorescence intensity compared with uninfected or AdD1312-infected cells. In parallel with this, over expression of Ref-1 also stimulated endothelial NO synthase (eNOS) enzyme activity, compared with unifected or AdD1312-infected cells, in bradykinin-stimulated cells as well as in unstimulated cells. These results suggest that Ref-1 implicates in endothelium-dependent vasorelaxation resulting from NO production in vascular system.

Effect of Overexpressed Ref-1 on AKT Phosphorylation for NO Production in Mouse Aortic Endothelial Cell Line (마우스 내피세포주 MAE의 NO 생성과정에서 과발현된 Ref-1의 AKT 활성 조절에 대한 연구)

  • Song, Ju-Dong;Lee, Sang-Kwon;Park, Young-Chul
    • Journal of Life Science
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    • v.18 no.12
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    • pp.1651-1656
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    • 2008
  • Redox factor-1 (Ref-1) is essential for repair of oxidatively damaged DNA and also govern the reductive activation of many transcription factors. In this study, we examined the effect of overexpressed Ref-1 on AKT activation for nitric oxide (NO) production in mouse aortic endothelial (MAE) cells. Adenoviral-mediated overexpression of Ref-1 enhanced NO production in unstimulated- as well as bradykinin-stimulated MAE cells. Importantly, forced overexpression of Ref-1 induced direct phosphorylation of AKT in cells. And, a PI3K inhibitor wortmannin completely abolished the increase in AKT phosphorylation by stimulation of bradykinin and/or overexpressed Ref-1. In addition, inhibition of AKT activity with HA-tagged activation-deficient AKT suppressed Ref-1-induced endothelial NO synthase (eNOS) phosphorylation and resulted in a corresponding inhibition of unstimulated- and bradykinin-stimulated NO production. These results suggest that Ref-1 stimulates direct phosphorylation of AKT for eNOS enzyme activity in murine endothelial cells.

Detection of Ref-1 (Redox factor-1) Interacting Protein Using the Yeast Two-hybrid System (Yeast two-hybrid system을 이용한 Ref-1 (redox factor-1) 결합 단백질의 분리 및 동정)

  • 이수복;김규원;배문경;배명호;정주원;안미영;김영진
    • Journal of Life Science
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    • v.14 no.1
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    • pp.26-31
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    • 2004
  • Redox factor-1 (Ref-1), known as a redox regulator, controls the DNA binding of AP-1 and is activated in HT29 colon cancer cells by hypoxia in vitro. REF-1 also increases tile DNA binding affinity of Hypoxia-inducible Factor-lalpha$ (HIF-lalpha$), HIF-like Factor (HLF) and early growth response-1 (Egr-1) which induce expression of the genes involved in angiogenesis, so that we speculate that REF-1 may play a role in hypoxia-induced angiogenesis. In this research we tried to detect novel proteins interacting with REF-1 using Yeast two-hybrid system using full-length REF-1 cDNA as bait. As result of such screening we detected 3 positive clones. DNA sequencing and GeneBank search revealed that one of the clones contained the same sequences as M.musculus cDNA for tioredoxin.

Ape1/Ref-1 Stimulates GDNF/GFR ${\alpha}$ 1-mediated Downstream Signaling and Neuroblastoma Proliferation

  • Kang, Mi-Young;Kim, Kweon-Young;Yoon, Young;Kang, Yoon-Sung;Kim, Hong-Beum;Youn, Cha-Kyung;Kim, Dong-Hui;Kim, Mi-Hwa
    • The Korean Journal of Physiology and Pharmacology
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    • v.13 no.5
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    • pp.349-356
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    • 2009
  • We previously reported that glial cell line-derived neurotropic factor (GDNF) receptor ${\alpha}$ 1 (GFR ${\alpha}$ 1) is a direct target of apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1). In the present study, we further analyzed the physiological roles of Ape1/Ref-1-induced GFR ${\alpha}$ 1 expression in Neuro2a mouse neuroblastoma cells. Ape1/Ref-1 expression caused the clustering of GFR ${\alpha}$ 1 immunoreactivity in lipid rafts in response to GDNF. We also found that Ret, a downstream target of GFR ${\alpha}$ 1, was functionally activated by GDNF in Ape1/Ref-1-expressing cells. Moreover, GDNF promoted the proliferation of Ape1/Ref-1-expressing Neuro2a cells. Furthermore, GFR ${\alpha}$ 1-specific RNA experiments demonstrated that the downregulation of GFR ${\alpha}$ 1 by siRNA in Ape1/Ref-1-expressing cells impaired the ability of GDNF to phosphorylate Akt and PLC ${\gamma}$-1 and to stimulate cellular proliferation. These results show an association between Ape1/Ref-1 and GDNF/GFR ${\alpha}$ signaling, and suggest a potential molecular mechanism for the involvement of Ape1/Ref-1 in neuronal proliferation.

CrossRef the leading DOI service organization & DOI Center in KISTI (DOI 서비스의 중심 CrossRef와 KISTI의 DOI Center)

  • Oh, Hye-Min;Cho, Eun-Jin;Kang, Mu-Yeong
    • Proceedings of the Korean Society for Information Management Conference
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    • 2011.08a
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    • pp.67-70
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    • 2011
  • 국내학술지의 국제적 이용과 인용확대를 위해 국가출연기관인 한국과학기술정보연구원(KISTI)은 CrossRef에 Co-Sponsoring Member로 가입하여 디지털 콘텐츠의 식별과 접근을 위한 고유 식별 체계인 DOI(Digital Object Identifier) 번호부여 및 DOI 기탁사업을 추진해오고 있다. CrossRef는 논문, 회의자료, 단행본 자료의 DOI 기탁업무를 수행하는 전 세계적인 비영리기관이며 DOI에 기반하여 Cited-by linking 서비스를 시행하고 이용자들의 필요에 따른 다양한 학술서비스를 제공하고 있다. 따라서 본 논문에서는 CrossRef에서 시행하는 서비스인 DOI, CrossCheck, Cited-by linking을 소개하고 KISTI를 통한 CrossRef서비스와 KISTI에서 운영하는 DOI Center 대해 기술하고자 한다.

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A Study on the Development of DOI Lookup API (DOI 수집 API 개발에 관한 연구)

  • Kim, Sun-Tae;Yae, Yong-Hee
    • Journal of Information Management
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    • v.39 no.1
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    • pp.221-237
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    • 2008
  • CrossRef provides a various queries(OpenAPIs) which can be used for DOI & meta data lookup. CrossRef encourages publishers and library societies to develop diverse system by using the queries. In this thesis, CrossRef's queries are analyzed and DOI Lookup API which could automatically lookup the DOI by various methods was developed. I proposed that how institutions having their own meta data can use the developed API.

Estimation on Trends of Reference Evapotranspiration of Weather Station Using Reference Evapotranspiration Calculator Software (Reference Evapotranspiration Calculator Software를 이용한 기상관측소 기준증발산 추정)

  • Choi, Wonho;Choi, Minha;Oh, Hyunje;Park, Jooyang
    • KSCE Journal of Civil and Environmental Engineering Research
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    • v.30 no.2B
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    • pp.219-231
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    • 2010
  • The Reference Evapotranspiration Calculator Software (REF-ET) supports computational guidelines for the reference evapotranspiration using seventeen FAO Penman-Monteith (PM) equations simultaneously such as the ASCE and FAO standardized forms. The REF-ET can conveniently consider missing data predictions and regional site characterizations, when reference ET is computed on monthly, daily, and hourly time steps. The applicability of the REF-ET was estimated to simulate the reference ET using hourly weather data from Seoul weather station for 29 years. The result found that the FAO24-Rd and 1957-Makk equations closely concerned with solar radiation parameter which were the most highly correlated to reference ET computed by pan coefficient. In addition, the 1957-Makk equation was identified as the most correct computational method for reference ET by analysis of bias and root mean square error. The 1957-Makk equation could predict the reference ET within the error of less than 1.06 mm/day, though all the other equations tended toward overestimation of predicting the reference ET in comparison with refecence ET of pan. The results of this study suggest that the REF-ET will be applicable to support reference ET estimation for a variety of field condition and time-scale.

Overexpression of Ref-1 Inhibits Lead-induced Endothelial Cell Death via the Upregulation of Catalase

  • Lee, Kwon-Ho;Lee, Sang-Ki;Kim, Hyo-Shin;Cho, Eun-Jung;Joo, Hee-Kyoung;Lee, Eun-Ji;Lee, Ji-Young;Park, Myoung-Soo;Chang, Seok-Jong;Cho, Chung-Hyun;Park, Jin-Bong;Jeon, Byeong-Hwa
    • The Korean Journal of Physiology and Pharmacology
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    • v.13 no.6
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    • pp.431-436
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    • 2009
  • The role of apurinic/apyrimidinic endonuclease1/redox factor-1 (Ref-1) on the lead (Pb)-induced cellular response was investigated in the cultured endothelial cells. Pb caused progressive cellular death in endothelial cells, which occurred in a concentration- and time-dependent manner. However, Ref-1 overexpression with AdRef-1 significantly inhibited Pb-induced cell death in the endothelial cells. Also the overexpression of Ref-1 significantly suppressed Pb-induced superoxide and hydrogen peroxide elevation in the endothelial cells. Pb exposure induced the downregulation of catalase, it was inhibited by the Ref-1 overexpression in the endothelial cells. Taken together, our data suggests that the overexpression of Ref-1 inhibited Pb-induced cell death via the upregulation of catalase in the cultured endothelial cells.

A Study on Development of Integrated OPAC Based on Hypermedia Techniques (하이퍼미디어 기술에 기반한 통합 OPAC구현에 관한 연구)

  • Ahn, Tae Kyoung;Kim, Hyun Hee
    • Journal of Information Management
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    • v.27 no.1
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    • pp.1-39
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    • 1996
  • The purpose of this paper is to design a model of integrated OPAC called as EconRef. This model not only provides users of libraries with systematic, rapid information service, but also supports librarians to do their tasks effectively. The designed model is constructed based on two operating systems such as REGIS system and The Book House and is developed by using KPWin++ is an expert system shell which combines hypertext and expert system functions. The designed system consists of six modules ; three reference expert systems for document sources, experts and statistical sources; OPAC ; external database ; user's guide. For the evaluation of the designed system, performance of EconRef system is compared with that of the naive and expert reference librarians. And also the features of the system are compared with those of REGIS systems. The tests comparing BconRef system searching with librarians searching have shown that EconRef system is at least as good as searching with expert librarians and much superior to searching with naive librarians.

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