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      • Bipolar resistive switching characteristics of Ag/Mn:ZnO/ITO devices for non-volatile memory application

        양지연 Kongju National University 2018 국내석사

        RANK : 232975

        본 연구에서는 간단한 솔루션 기반 프로세스를 통해 Ag / Mn 도핑 된 ZnO / ITO 구성을 갖는 전기 화학적 금속화 기반의 저항 스위칭 메모리(ECM 기반 ReRAM) 소자에 대하여 연구하였다. Mn 도핑 된 ZnO는 수용성 고분자에 의해 배위 된, Mn- 및 Zn- 복합체를 사용하는 Polymer-assisted solution(PAS)으로 제조되었다. ReRAM의 상부 전극은 잉크젯 인쇄로 패턴 화되었다. Mn 도핑 ZnO 고체 전해질을 사용한 ECM 기반 ReRAM의 메모리 윈도우는 10보다 넓으며, 500 사이클 이상의 사이클 내구성 및 104 초보다 긴 유지 시간, 20ns의 빠른 프로그래밍 스피드로 바이폴라 저항 스위칭 동작을 확인할 수 있다. 높은 저항 상태와 낮은 저항 상태에서 전도 메커니즘을 분석하면, 저항 스위칭이 Mn을 도핑 한 ZnO 전해질 층을 통과하는 나노 크기의 Ag 전도 필라멘트의 형성 및 파열로 인한 결과임을 알 수 있다. 본 연구는 향후 비 휘발성 메모리 디바이스를 저비용으로 개발할 수 있는 솔루션 프로세스의 잠재력을 확인할 수 있다..

      • Exploration of promising chemical scaffolds for Alzheimer's disease using enzyme inhibition, computational modelling, molecular docking and dynamic simulation studies

        Mubasher Hassan Kongju National University 2019 국내박사

        RANK : 232975

        Alzheimer's disease (AD) is a neurodegenerative and multifactorial disorder prevails with ageing in human. The mutated genes and multiple synaptic/nonsynaptic proteins are the key regulator in the pathogenesis of AD. In the present research multiple AD related proteins such as β-secretase 1 (BACE1), amyloid-β42, Cas scaffolding protein family member 4 (CASS4) and protein tyrosine kinase 2 (PTK2), nicotine acetylcholine receptor α7 (nAChRα7) and acetyl/butyryl-cholinesterases (AChE and BChE) were used and analysed for the development of novel chemical scaffolds for the betterment of AD. Multiple clinical drugs and antibodies such as lanabecestat (AZD3293, (1)) and solanezumab are being used to investigate their therapeutical potential against AD. Using molecular dynamic (MD) simulation, the generated root mean square deviation and fluctuation (RMSD/F) graphs showed that AZD3293 residual fluctuations and RMSD value (0.2 nm) was better as compared to solanezumab (0.7 nm). Moreover, the radius of gyration (Rg) results also depicted the significance of AZD3293 docked complex compared to solanezumab through residual compactness. Our comparative results indicated that AZD3293 is a better therapeutic agent for treating AD than solanezumab. In another research work, i used protein-protein interactions study to explore the binding sites of different AD mediated signalling pathways proteins. The CASS4-PTK2 and Aβ42-nAChRα7 complexes are signalling proteins, which are involve in neuritic plaques burden, neurofibrillary tangles, and disruption of synaptic connections in AD. Protein-protein docking approach was employed to explore the active binding sites of CASS4-PTK2 and Aβ42-nAChRα7 complexes and their significant role in the activation of downstream signalling pathways. The protein sequential and structural analyses were performed on CASS4 and nAChRα7 to identify their core active binding sites residues. Furthermore, the stability of these docking complexes was confirmed by MD experiment by generating RMSD/F, Rg and SASA graphs. From the predicted results, it has been observed that a better understanding of CASS4 and nAChRα7 proteins could be used as therapeutic targets in the treatment for AD. Sulfonamides are generally used as promising inhibitors against AChE and BChE to treat AD. Three series of newly synthesized acetamides were optimised against AChE and BChE enzymes to prompt the best inhibitors for the betterment of AD. From the first bunch of sulphonamide derivatives, 6c showed good inhibitory potential against AChE with IC50 = 0.075 ± 0.001 μM as compared to standard (Neostigmine methylsulfate) value IC50 2.038 ± 0.039 μM. Furthermore, kinetic mechanism analysed by Lineweaver-Burk plots demonstrated that compound (6c) inhibits the AChE competitively to form an enzyme inhibitor complex. The inhibition constants Ki calculated from Dixon plots for compound (6c) is 2.5 μM. The molecular docking experiment also showed its good interactive profile against AChE within the active region of target protein. The other two series of sulfonamide derivatives were tested against both AChE and BChE to check their inhibitory potential. The 2-furoyl piperazine based sulfonamide derivatives were screened against BChE while, 2-bromo-N-(un/substituted)phenyl)acetamides were screened against both AChE and BChE, respectively. The cytotoxicity of these newly synthesized sulfonamides derivatives was also ascertained through hemolysis of bovine red blood cells. In 2-furoyl piperazine based sulfonamide derivatives, the enzyme inhibition results showed that 10c bearing an unsaturated chain (allyloxy group) behaved as a superb inhibitor with an IC50 value of 9.51 ± 0.06 μM. Whereas, 10j (IC50=17.69±0.07 μM) and 10k (IC50 =15.43±0.09 μM) were also showed good inhibitory potential compared to all other inhibitors. Similarly, the 2-bromo-N-(un/substituted)phenyl)acetamides derivative 14e was most potent and active inhibitor against both enzymes (AChE; IC50 = 5.54 ± 0.03 μM & BChE; IC50 = 9.15 ± 0.01 μM). Moreover, computational assessment against all sulphonamide derivatives was confirmed by RO5, lead optimization and ADMET calculations. There binding interactions were checked by molecular docking and dynamic simulation experiments. Based on our in vitro and in silico analyses 6c, 10c and 14e were identified as promising lead compounds and could be used as a good templates for the development of novel drugs against AD.

      • Role of organic label food in large supermarket : the influence of store image and organic label food satisfaction on organic food behavioral intentions

        안재윤 Kongju National University 2018 국내석사

        RANK : 232975

        목적 – 유기농식품, 유통사(대형 슈퍼마켓), 그리고 소비자 간의 다이나믹스를 탐구하는데 그 목적이 있다. 디자인/방법론/접근방법 - 개념적 모델이 적용 되었고 회귀분석 방법을 사용하였다. 결과 – 유기농 식품(라벨)은 그 자체로 브랜드와 유사한 기능을 수행하는 것으로 나타났다. 유기농식품의 만족도는 매장 이미지와 유기농식품 구매의도 간에 완전한 매개를 하는 것으로 나타났다. 그러나 유기농 식품에 대한 만족도가 매장의 만족도에 영향을 미치지는 않는 것으로 나타났다. 연구함의 – 대형슈퍼마켓내 유기농식품의 카테고리 매니지먼트를 효율적으로 운영할 수 있는 방법을 제시 하였다. 유기농식품 자체가 매장의 만족도에 영향을 주지 못하기 때문에 유기농 식품의 매대내 진열 공간을 축소하고 별도의 숍인숍으로 진행 되고 있는 부분도 재고려 대상이 될 수 있다. 반대로 유기농식품 공급자는 유기농식품이 대형슈퍼마켓의 소비자에게 크게 어필 하지 않음을 인지하고, 매장의 이미지를 고려하여 유기농식품 전문매장을 중심으로 납품이 진행 될 수 있도록 채널개발 전략을 세울 필요가 있음을 밝혔다. 연구제약 – 대형슈퍼마켓에서의 유기농식품 구매 동기는 유기농식품에서의 그것과 다르다. 또한, 대형슈퍼마켓내 신선식품은 GAP, 친환경 등 다양한 라벨 존재하기 때문에 라벨 자체가 브랜드와 유사한 기능을 수행 할 수 있다. 하지만, 유기농 전문점이나 그 외 다른 라벨과 직접적인 비교를 하지 않았기 때문에 추후 연구주제로 남긴다. 키워드: 대형슈퍼마켓, 유기농식품, 만족도, 매장 이미지, 카테고리 매니지먼트 Purpose – The purpose of the study is to explore the relationship among organic food, retailers, and consumer in large scale supermarket. Design/methodology/approach – A conceptual model is developed and tested using multi-regression Findings – The study found that organic label functions very similar as a brand. The organic label satisfaction can be fully mediated from store image, and positively related to the behavioral intentions. However, the organic label satisfaction and store satisfaction do not influence each other. Research implication/limitations – The result tells that organic food shopping motives are different in supermarket over specialty formats, and organic label functions as a brand. Those will be future subjects to develop. Practical implication – The findings provide new insights for organic food category management for supermarket retailers. Since the organic food satisfaction does not have a positive influence on the store satisfaction, large supermarkets can consider removing the separate space or shelf of the organic food which it costs, but consider minimizing the space of the organic food SKU. In addition, organic food manufactures must be aware that not all retailers or channels can be relevant to selling organic foods. The manufactures need to understand the store image of each large supermarket first and start creating sourcing strategy. Key word: Retailing, Organic Food, Satisfaction, Store Image

      • Antityrosinase compounds from Roots of Sophora flavescens and hips of Rosa rugosa

        sandesh sancheti Kongju National University 2008 국내석사

        RANK : 232975

        Bioassay-directed fractionation of the extract of roots of Sophora flavescens led to the isolation of flavonoid kuraridinol (1). The structure of isolated compound was identified on the basis of NMR and MS analysis and by direct comparison with that of reported. Compound 1 displayed significant tyrosinase inhibitory and antioxidant activities with IC_(50) values 96 ㎍/ml and 79 ㎍/ml, respectively. Hips of Rosa rugosa led to the isolation of unknown compound (2). The structure of isolated compound was identified on the basis of NMR and MS analysis. Compound 2 displayed significant tyrosinase inhibition with 80 %.

      • (A) study on the fabrication process optimization of vacuum insulation glazing using microwave

        김재경 Kongju National University 2019 국내박사

        RANK : 232975

        The Republic of Korea is the world's 10th highest energy-consuming country, and there are circumstances in which measures to reduce energy consumption are urgent. The energy consumed in buildings account for approximately 24.5% of the national consumption, and especially for energy applications, heating accounts for the largest proportion. Therefore, one of the important measures is reducing the heat loss inside buildings for energy consumption reduction. Windows are made of glass and frames, and the thermal insulation performance of windows is most affected by the glass, so the important technology of high-insulation windows is insulated glass. Accordingly, development of vacuum glazing similar to a wall is urgently required in terms of energy conservation of the building, as well as energy savings in the whole country. The vacuum-insulated glazing panel is a heat-insulating material that can be used to reduce the energy losses generated through the windows of buildings by maintaining a gap between two panes of glass and sealing the edges to maintain a vacuum inside. The main processes of vacuum glazing can be roughly divided into three steps: a pillar placing step to maintain the interval between the two panes, a step to seal the edges of the two panes, and exhausting the inside of the glass and sealing. Research on each process has been actively conducted. The edge-sealing process is an important process for maintaining the vacuum state of the vacuum glazing, and because the vacuum state is maintained, high reliability is required. In this study, using screen printing for vacuum-glazing fabrication, a vacuum gap holding pillar was printed and the edges of the glass were sealed using microwaves in a chamber. We optimized the screen-printing process parameters in order to arrange the cross-sectional shape of the screen pillar to be close to a trapezoid to maintain the vacuum gap. Through basic experiments, we derived the main process conditions affecting the pillar shape, and formulated an experimental plan of four factors and three levels using an orthogonal array table. Experiment and analysis of screen printing using the Taguchi experimental design method and regression analysis and were carried out twice, and a total of 18 experiments were conducted. Regression analysis was carried out to derive a regression equation, and its validity was verified through variance analysis and verification experiments. Statistical analysis was carried out using the Weibull distribution by carrying out the ring-on-ring strength test to analyze the strength characteristics according to the placement interval of pillars arranged by screen printing. Considering the strength and safety factor of the characteristic corresponding to the Weibull distribution scale parameter and destruction probability, the strength did not decrease compared with the glass in which the placement intervals of the pillars arranged on the 3[㎜] glass were not arranged. This proved that the limitation of the placement interval is appropriate. We performed electric-thermal coupled analysis using ANSYS. We performed microwave chamber fabrication and edge sealing experiments of glass. In order to ensure the uniformity of the electric field distribution in the microwave chamber, the electric field and temperature distribution according to the waveguide pattern were analyzed. In addition, the electric field and the temperature distribution were analyzed by including carbon plates(susceptor). Based on the results of the simulation, a microwave heating chamber was fabricated and a basic experiment for heating the glass was carried out. Through basic experiments, the main process conditions for edge sealing of glass were derived, and the experimental plan and analysis were carried out using the Box-Behnken method of response-surface analysis based on 3 factors and 3 levels. As the response variable, we set whether or not to seal with reference to the step due to pressure at the edge of glass and optimize the process to minimize the step height to prevent breakage of glass due to step height. A predictable regression equation was derived for the step height of edge sealing and performed the main-effect analysis was performed for the step height. Using the response-optimization tool, we derived the optimum process condition that minimizes the step height of the edge sealing.

      • (The) study of bilingual learning of mathematics at international high school in South Korea

        공미나 Kongju National University 2017 국내석사

        RANK : 232975

        이 연구에서는 한국의 일반 고등학교와는 다르게 이중언어로 수학을 가르치고 있는 한국의 국제학교에서 학생들이 이차함수와 그래프 단원을 중심으로 한국어와 영어로 학습하였을 때의 실태와 성향에 어떤 특징이 보이는지 조사하였다. 이 때 고등학교 1학년 학생들을 대상으로 국내 고1 교육과정을 따른 수학Ⅰ 수업을 한국어로 진행하였고 미국 Common Core State Standard을 따른 Algebra Ⅱ 수업을 영어로 진행하였다. 학생들의 학습 태도 및 수학적 성향과 특징을 살펴보기 위하여 학생 분석, 사전 검사, 설문지 및 인터뷰, 수업 관찰, 단원평가를 통해 이중 언어를 활용한 수학 수업의 실태를 조사하였다. 또한 이중 언어로 진행한 수학수업의 그 장점과 단점을 분석하여 효과성과 두 언어의 선호도를 알아보았다. 국제학교에서 이중언어 수학 학습은 서로 다른 두 언어와 교육과정으로 진행되어 학생들의 학습결손을 보완하고, 수학학습의 어려움을 완화하는데 도움을 주었다. 학생들은 기존의 학습과 영어로 이루어지는 학습이 병행되는 새로운 방식의 학습에서 수학에 흥미를 느꼈고, 수학뿐만이 아니라 영어학습에 대한 동기부여도 가지게 되었다. 마지막으로 이중 언어를 활용한 수학 학습이 한국 학생들의 수학 학습능력 향상과 수학 학습 태도변화에 미치는 영향 및 결과들을 분석하여 수학교육을 활성화 시킬 수 있는 하나의 방안을 제안해 본다.

      • Regulation mechanism for the photomovement in a freshwater green alga, Spirogyra varians

        이지웅 Kongju National University 2018 국내박사

        RANK : 232975

        식물의 광반응 운동은 빛의 조건에 따라 광합성 효율을 높이기 위해 발달된 생리적 반응이다. 식물은 광수용체를 통해 빛의 세기와 방향을 인지하고 광반응 운동을 조절한다. 각 광수용체는 특정 파장의 빛을 흡수할 수 있으며 서로 다른 신호전달 경로를 갖는다. 고등식물의 광반응 운동은 청색광 수용체 phototropin에 의해 조절된다. 조류를 포함하는 민꽃식물 (cryptogam)에서는 적색/원적색광 수용체 phytochrome과 neochrome도 광반응 운동에 관여한다. 녹조식물 해캄은 사상체가 서로 뭉치고 빛 방향으로 이동하는 복잡한 광반응 운동을 한다. 이전 연구에서 이와 같은 해캄의 운동은 각 단색광에 따라 다르게 반응하였다. 본 연구에서는 해캄 (Spirogyra varians)의 각 단색광에 따른 광반응 운동의 분석과 저해 실험을 수행하였으며 광수용체의 분리 및 분석을 통해 운동 조절기작을 규명하였다. 해캄의 사상체는 청색광에서 양성굴광성을 보인 반면 적색광에서는 불규칙적으로 구부러지는 운동을 보였다. 적색광에서 구부러진 사상체는 원적색광에서 빠르게 펴져 phytochrome의 가역적 조절이 예상되었다. Phototropin 신호 전달 요소로 알려진 phosphoinositide 3-kinase를 wortmannin과 LY294002를 통해 저해하였을 때 해캄의 청색광 운동은 저해되었지만 적색광 운동은 영향을 받지 않았다. 세포 내 칼슘 신호 저해제인 caffeine을 처리하였을 때에도 청색광 운동은 저해되었지만 적색광 운동은 영향을 받지 않았다. 세포골격에 대한 저해실험에서 microfilament 저해제인 cytochalasin D와 microtubule 저해제인 oryzalin을 동시에 처리하였을 때 청색광 운동이 저해되었다. 적색광 운동은 cytochalasin D에 영향을 받지 않았지만 oryzalin 처리를 통해 저해되었다. 원적색광에서 관찰된 사상체가 펴지는 운동은 mannitol과 sorbitol을 이용한 삼투압 조절을 통해 저해되었다. 해캄의 각 광반응 운동에 관여할 것으로 판단되는 phototropin과 phytochrome을 분리 및 분석하였다. 해캄의 phototropin은 2 개의 상동유전자를 분리하였으며 SvPHOTA와 SvPHOTB로 명명하였다. 각 phototropin은 모두 light–oxygen–voltage domain과 kinase domain으로 구성된 전형적인 phototropin 구조를 보였지만 분자계통분석에서 서로 다른 분기군에 속하였다. 또한 빛 조건에 따른 유전자 발현 분석과 애기장대를 이용한 형질전환 실험에서 유의한 차이를 보여 기능적 분화가 예상되었다. 해캄의 phytochrome은 canonical phytochrome인 SvPHY1과 SvPHY2 그리고 non-canonical phytochrome인 SvPHYX2을 분리하였으며 분자계통분석에서 윤조식물의 각 분기군에 속하였다. 해캄의 phytochrome은 별해캄목 조류에서 보고되지 않은 PHY1을 보유하고 PHYX1이 결핍된 특이한 구성을 보였다. 해캄 phytochrome의 신호 전달에 관여할 수 있는 FHY1, COP1, HY5, PIF-like가 해캄의 발현유전체에 보존되어 있었으며 적색광과 원적색광에 따른 발현 변화를 보였다. 이상의 결과는 해캄의 광수용체인 phototropin과 phytochrome이 서로 다른 신호 전달 경로와 기계적 반응기 (mechanical effector)를 이용하여 각 단색광 운동을 조절한다는 것을 의미하였다. 해캄 사상체에서 관찰되는 복잡한 광반응 운동은 광수용체들의 상보적인 운동 조절의 결과로 판단된다. Plants and freshwater algae devoid of flagella evolved various photomovements to optimize their photosynthetic efficiency. The filaments of Spirogyra varians exhibit complex photomovement and form a compact mat which enables them to adjust their light exposure. In monochromatic lights, the S. varians filaments formed bundles and showed rapid undulating movement under blue light, while formed loose mat without distinct movement under red light. Photomovement of filament fragments (1–10 cells) was analyzed using various photoreceptor signaling component and cytoskeleton inhibitors under monochromatic light. Different patterns of movement were observed under blue and red light. The filaments showed positive phototropism under blue light. Under red light, the filaments bent to irregular shape, but rapidly became unbent by exposure to far-red light suggesting the involvement of phytochrome in this movement. The mechanical effector for the red-light response was microtubule; the movement was inhibited effectively by the microtubule inhibitor, oryzalin. The blue-light movement was partially inhibited by the single treatment of either cytochalasin D or oryzalin, but was completely blocked when both chemicals were applied together. Phototropin-signaling inhibitors, wortmannin and LY294002, reversibly inhibited the blue-light movement. Calcium signaling inhibitor, caffeine treatment reversibly stopped the blue-light movement, while the red-light movement was not affected by calcium inhibitors. To decipher the genetic control of blue light-induced photomovement, two phototropin homologues were isolated from S. varians, and named SvPHOTA and SvPHOTB. Both phototropins have similar molecular structure consisted of two light–oxygen–voltage domains (LOV1, LOV2) and a serine/threonine kinase domain. SvPHOTA and SvPHOTB had 48.7% sequence identity. Phylogenetic analysis showed SvPHOTA and SvPHOTB belong to different clades suggesting early divergence, possibly before the divergence of land plants from the Zygnematales. qPCR and northern blot analysis showed that SvPHOTA and SvPHOTB responded differently to red and blue light. SvPHOTA was consistently expressed in the dark and in blue light, while SvPHOTB was expressed only when the plants were exposed to light. When the filaments were exposed to red light, SvPHOTA was significantly downregulated whereas SvPHOTB was highly upregulated. When SvPHOTA was incorporated into the phot1-5 phot2-3 double mutant of Arabidopsis thaliana the phototropin-mediated responses including chloroplast accumulation and leaf flattening were restored, while SvPHOTB transgenic plant did not exhibit any significant restored responses. The red/far-red light reversible photomovement, which is expected to involvement of phytochrome, was observed using whole filaments of S. varians. The filaments slowly bent and aggregated to form a tangled mass in red light. In far-red light, the filaments unbent, stretched rapidly and separated from each other. Mannitol and sorbitol treatment significantly inhibited this far-red light movement suggesting that turgor pressure is the driving force of this movement. The bending and aggregating movement of filaments in red light were not affected by osmotic change. Three phytochrome homologues isolated from S. varians showed unique phylogenetic characteristics. Two canonical phytochromes were named as SvPHY1 and SvPHY2, and a non-canonical phytochrome as SvPHYX2. SvPHY1 is the first PHY1 family phytochrome reported in zygnematalean algae. The genes involved in the transport of phytochromes into the nucleus and following transcriptional regulation factors were characterized, and their expression was significantly changed in response to red and far-red light. These results suggest that the complex photomovement of S. varians is the results of a two-track control of mechanical effectors signaled by the combination of phototropin and phytochrome. Although the pattern of photomovement in S. varians is unique the downstream signaling process of each photoreceptor was similar to that of higher plant. The structure and function of photoreceptors were well conserved, and most genes involved in downstream signalling were also identified in S. varians.

      • Regulation of differentiation and inflammation on rabbit articular chondrocytes via the Mitogen-Activated Protein Kinases (MAPKs) pathway

        어성희 Kongju National University 2018 국내박사

        RANK : 232975

        관절염은 사람들의 거동을 불편하게하는 주요 원인으로 골관절염(퇴행성 관절염), 류마티스성 관절염, 건선성 관절염으로 구분된다. 본 연구에서는 토끼 관절연골세포에서 PEP-1-SIRT2, 로즈마리산, 올레아놀릭산, IS526캘러스 추출물을 처리하여 연골세포의 분화와 염증 반응에 미치는 효과를 연구하였으며, 이 과정 중 어떠한 신호전달 기전에 의하여 분화와 염증반응이 조절되는지 알아보고자 하였다. 특히, 세포주기의 증식, 분화, 성장, 염증반응 등의 과정에 mitogen-activated protein kinase (MAPKs) 신호경로가 매우 중요하게 작용하는 것에 기반하여 그 조절 기전을 파악하고자하였다. 토끼 관절연골세포의 일차 배양 후 시약을 처리한 후, western blot 면역 화학분석법을 이용하여 type II collagen, SOX-9, COX-2, MMP-1/-13, 신호전달 단백질(ERK-1/-2, p38, JNK)의 발현 및 활성을 분석하였다. Alcian blue 염색을 통해 세포외 기질 분자인 sulfated proteoglycan 생성량을 확인하였으며, PGE2 분석을 통해 염증 매개체인 PGE2양을 측정하였다. 세포 면역 형광염색법과 조직 화학염색법을 통하여 세포 수준과 조직 수준에서의 단백질 발현양 변화를 확인하였다. PEP-1-SIRT2는 연골세포에서 ERK-1/-2 신호경로를 통해 MMPs (MMP-1/-13)을 증가시켜 분화 표지 단백질인 type II collagen 발현을 억제시켰으며, ERK-1/-2와 p38 키나아제 신호경로를 통해 염증반응 단백질인 COX-2의 발현과 PGE2 양을 조절하여 염증반응을 유도하였다. 로즈마리산은 p38 키나아제 신호경로를 통해 MMP-13의 발현을 감소시키면서 type II collagen의 발현을 증가시켜 분화를 유도하였으며, ERK-1/-2 신호경로를 통해 COX-2의 발현과 PGE2 양을 조절하여 염증반응을 유도하였다. 올레아놀릭산은 p38 키나아제 신호경로를 통해 type II collagen 발현을 감소시켜 탈분화를 유도하였으며, ERK-1/-2와 p38 키나아제 신호경로를 통해 COX-2의 발현과 PGE2 양을 조절하여 염증반응을 유도함을 확인하였다. IS526 캘러스 추출물이 유도하는 탈분화와 염증반응을 확인 할 수 있었다. IS526 캘러스 추출물은 ERK-1/-2 신호경로를 통해 MMP-13의 발현을 증가시켰으며, type II collagen의 발현을 감소시켰다. 또한 ERK-1/-2와 p38 키나아제 경로를 통해 COX-2 발현을 조절함으로써 염증반응을 유도하였다. 결론적으로 활성화된 ERK-1/-2와 p38키나아제는 연골세포의 분화를 조절하고 염증반응을 유도하는데 관여하므로 본 연구를 바탕으로 MAPKs 신호경로를 적절히 이용한다면 관절염 환자의 치료에 도움이 될 것으로 사료된다. Background: Osteoarthritis (OA) is a joint disease in which cartilage degradation is the central pathological change. In this study, I investigated the dediffrenetiation and inflammation effects of PEP-1-SIRT2, Rosmarinic acid (Ros.A) and Oleanolic acid in rabbit articular chondrocytes. Methods: ln the current study, primary articular chondrocytes were cultured from rabbit articular cartilage. Western blotting and immunofluorescence were performed to evaluate the expression of type II collagagen and cyclooxygenase-2 (COX-2) and Matrix metalloproteinases (MMPs). In addition, sulfated proteoglycan synthesis and PGE2 production detected by alcian blue staning and PGE2 assay, respectively. The mitogen-activated protein kinases (MAPKs) signaling pathway was also analyzed by Western blotting. Results: The first issue, I confirmed that PEP-1-SIRT2 induced dedifferentiation by measuring the loss of type II collagen and the reduction in chondroitin sulfate proteoglycan levels. PEP-1-SIRT2 also caused inflammation by inducing the expression of COX-2 and prostaglandin E2 (PGE2). In addition, after treatment with PEP-1-SIRT2, increased MMP-1 and -13 expression. Furthermore, PEP-1-SIRT2 caused phosphorylation of both p38 kinase and ERK-1/-2 was observed. The second issu, I found that in rabbit articular chondrocytes, Ros.A increased type II collagen, sulfated-proteoglycan, COX-2, and PGE2 production in a dose- and time- dependent manner. Furthermore, Ros.A suppressed the expression of MMP-13. In addition, treatment with Ros.A activated ERK-1/-2 and p38 kinase signaling pathways. The third issue, oleanolic acid promoted dedifferentiation of chondrocytes by inhibiting type II collagen and pro-inflammatory activity by increasing COX-2 expression. Furthermore, oleanolic acid increased phosphorylation of p38 kinase and down-regulated phosphorylation of ERK-1/-2 was observed. The last issue, IS562-induced a loss of type II collagen and decreased sulfate proteoglycan levels in a dose- and time-dependent manner. In addition, IS526 caused cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-13 and PGE2 production. Phosphorylation of ERK and p38 kinase were increased by IS526. Pharmacological inhibition of MMP-13 blocked the IS526-induced decrease in type II collagen level but COX-2 and PGE2 production were unchanged. Moreover, the inhibition of ERK-1/-2, and p38 kinase with PD98059 (PD), SB203580 (SB) suppressed IS526-induced COX-2 expression. Treatment with SB enhanced the suppression of type II collagen but PD rescued IS526-induced dedifferentiation. Conclusions: These results suggest that PEP-1-SIRT2 promotes MMPs (MMP-1/-13)-induced dedifferentiation via ERK-1/-2 signaling in articular chondrocytes. PEP-1-SIRT2 resgulates COX-2 expression via p38 kinase pathway. Also, ERK-1/-2 regulates Ros.A-induced inflammation and that p38 kinase regulates differentiation by inhibiting MMP-13 in rabbit articular chondrocytes. Oleanolic acid induces loss of type II collagen expression via the p38 kinases pathway and induces inflammation through the p38 kinase and ERK-1/-2 pathways in rabbit articular chondrocytes. Finally, IS526 regulation of type II collagen, MMP-13 and COX-2 expression via the MAPKs pathways in rabbit articular chondrocytes.

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