• Title/Summary/Keyword: 억제인자

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THE EFFECT OF PKC PATHWAY & MAPK PATHWAY ON RUNX2 TRANSCRIPTIONAL ACTIVITY (Protein kinase C 및 MAPK pathway가 Runx2의 전사 활성에 미치는 영향)

  • Kim, Eun-Jung;Kim, Hyun-Jung;Ryoo, Hyun-Mo;Kim, Hyun-Jung;Kim, Young-Jin;Nam, Soon-Hyeun
    • Journal of the korean academy of Pediatric Dentistry
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    • v.29 no.3
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    • pp.337-344
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    • 2002
  • Runx2, a Runt-related osteoblast-specific transcription factor, is essential for osteoblast differentiation and function. Runx2 was identified as a key regulator of osteoblast-specific gene expression through its binding to the OSE2 element present in these genes. However, little is known about the signaling mechanism regulating Runx2 activity. This study examines the role of protein kinase C (PKC) pathway and mitogen-activated protein kinase (MAPK) pathway in regulating Runx2 and bone marker genes (osteopontin; OP, osteocalcin; OC). Luciferase assay and Northern blot analysis suggested that the stimulation of PKC by PMA increased transcription activity of Runx2 and bone marker genes (OP and OC) and also increased expression of Runx2. The stimulation of MAPK by okadaic acid increased transcription activity of Runx2 and bone marker genes (OP and OC). Pretreatment with PD98059 (Erk pathway inhibitor) and SB203580 (P38 pathway inhibitor) prior to PMA treatment decreased PMA stimulated Runx2 activity. Together these results indicate that both PKC and MAPKs are involved in the regulation of Runx2 activity and also the stimulation of Runx2 transcriptional activity by the PKC pathway is through activation of MAPK pathway.

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Stability Analysis and Reliability Evaluation of the Pretensioned Soil Nailing System (프리텐션 쏘일네일링 시스템의 안정해석 및 신뢰도 분석)

  • 김홍택;강인규;박사원;고용일;권영호
    • Journal of the Korean Geotechnical Society
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    • v.15 no.2
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    • pp.105-127
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    • 1999
  • Application of the soil nailing method is continuously extended in maintaining stable excavations and slopes. Occasionally, however, ground anchor support system may not be used because of space limitations in urban excavation sites nearby the existing structures. In this case, soil nailing system with relatively short length of nails could be efficiently adopted as an alternative method. The general soil nailing support system, however, may result in excessive deformations particularly in an excavation zone of the existing weak subsoils. Pretensioning the soil nails then, could play important roles in reducing deformations mainly in an upper part of the nailed-soil excavation system as well as improving local stability. In the present study, the analytical procedure and design technique are proposed to evaluate maximum pretension force and stability of the pretensioned soil nailing system. Also proposed are techniques to determine the required thickness of a shotcrete facing and to estimate probability of a failure against the punching shear. The predicted results are compared with the limited measurements obtained from the excavation site constructed by using the pretensioned soil nails. Based on the proposed procedure and technique, effects of the radius of a influence circle and dilatancy angle on the thickness of a shotcrete facing, bonded length and safety factors are analyzed. In addition, effects of the reduction of deformations expected by pretensioning of the soil nails are examined in detail throughout an illustrative example and FLAC$^{2D}$ program analysis.s.

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Induction of Anthocyanin and Betaine by Salinity Stress in Germinating Seeds (발아중인 종자로부터 Salinity Stress에 의해 유도되는 Anthocyanin과 Betaine에 관안 연구)

  • 이인순;문혜연
    • KSBB Journal
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    • v.16 no.4
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    • pp.344-350
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    • 2001
  • The effect of salinity stress of Brassica olearacea and Capsicum annuum were studied at various levels of salinity conditions(Na-gluconate, K-gluconate, NaCl, KCl). The effects of salinity stress were measured by seedling growth rates and secondary metabolites contents of the stressed plants. Each seedling studied on the response of different salinity stress. Seedling growth of Capsicum annuum was inhibited up to 200 mM salt tolerance and Brassica olearacea was inhibited up to 400 mM salt tolerance. The produced anthocyanin was separated to high value from 200 mM NaCl in case of Brassica olearana and 50 mM K-gluconate in case of Capsicum annuum. The BADH activity was very high in Brassica olearacea seedlings treated with 200 mM NaCl and in Capsicum annuum seedlings treated with 100 mM K-gluconate. The BADH activities were increased during the early culture days, it induced betaine synthesis. The salinity stress promoted BADH activiy, subsequently endogenous betaine contents were increased, and it seemed to be secure seedling from salinity stress. The salinity concentration of 200 mM was effective on the inhibition of seed germination and on the increase of proline accumulation in tissue. The inhibition of seedling growth and accumulation of secondary metabolites in seedling were caused osmotic hypersensitivity against salinity stress.

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Inhibitory Effects of Acanthopanax chiisanensis Ethanolic Extracts on FcεRI α Chain Expression (지리 오갈피의 FcεRI α chain 발현 저해 효과)

  • Shim, Sun-Yup;Sung, Chan-Ki;Lee, Sang-Won;Choi, Young-Ju;Kim, Hyeung-Rak;Byun, Dae-Seok
    • Journal of Life Science
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    • v.17 no.11
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    • pp.1511-1516
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    • 2007
  • Basophils and mast cells play an important role in $Fc{\varepsilon}RI-mediated$ allergic reaction as effector cells. We studied the effects of Acanthopanax chiisanensis on $Fc{\varepsilon}RI\;{\alpha}$ chain expression in human basophilic KU812F cells. Ethanol extracts from root and stem of A. chiisanensis were tested for inhibitory effects of $Fc{\varepsilon}RI\;{\alpha}$ chain expression. The cell surface $Fc{\varepsilon}RI\;{\alpha}$ chain expression was examined by flow cytometric analysis. All of the extracts of A. chiisanensis reduced the cell surface $Fc{\varepsilon}RI\;{\alpha}$ chain expression. Furthermore, A. chiisanensis extracts caused a decrease in the level of $Fc{\varepsilon}RI\;{\alpha}$ chain mRNA level and $Fc{\varepsilon}RI-mediated$ histamine release. These results suggest that root and stem extracts of A. chiisanensis play an important role in anti-allergic activity via down-regulation of $Fc{\varepsilon}RI\;{\alpha}$ chain expression and decrease in release of inflammatory mediator such as histamine.

Induction of Apoptosis by Bee Venom in A549 Human Lung Epithelial Cancer Cells through Modulation of Bcl-2 and IAP Family and Activation of Caspases (Bcl-2 및 IAP family의 발현 변화와 caspase 활성을 통한 봉독의 인체폐암세포 apoptosis 유도)

  • Woo, Hyun-Joo;Kim, Hyun-Joong;Hong, Su-Hyun;Hong, Sang-Hoon;Choi, Byung-Tae;Lee, Yong-Tae;Park, Dong-Il;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.17 no.11
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    • pp.1596-1600
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    • 2007
  • Bee venom is used to treat inflammatory diseases in Korean traditional medicine and has been known to inhibit proliferation and induce apoptosis in cancer cells. However, the molecular mechanisms involved in bee venom-induced apoptosis are still uncharacterized in human lung cancer cells. In the present study, we investigated the effects of bee venom on the apoptosis of A549 human lung epithelial cancer cells. Treatment of bee venom inhibited the cell viability and induced apoptosis in a concentration-dependent manner as measured by hemocytometer counts, fluorescence microscopy and flow cytometry analysis. Bee venom-induced apoptosis in A549 cells was associated with a marked inhibition of anti-apoptotic Bcl-2 expression without significant changes in the levels of Bax and Bcl-xL. Bee venom treatment also inhibited the levels of IAP family members such as cIAP-1 and cIAP-2 and induced the proteolytic activation of caspase-3 and caspase-9. Although further studies are needed, the present results suggest that apoptotic signals evoked by bee vemon in A549 cancer cells may converge caspases activation through a down-regulation of Bcl-2 rather than an up-regulation of Bax. These findings provide important insights into the possible molecular mechanisms of the anti-cancer activity of bee vemon in human cancer cells.

Anti-oxidative and Anti-inflammatory Activities of Decaisnea insignis Ethanol Extract (Decaisnea insignis 에탄올 추출물의 항산화 및 항염증 활성)

  • Jin, Kyong-Suk;Lee, Ji Young;Kwon, Hyun Ju;Kim, Byung Woo
    • Journal of Life Science
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    • v.24 no.9
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    • pp.973-980
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    • 2014
  • This study was conducted to explore new nutraceutical resources from the plant kingdom possessing biological activities. To fulfill this purpose, the anti-oxidative and anti-inflammatory activities of Decaisnea insignis ethanol extract (DIEE) were evaluated. First, DIEE possessed potent scavenging activity against 1,1-diphenyl-2-picryl hydrazyl (DPPH), similar to ascorbic acid used as a positive control. Moreover, DIEE inhibited lipopolysaccharide (LPS)- and hydrogen peroxide ($H_2O_2$)-induced reactive oxygen species (ROS) in RAW 264.7 cells. Furthermore, DIEE induced the expression of an anti-oxidative enzyme, heme oxygenase 1 (HO-1), and its upstream transcription factor, nuclear factor-E2-related factor 2 (Nrf2), in a dose-dependent manner. The modulation of the HO-1 and Nrf2 expressions might be regulated by mitogen-activated protein kinases (MAPKs) and their upstream signaling pathways. On the other hand, DIEE suppressed LPS-induced nitric oxide (NO) formation without cytotoxicity. The inhibition of the NO formation was the result of the downregulation of inducible NO synthase (iNOS) by DIEE. The suppression of NO and iNOS by DIEE might be modulated by their upstream transcription factors, nuclear factor ${\kappa}B$ ($NF-{\kappa}B$), and activator protein 1 (AP-1) pathways. Taken together, these results provide important new insights that D. insignis possesses anti-oxidative and anti-inflammatory activities. Therefore, it might be utilized as a promising material in the field of nutraceuticals.

Effect of antibacterial substances produced by probiotic lactic acid bacteria on histamine formation in rennet curd (렌넷 커드 내 히스타민 생성에 관한 프로바이오틱 유산균이 생산한 항균 물질의 영향)

  • Lim, Eun-Seo;Choi, Jae-Suk
    • Korean Journal of Microbiology
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    • v.54 no.2
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    • pp.113-125
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    • 2018
  • Purpose of the present study was to investigate the factors affecting the production of antibacterial substances and histamine in rennet curd prepared by inoculation of histamine-producing lactic acid bacteria (LAB) and probiotic LAB. Probiotic Lactobacillus sakei PIL52 and Lactobacillus plantarum FIL20 produced strong antimicrobial agents against histamine-producing bacteria Lactobacillus brevis LAS129, Enterococcus faecium SBP12, and Enterococcus faecalis SBP58. The lactic acid and crude bacteriocin produced from the probiotic LAB inhibited histamine-producing bacteria in a concentration-dependent manner. As the number of probiotic LAB inoculated for the production of rennet curd increased, the antibacterial activity against histamine-producing bacteria was elevated due to the increased amount of lactic acid and crude bacteriocin in the sample. The growth of probiotic LAB as well as histamine-producing bacteria was inhibited by addition of 10% NaCl, thus the antibacterial substances and histamine contents in rennet curd were significantly lower than those of the control (P < 0.05). Meanwhile, the histamine content was not significantly increased when the rennet curd prepared by mixing probiotic LAB and histamine-producing bacteria was stored at $25^{\circ}C$ for 5 days. However, the amount of histamine detected in the rennet curd was significantly (P < 0.05) increased because the antibacterial activity of the bacteriocin produced by the probiotic LAB was decreased at $20^{\circ}C$ for 20 days.

Paraquat Induced Heme Oxygenase-1 in Dopaminergic Cells (도파민 세포에서 Paraquat에 의한 헴산화효소-1의 유도)

  • Chun Hong Sung
    • KSBB Journal
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    • v.20 no.1 s.90
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    • pp.21-25
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    • 2005
  • Paraquat, a widely used herbicide, has been suggested as a potential risk factor for Parkinson's disease. Heme oxygenase-1(HO-1), a marker for oxidative stress and endoplasmic reticulum(ER) stress, is known to catalyze heme to biliverdin, carbon monoxide and free iron in response to various stimuli. Here we show that paraquat activates HO-1 expression in a time-and dose-dependent manner in substantia nigra(SN) dopaminergic neuronal cells. Activation of Ho-1 by paraquat was regulated primarily at the level of gene transcription. Deletion analysis of the promoter and the 5' distal enhancers, E1 and E2, of the HO-1 gene revealed that the E2 enhancer is a potent inducer of the paraquat-dependent Ho-1 gene expression in dopamninergic neuronal cells. Mutational analysis of the E2 enhacer further demonstrated that the transcription factor activator protein-1(AP-1) plays an important role in mediating paraquat-induced HO-1 gene transcription. Moreover, using specific inhibitors of the mitogen-activated protein kinases(MAPKs), we investigated the role of paraquat and MAPKs for HO-1 gene regulation in dopaminergic cells. The c-Jun N-terminal kinase(JNK) inhibitor SP600125 significantly suppressed the expression of HO-1 by paraquat. All these results demonstrate that induction of HO-1 by paraquat requies the activation of the AP-1 and JNK pathway.

Population Pharmacokinetics of Cyclosporine after Hematopoietic Stem Cell Transplantation in Leukemic Patients (조혈모세포이식을 받은 한국 성인 백혈병환자에서 cyclosporine의 집단약동학 분석)

  • Kim, Seung-Hee;Kim, Kyung-Im;Yun, Hwi-yeol;Kang, Won-Ku;Yoon, Sung-Soo;Shin, Wan-Gyoon;Lee, Hye-Suk;Oh, Jung-Mi
    • Korean Journal of Clinical Pharmacy
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    • v.20 no.1
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    • pp.9-16
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    • 2010
  • Purpose: 본 연구는 한국인 성인 조혈모세포이식환자를 대상으로 경구용 사이클로스포린의 집단약동학 분석을 통하여 사이클로스포린의 약동학적 파라미터에 영향을 미치는 요인 분석을 실시하고자 하였다. Methods: 2000년 12월부터 2006년 8월까지 서울대학교병원에서 동종조혈모세포이식을 받고 면역억제제로 사이클로스포린을 복용한 성인 백혈병환자를 대상으로 후향적으로 자료를 수집하였다. 사이클로스포린의 약동학에 영향을 미치는 인자로는 연령, 성별, 이식 후 날짜, 신기능, 공여자와의 관계, 질병의 종류, 혈중 빌리루빈 농도, 사이클로스포린의 대사를 유도하는 프레드니솔론의 투여량, 헤마토크리트, 사이클로스포린의 대사를 저해하는 약물의 병용여부 등을 검토하였다. 분석은 NONMEM$^{(R)}$ VI 프로그램을 이용하였으며, 변수를 추가하지 않은 기본 모형을 만든 후에 단계적인 요인의 추가와 제거를 통해 최종모형을 제작하였다. Results: 최종 상관 모형은 다음과 같다; CL/F (L/h) = $85.6{\times}e^{(0.646\;{\times}\;HCT/28.9\;+\;0.0464\;{\times}\;Gender)}$. 사이클로스포린의 겉보기 클리어런스는 환자의 성별이 남자일 때 또는 헤마토크릿이 감소할수록 증가하였다. 그 외 파라미터는 다음과 같이 계산되었다; $K_{\alpha}=0.0787\;(h^{-1})$; Q=57.1(L/kg/h); $V_{d-central\;compartment}$=1,100 (L); $V_{d-peripheral\;compartment}$ = 213,000(L). 개체간 편차는 40% 미만이었으며, 개체내 편차를 포함하는 잔차는 24.02%였다. Conclusions: 사이클로스포린의 약동학적 특징과 그 클리어런스에 영향을 끼칠 수 있는 임상적 요인을 이해하는 것은 환자 개개인의 용량과 용법의 결정 및 이상반응 발생의 예방에 유용할 수 있다. 한국인 조혈모세포이식환자에서 사이클로스포린의 약동학에 영향을 미치는 최종 파라미터를 구한 본 연구의 결과는 조혈모세포이식을 받은 한국인 성인환자에서 사이클로스포린의 모니터링 및 용량조절에 유용할 것으로 전망된다.

Short-term Nutrient Enrichment Bioassays (NEBs) by Manipulation of TN:TP Ratios and the Response of Primary Productivity (as Chlorophyll-a) (N:P Ratio 조절에 의한 단기 영양염 첨가 바이오에세이(NEBs) 및 1차 생산력(엽록소-a)의 반응성 테스트)

  • Jeong, Da-Bin;An, Kwang-Guk
    • Korean Journal of Environmental Biology
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    • v.31 no.4
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    • pp.383-392
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    • 2013
  • The objective of this study was to determine the effects of N:P ratio on primary productivity measured as chlorophyll-a (CHL) using the approach of In Situ Nutrient Enrichment Bioassays (NEBs) in Daechung Reservoir. The effects of NEBs on the N:P mass ratios were compared with the field data obtained from monthly-chemical monitoring during 2009~2012. The short-term NEBs showed that the response of primary productivity in the phosphorus spiked treatments (5, 15, 20 and 30 N:P ratios) were greater than the responses in the control (C) and nitrogen spiked treatment (N:P ratio=150, $T_{VI}$). The response in the nitrogen treatment (N:P ratio=150, $T_{VI}$) was less compared to control and all five treatments ($T_I{\sim}T_{VI}$). The outcomes of the NEBs suggest that phosphorus limited the phytoplankton growth and nitrogen addition inhibited the algal growth. In the analysis of nutrients and CHL from the ambient epilimnetic water in Daechung Reservoir, minimum N:P ratios resulted in maximum concentrations of CHL. Overall, our results suggest that the N:P ratio was the key factor in regulating the phytoplankton growth in NEB experiments.