• Title/Summary/Keyword: RAF

Search Result 145, Processing Time 0.023 seconds

Estrogen receptor β stimulates Egr-1 transcription via MEK1/Erk/Elk-1 cascade in C6 glioma cells

  • Kim, Ji-Ha;Jeong, Il-Yeup;Lim, Yoong-Ho;Lee, Young-Han;Shin, Soon-Young
    • BMB Reports
    • /
    • v.44 no.7
    • /
    • pp.452-457
    • /
    • 2011
  • The Egr-1 is an immediate early response gene encoding a transcription factor that functions in the regulation of cell growth, differentiation, and apoptosis. Estrogen has diverse physiological effects, including cellular proliferation and neuroprotection against brain injury. There are two types of estrogen receptors (ERs), $ER{\alpha}$ and $ER{\beta}$. $ER{\alpha}$-induced Egr-1 expression has been extensively studied; however, the role of $ER{\beta}$ is yet not known. In the present study, we investigated whether or not $ER{\beta}$ induces Egr-1 expression in C6 rat glioma cells, which express $ER{\beta}$ but not $ER{\alpha}$. Our results show that $ER{\beta}$ promoted up-regulation of Egr-1 expression via a non-genomic mechanism involving the Raf/MEK1/Erk/Elk-1 signaling cascade.

Screening of Antibacterial Activity Against to Staphylococcus aureus, Listeria monocytogens, Mannhemia haemolytica and Salmonella gallinarum using Different Plant Extracts (다양한 식물들을 이용한 Staphylococcus aureus, Listeria monocytogens, Mannhemia haemolytica 및 Salmonella gallinarum 항균 추출물 탐색)

  • Ham, Young-Joo;Yang, Jin-Ho;Na, Chong-Sam
    • Korean Journal of Organic Agriculture
    • /
    • v.21 no.1
    • /
    • pp.105-113
    • /
    • 2013
  • Antibacterial activity is an important feature for the development of antibiotics alternatives. Plant extract is considered as a promising alternative for organic farming. In this study, a total of 11 plants were extracted using ethanol to determine their antibacterial activities against to Staphylococcus aureus, Listeria monocytogens, Mannheimia haemolytica and Salmonella gallinarum. The synergistic interaction among plant extracts was also investigated. Plants used in this study were Carthamus nctoricus L. (pA), Poncirus trifollata Raf. (pB), Scutellaria balcalensis Georgi (pC) Prunus sargentii (pD), Cucurbita moschata $D_{UCH}$ Leaf (pE), Allium cepa L. peel (pF) Portulaca oleracea L. (pG), Xanthium strumarium L. (pH), Duchesnea chrysantha (pI), Cudrania tricuspidata (pJ) and Juniperus chinensis L. (pK). The pB and pA had the most broad antibacterial spectrum and the highest activity against to Staph. aureus among plant extract, respectively. In the synergistic interaction, the mixtures of pA and pC as well as pA and pF had batter antibacterial activity against to Staph. Aureus compared with other mixtures.

신경성장기전 및 치료제개발

  • 양성일
    • Proceedings of the Korean Society of Applied Pharmacology
    • /
    • 1993.11a
    • /
    • pp.28-33
    • /
    • 1993
  • Regulation of nerve growth factor (NGF)-induced neuronal differentiation by GTPase activating protein(GAP) and its mechanism were investigated in rat pheochromocytoma cell line, PCl2. Overexpression of GAP caused the delay in the onset of neurite outgrowth of PCl2 eel Is in response to NGF. GAP has been known to inhibit p21$\^$ras/, the activated form of which induces neuronal differentiation. Therefore, the activity of p21$\^$ras/ was compared in control cells and cells overexpressing GAP indirectly by measuring the activities of B-Raf and MAP kinase that are known to be positively regulated by p21$\^$ras/. Surprisingly, NGF-induced activities of these two proteins were the same in control eells and GAP-overexpressing cells. Activities of Trk, PLC-r and SMC that act at a site upstream to p21$\^$ras/ in NGF signal transduction pathway were not also affected by GAP overexpression. Interestingly, however, the extent of tyrosine phosphorylation of SNT was found to be remarkably low in cells overexpressing GAP. It has been shown previously that neurotrophins and not mitogens induce SNT tyrosine phosphorylation in PCl2 cells. Thus it is possible that the timing of NGF-induced neuronal differntiation may be in part regulated by SNT and the slower onset of neurite outgrowth in cells overexpressing GAP may be through the inhibition of SNT by GAP.

  • PDF

Contents of Poncirin and Naringin in Fruit of Poncirus Trifoliata according to Different Harvesting Times and Locations for Two Years (2년 동안 지실의 채취시기 및 지역에 따른 Poncirin과 Naringin의 함량)

  • Lee, Sul-Lim;Seo, Chang-Seob;Kim, Jung-Hoon;Shin, Hyeun-Kyoo
    • Korean Journal of Pharmacognosy
    • /
    • v.42 no.2
    • /
    • pp.138-143
    • /
    • 2011
  • A high performance liquid chromatography (HPLC) method was developed for simultaneous determination of two major flavonoid glycosides (poncirin and nanringin) in Poncirus trifoliata Raf. by different harvesting times and locations for two years. A SunFire $C_{18}$ column (4.6 mm${\times}$250 mm, 5 ${\mu}M$) was used at $40^{\circ}C$ for the determination of poncirin and naringin. The mobile phase using gradient flow consisted of two solvent systems. Solvent A was 1.0% (v/v) aqueous acetic acid and solvent B was acetonitrile with 1.0% (v/v) acetic acid. Flow rate was 1.0 mL/min and injection volume was 10 ${\mu}l$. The chromatogram was monitored by photodiode array (PDA) detection at 280 nm for the identification of two flavonoid glycosides in P. trifoliata. The contents of the two components in P. trifoliata ranged from 0.32~13.02%.

COMPASS - New modeling and simulation approach to PWR in-vessel accident progression

  • Podowski, Michael Z.;Podowski, Raf M.;Kim, Dong Ha;Bae, Jun Ho;Son, Dong Gun
    • Nuclear Engineering and Technology
    • /
    • v.51 no.8
    • /
    • pp.1916-1938
    • /
    • 2019
  • The objective of this paper is to discuss the modeling principles of phenomena governing core degradation/melting and in-vessel melt relocation during severe accidents in light water reactors. The proposed modeling approach has been applied in the development of a new accident simulation package, COMPASS (COre Meltdown Progression Accident Simulation Software). COMPASS can be used either as a stand-alone tool to simulate in-vessel meltdown progression up to and including RPV failure, or as a component of an integrated simulation package being developed in Korea for the APR1400 reactor. Interestingly, since the emphasis in the development of COMPASS modeling framework has been on capturing generic mechanistic aspects of accident progression in light water reactors, several parts of the overall model should be useful for future accident studies of other reactor designs, both PWRs and BWRs. The issues discussed in the paper include the overall structure of the model, the rationale behind the formulation of the governing equations and the associated simplifying assumptions, as well as the methodology used to verify both the physical and numerical consistencies of the overall solver. Furthermore, the results of COMPASS validation against two experimental data sets (CORA and PHEBUS) are shown, as well as of the predicted accident progression at TMI-2 reactor.

Inhibition of the Jun Aminoterminal Kinase by SP600125 Blocks PMA-Induced 92kDa Type IV Collagenase Secretion (PMA 유도 제4형 단백분해효소 분비를 차단하는 SP600125에 의한 Jun Aminoterminal Kinase의 억제)

  • Shin, Min
    • Journal of Oral Medicine and Pain
    • /
    • v.26 no.2
    • /
    • pp.95-105
    • /
    • 2001
  • 제 4형 콜라젠을 분해하는 MMP-9은 조직 재생에 중요한 역할을 하기 때문에 주목받아 왔는데, 이전의 문헌들에서 PMA에 의해 이 유전자 발현이 강하게 상승발현된다고 알려져 있다. 비록 MMP-9 발현을 조절하는 PMA의 기전이 잘 밝혀지지는 않았지만, 다른 유전자발현에서의 이 phorbol ester의 효과는 c-raf-1-ERK 신호전달통로의 활성에 관해 연구되어 오고 있다. 하지만 이번 연구에서 저자는 MMP-9 발현에서 PMA의 상승효과에는 대개는 스트레스성 자극과 관련된 JNK1 의존성 신호전달과정이 또한 필요하다는 다른 가능성을 조사하였다. 그 결과 JNK 억제재중 하나인 SP 600125가 UM-SCC-1세포주에서 PMA에 의해 유도된 MMP-9 상승발현을 용량의존적으로 억제하는 것으로 나타났고 72시간동안 전처치를 한 경우에 그의 억제효과가 최대이었다. phorbol ester로 처리한 세포에 GAL4 luciferase reporter와 vector를 주입해서 조사한 결과 PMA가 c-Jun transacting 활성을 상승시켰다. 그뿐 아니라 PMA에 의한 MMP-9 촉진자 활성에는 AP-1 motif가 필요하며 이 motif에 c-Jun이 결합하는 것을 EMSA를 통해 확인하였다. 결론적으로 UM-SCC-1 세포주에서 PMA에 의한 MMP9의 증가된 발현은 이미 밝혀진 ERK 경로뿐 아니라 JNK 경로를 통한 결과임이 밝혀져 이 경로를 차단하는 방법이 또하나의 암치료 방향을 제시해주고 있다.

  • PDF

양자역학으로 π-π interaction 에너지 계산을 통한 ligand binding energy 분석

  • Lee, Seung-Jin;Yun, Ji-Hui;Jang, Seong-Min;Cho, Art E.
    • Proceeding of EDISON Challenge
    • /
    • 2013.04a
    • /
    • pp.89-100
    • /
    • 2013
  • 생물정보학의 다양한 이론적 내용과 계산적 방법들이 갈수록 전문화 되어짐에 따라 신약 개발, 신 물질 합성, 단백질의 구조 예측 등 다양한 분야에서 필요성이 커져가고 있다. 이 중 molecular docking 기술은 단백질과 특정 분자간의 결합 형태를 분자 모델링 기법을 통해 알아내는 방법이며 신약개발 연구에 큰 영향을 미치고 있다. Molecular docking을 통하여 분자간의 결합 형태를 예측하는 과정에서 Protein-ligand complex의 정확한 에너지 측정을 가능하게 하는 scoring function이 필요하다. 그런데 본 연구에서 사용한 B-Raf kinase protein 은 active site 부분에서 ligand와 receptor 간에 aromatic ring로 인한 ${\pi}-{\pi}$ interaction이 정확한 에너지 계산을 어렵게 한다. 이러한 ${\pi}-{\pi}$ interaction 부분의 에너지를 정확하게 계산하기 위해 양자역학 계산을 실시하였다. Active site 부분에서 ligand와 receptor에서 발생하는 각각 다른 5개의 ${\pi}-{\pi}$ interaction 구조를 준비하여 Gaussian을 통해 양자역학 에너지를 계산하였다. 그리고 이러한 결과 값들이 ligand의 활성 값과 어떤 상관관계를 갖는지 살펴보았다. 그 결과 ${\pi}-{\pi}$ interaction을 양자역학으로 계산한 값이 그렇지 않은 것보다 더 좋은 상관관계를 보여주었다. 이는 특별한 구조의 영향으로 ligand와 receptor 간의 결합에너지를 정확하게 계산하기 어려운 문제에서 양자역학을 적용할 경우 더욱 좋은 결과값을 얻을 수 있었다. 또한 이러한 데이터가 신 물질 개발이나 신약 개발 등의 다양한 분야에서 계산화학 방법이 신뢰성을 얻는데 도움 될 수 있다고 생각된다.

  • PDF

Clinical Pearls and Advances in Molecular Researches of Epilepsy-Associated Tumors

  • Phi, Ji Hoon;Kim, Seung-Ki
    • Journal of Korean Neurosurgical Society
    • /
    • v.62 no.3
    • /
    • pp.313-320
    • /
    • 2019
  • Brain tumors are the second most common type of structural brain lesion that causes chronic epilepsy. Patients with low-grade brain tumors often experience chronic drug-resistant epilepsy starting in childhood, which led to the concept of long-term epilepsy-associated tumors (LEATs). Dysembryoplastic neuroepithelial tumor and ganglioglioma are representative LEATs and are characterized by young age of onset, frequent temporal lobe location, benign tumor biology, and chronic epilepsy. Although highly relevant in clinical epileptology, the concept of LEATs has been criticized in the neuro-oncology field. Recent genomic and molecular studies have challenged traditional views on LEATs and low-grade gliomas. Molecular studies have revealed that low-grade gliomas can largely be divided into three groups : LEATs, pediatric-type diffuse low-grade glioma (DLGG; astrocytoma and oligodendroglioma), and adult-type DLGG. There is substantial overlap between conventional LEATs and pediatric-type DLGG in regard to clinical features, histology, and molecular characteristics. LEATs and pediatric-type DLGG are characterized by mutations in BRAF, FGFR1, and MYB/MYBL1, which converge on the RAS-RAF-MAPK pathway. Gene (mutation)-centered classification of epilepsy-associated tumors could provide new insight into these heterogeneous and diverse neoplasms and may lead to novel molecular targeted therapies for epilepsy in the near future.

Inhibitory effect of medicinal plant extracts on xanthine oxidase activity (약용식물 추출물의 xanthine oxidase 활성 저해 효과)

  • Do, Jaeho;Gwak, Jungwon;Rho, Jung Jin;Lee, Kwangseung;Kim, Dong Chung
    • Journal of Applied Biological Chemistry
    • /
    • v.62 no.3
    • /
    • pp.275-280
    • /
    • 2019
  • This study was performed to certify the inhibitory effect of aqueous extracts from sixty-seven medicinal plants on the activity of xanthine oxidase in vitro. Among the sixty-seven medicinal plants, Scutellaria baicalensis Georgi, Citrus aurantium L., Polygonum multiflorum Thunb., Pueraria thunbergiana (Sieb. et Zucc.) Benth., Citrus unshiu Marcor., Rubus coreanus Miquel, Camellia sinensis L., and Poncirus trifoliata Raf. were regarded as effective anti-gout sources. The active substances of P. multiflorum root extract were very stable at pH 2.0 and high temperatures. Xanthine oxidase activity was proportionally inhibited when concentrations of P. multiflorum extract increased. The aqueous extract from P. multiflorum root at a concentration of 2.0 mg/0.1 mL inhibited xanthine oxidase by 73.8%.

The Anti-Cancer Effect of Apamin in Bee-Venom on Melanoma cell line SK-MEL-2 and Inhibitory Effect on the MAP-Kinase Signal Pathway (약침용(藥鍼用) 봉독성분(蜂毒成分) 중(中) Apamin의 항암효과(抗癌效果)와 MAP-Kinase 신호전달체계에 관한 연구(硏究))

  • Kim, Youn-Mi;Lee, Jae-Dong;Park, Dong-Seok
    • Journal of Acupuncture Research
    • /
    • v.18 no.4
    • /
    • pp.101-115
    • /
    • 2001
  • Objective : To characterize the antitumorigenic potential of Apamin, one of the major components of bee venom, its effects on cell proliferation and the mitogen-activated protein kinase (MAPK) signal transduction pathway were characterized using the human melanoma cell line SK-MEL-2. Methods & Results : Cell counting analysis for cell death demonstrated that consistent with a previous results, SK-MEL-2 cells treated with $0.5-2.0{\mu}g/ml$ of Apamin showed no recognizable cytotoxic effect whereas detectable induction of cell death was identified at concentrations over $5.0{\mu}g/ml$. [3H]thymidine incorporation assay for cell proliferation demonstrated that DNA replication of SK-MEL-2 cells is inhibited by Apamin in a dose- and time-dependent manner. To explore whether Apamin-induced growth suppression is associated with the MAPK signaling pathway, phosphorylation of Erk, a function mediator of MAPK growth-stimulating signal, was examined Western blot assay using a phospho-specific Erkl/2 antibody. A significant increase of Erkl/2 phosphorylation level was observed in Apamin-treated cells compared with untreated control cells. Qantitative RT-PCR analysis revealed that Apamin inhibit expression of MAPK downstream genes such as c-Jun, c-Fos, and cyclin D1 but not expression of MAPK pathway component genes including Ha-Ras, c-Raf-1, MEK1, and Erk. Conclusion : It is strongly suggested that the antitumorigenic activity of Apamin might result in part from its inhibitory effect on the MAPK signaling pathway in human melanoma cells SK-MEL-2.

  • PDF