• Title/Summary/Keyword: MEK1/2

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Mitogen-Activated Protein Kinase Signal Transduction in Solid Tumors

  • Lei, Yuan-Yuan;Wang, Wei-Jia;Mei, Jin-Hong;Wang, Chun-Liang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.20
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    • pp.8539-8548
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    • 2014
  • Mitogen-activated protein kinase (MAPK) is an important signaling pathway in living beings in response to extracellular stimuli. There are 5 main subgroups manipulating by a set of sequential actions: ERK(ERK1/ERK2), c-Jun N(JNK/SAPK), p38 MAPK($p38{\alpha}$, $p38{\beta}$, $p38{\gamma}$ and $p38{\delta}$), and ERK3/ERK4/ERK5. When stimulated, factors of upstream or downstream change, and by interacting with each other, these groups have long been recognized to be related to multiple biologic processes such as cell proliferation, differentiation, death, migration, invasion and inflammation. However, once abnormally activated, cancer may occur. Several components of the MAPK network have already been proposed as targets in cancer therapy, such as p38, JNK, ERK, MEK, RAF, RAS, and DUSP1. Among them, alteration of the RAS-RAF-MEK-ERK-MAPK(RAS-MAPK) pathway has frequently been reported in human cancer as a result of abnormal activation of receptor tyrosine kinases or gain-of-function mutations in genes. The reported roles of MAPK signaling in apoptotic cell death are controversial, so that further in-depth investigations are needed to address these controversies. Based on an extensive analysis of published data, the goal of this review is to provide an overview on recent studies about the mechanism of MAP kinases, and how it generates certain tumors, as well as related treatments.

Simulation and Optimization Study on the Pressure Swing Distillation of Methyl ethyl ketone-Water System (Methyl ethyl ketone과 물 이성분계 혼합물의 압력변환 증류공정에 대한 전산모사 및 최적화에 대한 연구)

  • Noh, Sang-Gyun;Rho, Jae-Hyun;Cho, Jung-Ho
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.13 no.8
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    • pp.3764-3773
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    • 2012
  • In this study, modeling and optimization works were completed for the separation of 99.9 mol% of methyl ethyl ketone from water through a pressure-swing distillation process since the azeotropic composition varies very sensitively with the change of system pressure. PRO/II with PROVISION release 9.1 was used for the computer simulation and Wilson activity coefficient model was chosen as a modeling equation. A pressure-swing distillation process can be classified into a low-high pressure columns configuration and a high-low pressure columns configuration. In this work, each configurations were optimized for the minimization of steam consumptions, respectively and were compared.

The two-tiered activation of JNK1 prolongs cell survival prior to induced apoptosis

  • Chun, Kwang-Hoon;Ham, Young-Mi;Park, Joon-Seok;Kim, Dong-Hyun;Lee, Seung-Ki
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.165.3-166
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    • 2003
  • The c-Jun N-terminal kinase (JNK) plays essential roles in apoptosis and cell survival. Because apoptosis is promoted by blocking the MEK kinase1-mediated activation of JNK1, we tested whether JNK1 plays dual roles in apoptosis. We show here that JNK1 activity is differentially up-regulated in a two-tiered fashion by specific mechanisms during taxol- or ginsenoside Rh2-induced apoptosis. The early phase of JNK1 activation, but not apoptosis is prevented by expressing the dominant negative SEK1 mutant. (omitted)

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Anti-corrosion Property of the CNT/PVDF Composite Coating Films for Preventing the Corrosion of the Ground System (접지시스템의 부식 방지를 위한 CNT/PVDF 복합막의 내부식 특성)

  • Lim, Young Taek;Shin, Paik-Kyun;Choi, Sun-Kyu;Lee, Sunwoo
    • Journal of the Korean Institute of Electrical and Electronic Material Engineers
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    • v.27 no.11
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    • pp.736-739
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    • 2014
  • In this paper, we propose a enhanced anti-corrosion property of the ground system by coating the CNT/PVDF composite film on it. Polymer material used for preventing the corrosion of ground system is polyvinylidene fluoride (PVDF), and conducting filler for obtaining conductivity of the composite film is multi-walled carbon nanotubes (MWCNTs). The MWCNTs were dispersed in the organic solvent of methyl ethyl ketone 2-butanone (MEK) with different concentration ratios, and the PVDF was solved in the MEK solvent with constant concentration ratio of 1 wt%. The CNT/PVDF composite solution was perpared by mixing and re-dispersing the CNT solution and the PVDF solution. Finally, the CNT/PVDF composite films were fabricated by the spray coating method using the above composite solution. Electrical conductivity, surface states, and anti-corrosion property of the CNT/PVDF composite films coated on the Cu substrate were evaluated. We found that the CNT/PVDF composite film showed relatively low resistance, hydrophobic surface state, and chemical stability. Consequently, we could improve the anti-corrosion property and maintain the electrical conductivity of the ground system by coating the CNT/PVDF composite film on it.

Comparison between the Charcoal Tube Sampling Method and the Diffusive Sampler, and the Applicability of Diffusive Sampler in the Field (확산형포집기(3M OVM #3500)와 활성탄관의 유기용제 포집농도 비교 및 확산형포집기의 현장 적용 가능성)

  • Jang, Sung Ho;Kim, Hyoung-Ah
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.15 no.3
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    • pp.261-269
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    • 2005
  • To investigate the field applicability of a diffusive sampler (3M OVM #3500, passive sampling method) authors conducted a simultaneous measurement of personal organic solvents exposure in the air of the workplaces by charcoal tube with low volume sampler (active sampling method) and diffusive sampler. Samples were collected and analyzed by NIOSH method ($NMAM^{(R)}$) from thirty-eight workers in 12 factories who work in 6 different processes. Geometric mean (GM) and geometric standard deviation (GSD) were used to describe the result. To compare the results of the two methods, paired t-test was used. According to the manual of the exposure assessment of the mixed organic solvents (Ministry of Labor, Korea), Em was calculated. Simple linear regression was used to evaluate the relationship between the two methods. Results were as follows; 1. Eight different solvents (ethyl acetate, n-hexane, toluene, xylene, acetone, isopropyl alcohol, methyl ethyl ketone (MEK), and methyl isobutyl ketone) were detected simultaneously in the two methods and the concentrations of the personal exposure were lower than 0.5 TLV level. The concentration of the charcoal tube method was higher than that of a diffusive sampler in n-hexane and MEK (p<0.05). 2. Em of the charcoal tube method was higher than that of diffusive sampler method but not significantly different and was lower than the OEL (Occupational Exposure Limit) in all 6 processes. 3. There was a significant correlation between the two methods in low concentrations of the 8 organic solvents (p<0.05). In conclusion, there was no difference in charcoal tube method and diffusive sampler method in low concentrations of some organic solvents, diffusive sampler can be applied to assess the personal monitoring in low level exposure.

Mycobacterium tuberculosis-induced Expression of Interleukin-1 Beta is Mediated Via Protein Kinase C Signaling Pathway

  • Cho, Jang-Eun;Lee, Kyung-Hong;Son, Sin-Jee;Park, Sang-Jung;Lee, Hye-Young;Kim, Yoon-Suk
    • Biomedical Science Letters
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    • v.16 no.2
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    • pp.119-122
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    • 2010
  • Interleukin-1${\beta}$ $(IL-1{\beta})$ is one of the key proinflammatory cytokines and it plays an important role for the antimycobacterial host defense mechanisms. In this study, we examined Mycobacterium tuberculosis (MTB)-stimulated induction of IL-1${\beta}$ and evaluated the associated signal transduction pathways. In PMA-differentiated THP-1 cells, MTB infection increased mRNA expression of IL-$1{\beta}$ in a dose-dependent manner. The expression of IL-1${\beta}$ mRNA began to be induced at 1.5 h after infection, and induced expression of IL-1${\beta}$ was retained for 48 h after MTB infection. The increase in expression of IL-1${\beta}$ caused by MTB was reduced in cells treated with Ro-31-8425 (an inhibitor of PK$C{\alpha}$, ${\beta}I$, ${\beta}II$, ${\gamma}$, ${\varepsilon}$) or PD98059 (an inhibitor of MEK1), meanwhile, pre-treatment with $G\ddot{o}6976$ (an inhibitor of $Ca^{2+}$ dependent PK$C{\alpha}$ and PK$C{\beta}I$) or Rottlerin (an inhibitor of PK$C{\delta}$) has no effect on MTB-induced expression of $IL-1{\beta}$ mRNA. These results show that the expression of $IL-1{\beta}$ mRNA caused by MTB may be mediated via MEK1 and PKC isoforms including PK$C{\beta}II$, $PKC{\gamma}$, or $PKC{\varepsilon}$. Further studies are required to determine whether other PKC isoforms $(PKC {\eta},\;{\theta},\;{\varepsilon},\;and\;{\lambda}/{\iota})$, except $PKC{\delta}$, $PKC{\alpha}$, and $PKC{\beta}I$, are also involved in $IL-1{\beta}$ mRNA expression after mycobacterial infection.

The Sampling Efficiencies of Volatile Organic Compounds(VOCs) to the Diffusive Monitor with Activated Carbon Fiber (활성탄섬유를 이용한 확산포집기의 공기 중 유기용제 포집효율에 관한 연구)

  • Byeon, Sang-Hoon;Park, Cheon-Jae;Oh, Se-Min;Lee, Chang-Ha
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.6 no.2
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    • pp.187-201
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    • 1996
  • This study was to evaluate the efficiency of diffusive monitor using activated carbon fiber(ACF, KF-1500) in measuring airborne organic solvents. The following characteristics were identified and studied as critical to the performance of diffusive monitor; recovery, sampling rate, face velocity, reverse diffusion and storage stability. For the evaluation of the performance of this monitor, MIBK, PCE, toluene were used as organic solvents. In the sampling rate experiments, eight kinds of solvents (n-hexane, MEK, DIBK, MCF, TCE, CB, xylene, cumene) as well as the above solvents were used. The results were as follows: 1. The desorption efficiencies(DE's) of ACF diffusive monitor ranged from 83 % to 101 %. In contrast, those of coconut shell charcoal ranged from 78 % to 102 %. Especially, the DE's of ACF for the polar solvents such as MEK were superior to those of charcoal. 2. Experimental sampling rates on ACF were average 42ml/min(37-46ml/min) for 11 organic solvents at $24{\pm}2^{\circ}C$, $50{\pm}5%RH$. However ideal sampling rates(DA/L) were 33 % higher than experimental sampling rates. 3. The initial response(15~16 min) of the testing monitor was 2 times higher than the actual concentration determined by the reference methods at $24{\pm}2^{\circ}C$, $8{\pm}5%RH$ and $80{\pm}5%RH$. Within 1 hours, the curve reached a linear horizontal line at low humidity condition. But sampling efficiencies decreased with respect to time at high humidity condition. And sampling efficiencies were higher at high humidity condition than low humidity condition for MIBK. 4. At very low velocity (less than 0.02 m/sec), the concentration of ACF diffusive monitor were poorly estimated. But ACF diffusive monitor were not affected at higher velocity(0.2 m/sec-0.6 m/sec). 5. There was no significant reverse diffusion when the ACF monitors were exposed to clean air for 2 hours after being exposed for 2 hours at the level of 1 TLV. 6. There was no significant sample loss during 3 weeks of storage at room temperature and 5 weeks of storage at refrigeration.

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The Inhibitory Effect of Apigenin on the Agonist-Induced Regulation of Vascular Contractility via Calcium Desensitization-Related Pathways

  • Je, Hyun Dong;Kim, Hyeong-Dong;La, Hyen-Oh
    • Biomolecules & Therapeutics
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    • v.22 no.2
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    • pp.100-105
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    • 2014
  • Apigenin, a natural flavonoid found in a variety of vegetables and fruits, has been shown to possess many biological functions. The present study was undertaken to investigate the influence of apigenin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Apigenin significantly relaxed fluoride-, thromboxane $A_2$ mimetic- or phorbol ester-induced vascular contraction, which suggests that apigenin could be an anti-hypertensive that reduces agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, apigenin significantly inhibited fluoride-induced increases in pMYPT1 levels and phorbol ester-induced increases in pERK1/2 levels, which suggests the mechanism involving the inhibition of Rho-kinase and MEK activity and the subsequent phosphorylation of MYPT1 and ERK1/2. This study provides evidence regarding the mechanism underlying the relaxation effect of apigenin on agonist-induced vascular contraction regardless of endothelial function.

Endothelium-Independent Effect of Fisetin on the Agonist-Induced Regulation of Vascular Contractility

  • Je, Hyun Dong;Sohn, Uy Dong;La, Hyen-Oh
    • Biomolecules & Therapeutics
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    • v.24 no.1
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    • pp.57-61
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    • 2016
  • Fisetin, a natural flavonoid found in a variety of vegetables and fruits, has been shown to possess many biological functions. The present study was undertaken to investigate the influence of fisetin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Fisetin significantly relaxed fluoride-, thromboxane $A_2$- or phorbol ester-induced vascular contraction suggesting as a possible anti-hypertensive on the agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, fisetin significantly inhibited fluoride-induced increases in pMYPT1 levels and phorbol ester-induced increases in pERK1/2 levels suggesting the mechanism involving the inhibition of Rho-kinase activity and the subsequent phosphorylation of MYPT1 and MEK activity and the subsequent phosphorylation of ERK1/2. This study provides evidence regarding the mechanism underlying the relaxation effect of fisetin on agonist-induced vascular contraction regardless of endothelial function.