• Title/Summary/Keyword: MEK1

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3,4-Dihydroxytoluene suppresses UVB-induced wrinkle formation by inhibiting Raf-1

  • Park, Sang-Hee;Kang, Nam Joo
    • Korean Journal of Food Science and Technology
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    • v.52 no.4
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    • pp.385-395
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    • 2020
  • This study examined the effect of 3,4-dihydroxytoluene (DHT) on UVB-induced photoaging and determined its molecular mechanisms, using HaCaT human keratinocytes and SKH-1 hairless mice. DHT suppressed UVB-induced matrix metalloproteinase-1 (MMP-1) expression in HaCaT cells. In vivo data from mouse skin supported that DHT decreased UVB-induced wrinkle formation, epidermal thickness, and matrix metalloproteinase-13 (MMP-13) expression. DHT appeared to exert its anti-aging effects by suppressing UVB-induced Raf-1 kinase activity and subsequent attenuation of UVB-induced phosphorylation of MEK, ERK, and p90RSK in HaCaT cells. In vitro and in vivo pull-down assays revealed that DHT bound with Raf-1 in ATP-noncompetitive manner. Overall, DHT appears to anti-photoaging effects in vitro and in vivo through the suppression of Raf-1 kinase activity and may have potential as a treatment for the prevention of skin aging.

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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The Intracisternal Administration of MEK Inhibitor Attenuates Mechanical and Cold Allodynia in a Rat Model of Compression of the Trigeminal Ganglion

  • Lee, Min-K.;Yoon, Jeong-H.;Park, Min-K.;Yang, Gwi-Y.;Won, Kyung-A.;Park, Yoon-Yub;Ahn, Dong-K.
    • International Journal of Oral Biology
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    • v.35 no.3
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    • pp.75-81
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    • 2010
  • The present study investigated the role of ERK in the onset of mechanical and cold allodynia in a rat model of compression of the trigeminal ganglion by examining changes in the air-puff thresholds and number of scratches following the intracisternal injection of PD98059, a MEK inhibitor. Male Sprague Dawley rats weighing between 250 and 260 g were used. Under anesthesia, the rats were mounted onto a stereotaxic frame and received 4% agar ($10\;{\mu}l$) solution to compress the trigeminal ganglion. In the control group, the animals were given a sham operation without the application of agar. Changes in behavior were examined at 3 days before and at 3, 7, 10, 14, 17, 21, 24, 30, and 40 days after surgery. Compression of the trigeminal ganglion significantly decreased the air-puff thresholds. Mechanical allodynia was established within 3 days and persisted over postoperative day 24. To evaluate cold allodynia, nociceptive scratching behavior was monitored after acetone application on the vibrissa pad of the rats. Compression of the trigeminal ganglion was found to produce significant cold allodynia, which persisted for more than 40 days after surgery. On postoperative day 14, the intracisternal administration of $1\;{\mu}g$ or $10\;{\mu}g$ of PD98059 in the rat model significantly decreased the air-puff thresholds on both the ipsilateral and contralateral side. The intracisternal administration of $10\;{\mu}g$ of PD98059 also significantly alleviated the cold allodynia, compared with the vehicle-treated group. These results suggest that central ERK plays an important role in the development of mechanical and cold allodynia in rats with compression of the trigeminal ganglion and that a targeted blockade of this pathway is a potential future treatment strategy for trigeminal neuralgia-like nociception.

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.

Involvement of Corticotropin-releasing Factor Receptor 2β in Differentiation of Dopaminergic MN9D Cells

  • Jin, Tae-Eun;Jang, Miae;Kim, Hyunjung;Choi, Yu Mi;Cho, Hana;Chung, Sungkwon;Park, Myoung Kyu
    • Molecules and Cells
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    • v.26 no.3
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    • pp.243-249
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    • 2008
  • Corticotropin releasing factor (CRF) mediates various responses to stress through CRF receptors 1 and 2. CRF receptor 2 has two forms, $2{\alpha}$ and $2{\beta}$ each of which appears to have distinct roles. Here we used dopaminergic neuron-derived MN9D cells to investigate the function of CRF receptor 2 in dopamine neurons. We found that n-butyrate, a histone deacetylase inhibitor, induced MN9D cell differentiation and increased gene expression of all CRF receptors. CRF receptor $2{\beta}$ was minimally expressed in MN9D cells; however, its expression dramatically increased during differentiation. CRF receptor $2{\beta}$ expression levels appeared to correlate with neurite outgrowth, suggesting CRF receptor $2{\beta}$ involvement in neuronal differentiation. To validate this statement, we made a CRF receptor $2{\beta}$-overexpressing $MN9D/CRFR2{\beta}$ stable cell line. This cell line showed robust neurite outgrowth and GAP43 overexpression, together with MEK and ERK activation, suggesting MN9D cell neuronal differentiation. From these results, we conclude that CRF receptor $2{\beta}$ plays an important role in MN9D cell differentiation by activating the MEK/ERK signaling pathway.

Inhibitory Effect of LPS-Induced Plasminogen Activator Inhibitor-1 by Ascofuranone in Rat Kidney Fibroblast Cells (Ascofuranone에 의한 plasminogen activator inhibitor-1 발현저해 효과)

  • Chang, Young-Chae
    • Journal of Life Science
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    • v.19 no.10
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    • pp.1438-1443
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    • 2009
  • Renal fibrosis is a final common manifestation of every type of chronic kidney disease. Plasminogen activator inhibitor (PAI)-1 is induced by lipopolysaccharide (LPS) and is known to play an essential role in the progress of renal fibrosis. In this paper, we found that an isoprenoid antibiotic, ascofuranone (AF), suppresses expression of profibrotic factors, PAI-1 and promoter activity of PAI-1 induced by LPS in rat kidney fibroblast cells. We therefore investigated signaling pathway mediated inhibitory effects of LPS-induced PAI-1 by AF in rNRK-49F cells. PAI-1 expression is suppressed by treatment with kinase inhibitors for MEK-1/2, as it isin inhibition of PAI-1 expression by AF, and AF inhibits phosphorylation of ERK-1/2. This study suggest that AF suppresses expression of PAI-1 through the inhibition of an ERK-1/2-dependent signal transduction pathway. The data indicates the possibility that AF can be used to prevent the development and progression of renal fibrosis.

Involvement of Multiple Signaling Molecules in Peptidoglycan-induced Expression of Interleukin-1α in THP-1 Monocytes/Macrophages (THP-1 단핵구의 펩티도글리칸 유래 인터루킨-1 알파 발현에서 TLR2, PI3K/Akt/mTOR, MAPKs의 역할)

  • Heo, Weon;Son, Yonghae;Cho, Hyok-rae;Kim, Koanhoi
    • Journal of Life Science
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    • v.32 no.6
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    • pp.421-429
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    • 2022
  • The expression of interleukin-1α (IL-1α) is elevated in monocytic cells, such as monocytes and macro-phages, within atherosclerotic arteries, yet the cellular molecules involved in cytokine upregulation remain unclear. Because peptidoglycan (PG), a major component of gram-positive bacterial cell walls, is detected within the inflammatory cell-rich regions of atheromatous plaques, it was investigated if PG contributes to IL-1α expression in monocytes/macrophages. Exposure of THP-1 monocytic cells to PG resulted in elevated levels of IL-1α gene transcripts and increased secretion of IL-1α protein. The transcription and secretion of IL-1α were abrogated by OxPAPC, an inhibitor of TLR2/4, but not by polymyxin B that inhibits lipopolysaccharide-induced TLR4 activation. To understand the molecular mechanisms of the inflammatory responses due to bacterial pathogen-associated molecular patterns (PAMPs) in diseased arteries, we attempted to determine the cellular factors involved in the PG-induced upregulation of IL-1α expression. Pharmacological inhibition of cell signaling pathways with LY294002 (a PI3K inhibitor), Akti IV (an inhibitor of Akt activation), rapamycin (an mTOR inhibitor), U0126 (a MEK inhibitor), SB202190 (a p38 MAPK inhibitor), SP6001250 (a JNK inhibitor), and DPI (a NOX inhibitor) also significantly attenuated the PG-mediated expression of IL-1α. These results suggest that PG induces the monocytic or macrophagic expression of IL-1α, thereby contributing to vascular inflammation, via multiple signaling molecules, including TLR2, PI3K/Akt/mTOR, and MAPKs.

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 MEK Inhibitor, PD98059 Blocks the Transactivation, but not the Stabilization or DNA Binding Ability, of Hypoxia-Inducible Factor-1$\alpha$

  • Hur, Eun-Seon;Chang, Keun-Young;Lee, Eun-Jung;Lee, Seung-Ki;Park, Hyun-Sung
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.05a
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    • pp.41-83
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    • 2001
  • Under low oxygen tension, cells increase the transcription of specific genes that are involved in angiogenesis, erythropoiesis and glycolysis. Hypoxia-induced gene expression primarily depends on the stabilization of the subunit of Hypoxia-Inducible Factor-1 (HIF-1), which acts as a heterodimeric transactivator.(omitted)

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