• Title/Summary/Keyword: c-raf

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Effect of Alkyl Ketene Dimer(AKD) on Red Algae Reinforced Biocomposites (AKD 처리한 홍조류섬유 보강 바이오복합재료의 특성)

  • Lee, Min-Woo;Park, Dong-Hui;Seo, Yung-Bum
    • Journal of Korea Technical Association of The Pulp and Paper Industry
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    • v.43 no.2
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    • pp.66-71
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    • 2011
  • Biocomposites were fabricated with biodegradable polymers and natural fibers. Biocomposites have benefits of low cost, low density, and biodegradability over inorganic fiber composite, and give comparable strength properties. Hydrophobic polymer used for sizing in paper industry, AKD (Akenyl Keten Dimer), was applied to natural fibers, red algae fibers (RAF) in this study, to make fiber surfaces more compatible to hydrophobic nature of matrix polymers. Composites with RAF, kenaf, glass fibers, and carbon fibers have been fabricated by a compression molding method and their thermo-mechanical properties have been studied. Also, the thermal dimensional stability test was done from at 30 to $100^{\circ}C$. The storage moduli and the thermo-mechanical stabilities of polypropylene and poly lactic acid based biocomposites were improved by reinforcing with the RAF and much more with AKD treated fibers. Dimensional stability of biocomposite was also markedly improved by AKD pretrement on RAF.

Differential Activation of Ras/Raf/MAPK Pathway between Heart and Cerebral Artery in Isoproterenol-induced Cardiac Hypertrophy

  • Kim, Hyun-Ju;Kim, Na-Ri;Joo, Hyun;Youm, Jae-Boum;Park, Won-Sun;Warda, Mohamed;Kang, Sung-Hyun;Thu, Vu-Thi;Khoa, Tran-Minh;Han, Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.9 no.5
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    • pp.299-304
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    • 2005
  • Cardiac hypertrophy contributes an increased risk to major cerebrovascular events. However, the molecular mechanisms underlying cerebrovascular dysfunction during cardiac hypertrophy have not yet been characterized. In the present study, we examined the molecular mechanism of isoproterenol (ISO)-evoked activation of Ras/Raf/MAPK pathways as well as PKA activity in cerebral artery of rabbits, and we also studied whether the activations of these signaling pathways were altered in cerebral artery, during ISO-induced cardiac hypertrophy compared to heart itself. The results show that the mRNA level of c-fos (not c-jun and c-myc) in heart and these genes in cerebral artery were considerably increased during cardiac hypertrophy. These results that the PKA activity and activations of Ras/Raf/ERK cascade as well as c-fos expression in rabbit heart during cardiac hypertrophy were consistent with previous reports. Interestingly, however, we also showed a novel finding that the decreased PKA activity might have differential effects on Ras and Raf expression in cerebral artery during cardiac hypertrophy. In conclusion, there are differences in molecular mechanisms between heart and cerebral artery during cardiac hypertrophy when stimulated with β2 adrenoreceptor (AR), suggesting a possible mechanism underlying cerebrovascular dysfunction during cardiac hypertrophy.

Effect of Dangguibohyultang and its combinations on apoptosis in human colorectal adenocarcinoma HCT116 cells (당귀보혈탕(當歸補血湯)의 배합비율에 따른 대장암 세포주 HCT116의 세포사멸 효과)

  • Kim, Byung-Wan;Yun, Hyun-Joung;Jeon, Hyeon-Suk;Yun, Hyung-Joong;Kim, Chang-Hyun;Park, Sun-Dong
    • The Korea Journal of Herbology
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    • v.21 no.2
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    • pp.37-46
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    • 2006
  • Objectives : The purpose of this study was to investigate the effect of Dangguibohyultang (DB) and its combination (DB-I; Astragali membraneus BUNGE : Angelica gigas NAKAI=5:1, DB-II; Astragali membraneus BUNGE:Angelica gigas NAKAI=1:1, DB-III; Astragali membraneus BUNGE:Angelica gigas NAKAI=1:5,) on apoptosis in human colorectal adenocarcinoma HCT116 cells. Methods : To study the cytotoxic effect of methanol extract of DB-I, DB-II and DB-III on HCT116 cells, the cell viability was determined by XTT reduction method and ttypan blue exclusion assay. To confirm the induction of apoptosis, the cleavage of poly ADP-ribose polymerase (PARP), a substrate for caspase-3 and a typical sign of apoptosis, and the activation of procaspase-3, -8 and -9 were examined by western blot analysis. Furthermore, DB-induced apoptosis was confirmed by DNA fragmentation. The release of cytochrome C from mitochondria to cytosol, the level of Bcl-2 and Bax, and the expressions of Raf/MEK/ERK were examined by western blot analysis. Results : DB-I and DB-II reduced proliferation of HCT116 cells in a dose-dependent manner. DB-I and DB-II decreased procaspase-3, -8, -9 levels in a dose-dependent manner and induced the clevage of PARP. DB-I and DB-II also triggered the mitochondrial apoptotic signaling by increasing the release of cytochrome C from mitochondria to cytosol, decreasing of anti-apoptotic Bcl-2, and increasing of pro-apoptotic Bax. DB-I and DB-II decreased the activation of Ras/Raf/MEK/ERK cascade in a dose-dependent manner. Conclusion : These results suggest that DB-I and DB-II induce apoptosis via mitochondrial pathway in HCT116 cells. Furthermore, Raf/MEK/ERK cascade is involved in DB-induced apoptosis. These results suggest that DB is potentially useful as a chemotherapeutic agent in human liver cancer.

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Taxonomic studies of tribe Epilobieae Endl. (Onagraceae) in Korea based on morphology and seed microstructure (외부형태와 종자의 미세구조에 의한 한국산 바늘꽃족(바늘꽃과)의 분류학적 연구)

  • Lee, Sangryong;Heo, Kyeong-In;Lee, Sangtae;Yoo, Manhee;Kim, Yongseong;Lee, Joon Seon;Kim, Seung-Chul
    • Korean Journal of Plant Taxonomy
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    • v.43 no.3
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    • pp.208-222
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    • 2013
  • In this paper, we conducted the taxonomic study of the tribe Epilobieae Endl. and concluded that a total of nine taxa, including one Chamerion (Raf.) Raf. ex Holub and eight Epilobium L., exist in Korea. Although C. angustifolium subsp. angustifolium has been placed traditionally either in Epilobium or Chamaenerion, it can be clearly distinguished from the species of Epilobium by having alternate leaves, slightly zygomorphic flowers, non-clefted petals, and equal length of 8 stamens, supporting the recognition of genus Chamerion. All but one species of Epilobium, E. platystigmatosum, was investigated for the surface of seeds using scanning electron microscope (SEM). The seed sculpture of Korean Epilobium can be classified into three types, i.e., papillose, reticulate, and ridged. E. ciliatum subsp. ciliatum is the only species Epilobium, which has the ridged seed sculpture. E. amurense subsp. cephalostigma can be distinguished from conspecific E. amurense subsp. amurense based on leaf shape, trichome shape and distribution, size and habit. Both E. fastigiatoramosum and E. palustre have entire leaf margins, but they can be distinguished based on leaf shape, stigma, and seed sculpture; the former has elongated elliptic leaves, capitate stigma, ridged seed sculpture, whereas the latter one has elongated lanceolate leaves, club-shaped stigma, and reticulate seed sculpture. Finally, we report the first record of E. platystigmatosum in Korea, and further comparative study including conspecific populations from Japan and China can clarify the occurrence of this taxon in Korea.

The Study on the Antiallergic Action of Poncirus trifoliata (지실(枳實)의 항알러지 작용에 대한 연구)

  • Kim, Hyeong-Kyun;Lee, Eun-Jeong;Kweon, Yong-Taek;Hwang, Kwang-Ho;Joo, Hong-Hyun;Song, Bong-Keun
    • The Journal of Internal Korean Medicine
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    • v.21 no.1
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    • pp.156-161
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    • 2000
  • The unripe fruit of Poncirus trifoliata Raf has been used for the treatment of allergic disease. Recently it was reported that the fruit inhibits passive cutaneous anaphylaxis and histamine release at mast cell. Type I immediate hypersensitivity of anaphylactic type is caused by released mediate chemical at mast cell. Histamine is also known as one of potent mediate chemical. Also release of mediate chemical is affected by specific stimulation of IgE combined with mast cell. Activation of mast cell is known to be stimulated by compound 48/80 and inhibited by increase of cAMP. In this experiment, the effect of water extract of Poncirus trifoliata Raf fruit (PT) on a histamine release, cAMP concentration and IgE production was measured. Compound 48/80 was administrated to the mouse peritoneal cell which was pretreated with PT. PT dosedependently inhibited histamine release at peritoneal mast cell and the serum level of histamine induced by compound 48/80. PT also instantly increased cAMP level of peritoneal mast cell right after it was added and the level gradually decreased. Production of IgE induced by antigens at mouse peritoneal cell was inhibited by PT. The IgE synthesis is induced by IL-4 and it is known that lipopolysaccharide(LPS) plus IL-4 cause an increase in IgE secretion by murine B cells. The effects of PT inhibited the production of IgE activated by LPS plus IL-4 at human U266B1 cells. These results indicate that PT has antiallergic activity by Inhibition of IgE production from B cells and histamine release by increase of cAMP.

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Multiple Signaling Pathways Contribute to the Thrombin-induced Secretory Phenotype in Vascular Smooth Muscle Cells

  • Jeong, Ji Young;Son, Younghae;Kim, Bo-Young;Eo, Seong-Kug;Rhim, Byung-Yong;Kim, Koanhoi
    • The Korean Journal of Physiology and Pharmacology
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    • v.19 no.6
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    • pp.549-555
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    • 2015
  • We attempted to investigate molecular mechanisms underlying phenotypic change of vascular smooth muscle cells (VSMCs) by determining signaling molecules involved in chemokine production. Treatment of human aortic smooth muscle cells (HAoSMCs) with thrombin resulted not only in elevated transcription of the (C-C motif) ligand 11 (CCL11) gene but also in enhanced secretion of CCL11 protein. Co-treatment of HAoSMCs with GF109230X, an inhibitor of protein kinase C, or GW5074, an inhibitor of Raf-1 kinase, caused inhibition of ERK1/2 phosphorylation and significantly attenuated expression of CCL11 at transcriptional and protein levels induced by thrombin. Both Akt phosphorylation and CCL11 expression induced by thrombin were attenuated in the presence of pertussis toxin (PTX), an inhibitor of Gi protein-coupled receptor, or LY294002, a PI3K inhibitor. In addition, thrombin-induced production of CCL11 was significantly attenuated by pharmacological inhibition of Akt or MEK which phosphorylates ERK1/2. These results indicate that thrombin is likely to promote expression of CCL11 via PKC/Raf-1/ERK1/2 and PTX-sensitive protease-activated receptors /PI3K/Akt pathways in HAoSMCs. We propose that multiple signaling pathways are involved in change of VSMCs to a secretory phenotype.

Increased expression of interleukin-1β in triglyceride-induced macrophage cell death is mediated by p38 MAP kinase

  • Sung, Ho-Joong;Son, Sin-Jee;Yang, Seung-Ju;Rhee, Ki-Jong;Kim, Yoon-Suk
    • BMB Reports
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    • v.45 no.7
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    • pp.414-418
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    • 2012
  • Triglycerides (TG) are implicated in the development of atherosclerosis through formation of foam cells and induction of macrophage cell death. In this study, we report that addition of exogenous TG induced cell death in phorbol 12-myristate 13-acetate-differentiated THP-1 human macrophages. TG treatment induced a dramatic decrease in interleukin-$1{\beta}$ (IL-$1{\beta}$) mRNA expression in a dose- and time-dependent manner. The expression of granulocyte macrophage colony-stimulating factor and platelet endothelial cell adhesion molecule remained unchanged. To identify signaling pathways involved in TG-induced downregulation of IL-$1{\beta}$, we added p38 MAPK, protein kinase C (PKC) or c-Raf1 specific inhibitors. We found that inhibition of p38 MAPK alleviated the TG-induced downregulation of IL-$1{\beta}$, whereas inhibition of PKC and c-Raf1 had no effect. This is the first report showing decreased IL-$1{\beta}$ expression during TG-induced cell death in a human macrophage line. Our results suggest that downregulation of IL-$1{\beta}$ expression by TG-treated macrophages may play a role during atherogenesis.

Bag-1L is a Stress-withstand Molecule Prevents the Downregulation of Mcl-1 and c-Raf Under Control of Heat Shock Proteins in Cisplatin Treated HeLa Cervix Cancer Cells

  • Ozfiliz, Pelin;Arisan, Elif Damla;Coker-Gurkan, Ajda;Obakan, Pinar;Eralp, Tugce Nur;Dinler-Doganay, Gizem;Palavan-Unsal, Narcin
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.11
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    • pp.4475-4482
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    • 2014
  • Background: Cisplatin, a DNA damaging agent, induces apoptosis through increasing DNA fragmentation. However, identification of intrinsic resistance molecules against Cisplatin is vital to estimate the success of therapy. Bag-1 (Bcl-2-associated anthanogene) is one anti-apoptotic protein involved in drug resistance impacting on therapeutic efficiency. Elevated levels of this protein are related with increase cell proliferation rates, motility and also cancer development. For this reason, we aimed to understand the role of Bag-1 expression in Cisplatin-induced apoptosis in HeLa cervix cancer cells. Cisplatin decreased cell viability in time- and dose-dependent manner in wt and Bag-1L+HeLa cells. Although, $10{\mu}M$ Cisplatin treatment induced cell death within 24h by activating caspases in wt cells, Bag-1L stable transfection protected cells against Cisplatin treatment. To assess the potential protective role of Bag-1, we first checked the expression profile of interacting anti-apoptotic partners of Bag-1. We found that forced Bag-1L expression prevented Cisplatin-induced apoptosis through acting on Mcl-1 expression, which was reduced after Cisplatin treatment in wt HeLa cells. This mechanism was also supported by the regulation of heat shock protein (Hsp) family members, Hsp90 and Hsp40, which were involved in the regulation Bag-1 interactome including several anti-apoptotic Bcl-2 family members and c-Raf.

Design and Synthesis of an Anticancer Diarylurea Derivative with Multiple-Kinase Inhibitory Effect

  • El-Gamal, Mohammed I.;Oh, Chang-Hyun
    • Bulletin of the Korean Chemical Society
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    • v.33 no.5
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    • pp.1571-1576
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    • 2012
  • A diarylurea compound 1 possessing pyrrolo[3,2-$c$]pyridine nucleus was designed and synthesized with structure similarity to Sorafenib. Compound 1 was tested over 60-cancer cell line panel at a single dose concentration of 10 ${\mu}M$ and showed high activity. It was further tested in a five-dose mode to determine its $IC_{50}$, TGI, and $LC_{50}$ values over the 60 cell lines. Compound 1 showed high potency and good efficacy, and was accordingly tested at a single dose concentration of 10 ${\mu}M$ over a panel of 40 kinases. At this concentration, it completely inhibited the enzymatic activities of a number of oncogenic kinases, including ABL, ALK, c-RAF, FLT3, KDR, and TrkB. The target compound was subsequently tested over these 6 kinases in 10-dose testing mode in order to determine its $IC_{50}$ values.

Induction of the Nuclear Proto-Oncogene c-fos by the Phorbol Ester TPA and c-H-Ras

  • Kazi, Julhash U.;Soh, Jae-Won
    • Molecules and Cells
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    • v.26 no.5
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    • pp.462-467
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    • 2008
  • TPA is known to cooperate with an activated Ras oncogene in the transformation of rodent fibroblasts, but the biochemical mechanisms responsible for this effect have not been established. In the present study we used c-fos promoter-luciferase constructs as reporters, in transient transfection assays, in NIH3T3 cells to assess the mechanism of this cooperation. We found a marked synergistic interaction between TPA and a transfected v-Ha-ras oncogene in the activation of c-fos promoter and SRE. SRE has binding sites for TCF and SRF. A dominant-negative Ras (ras-N17) inhibited the TPA-Ras synergy by blocking the PKC-MAPK-TCF pathway. Dominant-negative RhoA and Rac1 (but not Cdc42Hs) inhibited the TPA-Ras synergy by blocking the Ras-Rho-SRF signaling pathway. Constitutively active $PKC{\alpha}$ and $PKC{\varepsilon}$ showed synergy with v-Ras. These results suggest that the activation of two distinct pathways such as Ras-Raf-ERK-TCF pathway and Rho-SRF pathway are responsible for the induction of c-fos by TPA and Ras in mitogenic signaling pathways.