• Title/Summary/Keyword: Raf-1

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4-Hexylresorcinol induced angiogenesis potential in human endothelial cells

  • Kim, Min-Keun;Kim, Seong-Gon;Lee, Suk Keun
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.42
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    • pp.23.1-23.11
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    • 2020
  • Background: 4-Hexylresorcinol (4HR) is able to increase angiogenesis. However, its molecular mechanism in the human endothelial cells has not been clarified. Methods: As endothelial cells are important in angiogenesis, we treated the human umbilical vein endothelial cells (HUVECs) with 4HR and investigated protein expressional changes by immunoprecipitation high-performance liquid chromatography (IP-HPLC) using 96 antisera. Results: Here, we found that 4HR upregulated transforming growth factor-β (TGF-β)/SMAD/vascular endothelial growth factor (VEGF) signaling, RAF-B/ERK and p38 signaling, and M2 macrophage polarization pathways. 4HR also increased expression of caspases and subsequent cellular apoptosis. Mechanistically, 4HR increased TGF-β1 production and subsequent activation of SMADs/VEGFs, RAF-B/ERK and p38 signaling, and M2 macrophage polarization. Conclusion: Collectively, 4HR activates TGF-β/SMAD/VEGF signaling in endothelial cells and induced vascular regeneration and remodeling for wound healing.

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.

RASAL1 Attenuates Gastric Carcinogenesis in Nude Mice by Blocking RAS/ERK Signaling

  • Chen, Hong;Zhao, Ji-Yi;Qian, Xu-Chen;Cheng, Zheng-Yuan;Liu, Yang;Wang, Zhi
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.3
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    • pp.1077-1082
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    • 2015
  • Recent studies have suggested that the RAS protein activator like-1 (RASAL1) functions as a tumor suppressor in vitro and may play an important role in the development of gastric cancer. However, whether or not RASAL1 suppresses tumor growth in vivo remains to be determined. In the present study, we investigated the role of RASAL1 in gastric carcinogenesis using an in vivo xenograft model. A lentiviral RASAL1 expression vector was constructed and utilized to transfect the human poorly differentiated gastric adenocarcinoma cell line, BGC-823. RASAL1 expression levels were verified by quantitative real-time RT-PCR and Western blotting analysis. Then, we established the nude mice xenograft model using BGC-823 cells either over-expressing RASAL1 or normal. After three weeks, the results showed that the over-expression of RASAL1 led to a significant reduction in both tumor volume and weight compared with the other two control groups. Furthermore, in xenograft tissues the increased expression of RASAL1 in BGC-823 cells caused decreased expression of p-ERK1/2, a downstream moleculein the RAS/RAF/MEK/ERK signal pathway. These findings demonstrated that the over-expression of RASAL1 could inhibit the growth of gastric cancer by inactivation of the RAS/RAF/MEK/ERK pathway in vivo. This study indicates that RASAL1 may attenuate gastric carcinogenesis.

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.

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.

The Comparison of Commercial Serum-Free Media for Hanwoo Satellite Cell Proliferation and the Role of Fibroblast Growth Factor 2

  • In-sun Yu;Jungseok Choi;Mina K. Kim;Min Jung Kim
    • Food Science of Animal Resources
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    • v.43 no.6
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    • pp.1017-1030
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    • 2023
  • Fetal bovine serum (FBS), which contains various nutrients, comprises 20% of the growth medium for cell-cultivated meat. However, ethical, cost, and scientific issues, necesitates identification of alternatives. In this study, we investigated commercially manufactured serum-free media capable of culturing Hanwoo satellite cells (HWSCs) to identify constituent proliferation enhancing factors. Six different serum-free media were selected, and the HWSC proliferation rates in these serum-free media were compared with that of control medium supplemented with 20% FBS. Among the six media, cell proliferation rates were higher only in StemFlexTM Medium (SF) and Mesenchymal Stem Cell Growth Medium DXF (MS) than in the control medium. SF and MS contain high fibroblast growth factor 2 (FGF2) concentrations, and we found upregulated FGF2 protein expression in cells cultured in SF or MS. Activation of the fibroblast growth factor receptor 1 (FGFR1)-mediated signaling pathway and stimulation of muscle satellite cell proliferation-related factors were confirmed by the presence of related biomarkers (FGFR1, FRS2, Raf1, ERK, p38, Pax7, and MyoD) as indicated by quantitative polymerase chain reaction, western blotting, and immunocytochemistry. Moreover, PD173074, an FGFR1 inhibitor suppressed cell proliferation in SF and MS and downregulated related biomarkers (FGFR1, FRS2, Raf1, and ERK). The promotion of cell proliferation in SF and MS was therefore attributed to FGF2, which indicates that FGFR1 activation in muscle satellite cells may be a target for improving the efficiency of cell-cultivated meat production.

Study on Dose Rate on the Surface of Cask Packed with Activated Cut-off Pieces from Decommissioned Nuclear Power Plant

  • Park, Kwang Soo;Kim, Hae Woong;Sohn, Hee Dong;Kim, Nam Kyun;Lee, Chung Kyu;Lee, Yun;Lee, Ji Hoon;Hwang, Young Hwan;Lee, Mi Hyun;Lee, Dong Kyu;Jung, Duk Woon
    • Journal of Radiation Protection and Research
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    • v.45 no.4
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    • pp.178-186
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    • 2020
  • Background: Reactor pressure vessel (RV) with internals (RVI) are activated structures by neutron irradiation and volume contaminated wastes. Thus, to develop safe and optimized disposal plan for them at a disposal site, it is important to perform exact activation calculation and evaluate the dose rate on the surface of casks which contain cut-off pieces. Materials and Methods: RV and RVI are subjected to neutron activation calculation via Monte Carlo methodology with MCNP6 and ORIGEN-S program-neutron flux, isotopic specific activity, and gamma spectrum calculation on each component of RV and RVI, and dose rate evaluation with MCNP6. Results and Discussion: Through neutron activation analysis, dose rate is evaluated for the casks containing cut-off pieces produced from decommissioned RV and RVI. For RV cut-off ones, the highest value of dose rate on the surface of cask is 6.97 × 10-1 mSv/hr and 2 m from it is 3.03 × 10-2 mSv/hr. For RVI cut-off ones, on the surface of it is 0.166 × 10-1 mSv/hr and 2 m from it is 1.04 × 10-1 mSv/hr. Dose rates for various RV and RVI cut-off pieces distributed lower than the limit except the one of 2 m from the cask surface of RVI. It needs to adjust contents in cask which carries highly radioactive components in order to decrease thickness of cask. Conclusion: Two types of casks are considered in this paper: box type for very-low-level waste (VLLW) as well as low-level waste (LLW) and cylinder type for intermediate-level waste (ILW). The results will contribute to the development of optimal loading plans for RV and RVI cut-off pieces during the decommissioning of nuclear power plant that can be used to prepare radioactive waste disposal plans for the different types of wastes-ILW, LLW, and VLLW.

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.