• Journal of Ginseng Research
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• v.43 no.4
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• pp.527-538
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• 2019

Background: Ginsenoside Rg1 was shown to exert ligand-independent activation of estrogen receptor (ER) via mitogen-activated protein kinase-mediated pathway. Our study aimed to delineate the mechanisms by which Rg1 activates the rapid ER signaling pathways. Methods: ER-positive human breast cancer MCF-7 cells and ER-negative human embryonic kidney HEK293 cells were treated with Rg1 ($10^{-12}M$, $10^{-8}M$), $17{\beta}$-estradiol ($10^{-8}M$), or vehicle. Immunoprecipitation was conducted to investigate the interactions between signaling protein and ER in MCF-7 cells. To determine the roles of these signaling proteins in the actions of Rg1, small interfering RNA or their inhibitors were applied. Results: Rg1 rapidly induced $ER{\alpha}$ translocation to plasma membrane via caveolin-1 and the formation of signaling complex involving linker protein (Shc), insulin-like growth factor-I receptor, modulator of nongenomic activity of ER (MNAR), $ER{\alpha}$, and cellular nonreceptor tyrosine kinase (c-Src) in MCF-7 cells. The induction of extracellular signal-regulated protein kinase and mitogen-activated protein kinase kinase (MEK) phosphorylation in MCF-7 cells by Rg1 was suppressed by cotreatment with small interfering RNA against these signaling proteins. The stimulatory effects of Rg1 on MEK phosphorylation in these cells were suppressed by both PP2 (Src kinase inhibitor) and AG1478 [epidermal growth factor receptor (EGFR) inhibitor]. In addition, Rg1-induced estrogenic activities, EGFR and MEK phosphorylation in MCF-7 cells were abolished by cotreatment with G15 (G protein-coupled estrogen receptor-1 antagonist). The increase in intracellular cyclic AMP accumulation, but not Ca mobilization, in MCF-7 cells by Rg1 could be abolished by G15. Conclusion: Ginsenoside Rg1 exerted estrogenic actions by rapidly inducing the formation of ER containing signalosome in MCF-7 cells. Additionally, Rg1 could activate EGFR and c-Src ER-independently and exert estrogenic effects via rapid activation of membrane-associated ER and G protein-coupled estrogen receptor.

• 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.

• 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.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.60-66
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• 2002

Aryl hydrocarbons, environmental contaminants accumulate in tissue and pose potential risk in human health. 2,3,7,8-Tertachlorodibenzo-p-dioxin (TCDD) is known as a most potent toxicant among aryl hydrocarbons. TCDD elicits numerous toxic responses in experimental animals and human, including hepatic carcinoma, pulmonary and skin tumor in adult rodents, craniofacial abnormality during mouse embryogenesis, chloracne, reproductive abnormality, immunotoxicity, endocrine effects in exposed humans.(omitted)

• Fire Science and Engineering
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• v.33 no.4
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• pp.9-15
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• 2019

The flash points of DMF based organic solvent mixtures used in the synthetic leather manufacturing process were measured. The test group was composed of seven types of solvent mixtures, which included DMF, toluene, and MEK. Each flash point was tested according to the international standard test methods of KS M 2010. The flash points were then predicted using some prediction models and compared with the measured data. From the analysis results, the binary mixtures with a mole ratio of less than approximately 0.7 showed that the measured values were under 25 ℃. This showed that the expectation for the flammable risk lowering effects due to the mixing of high flash point materials was reduced. In addition, the predicted values were evaluated using the average absolute deviation (A.A.D). The results showed that the Le Chatelier's models had an "A.A.D" of 1.95 ℃ and were the closest to the measured values.

• 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.

• 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.

• Proceedings of the Korean Nuclear Society Conference
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• 1997.10a
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• pp.778-783
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• 1997

원자력 발전소에서의 중대사고시, 고온의 노심 용융물이 원자로 공동으로 떨어지면 노심용융물과 콘크리트간의 반응(MCCI)에 의한 여러가지 현상으로 인해 격납용기의 건전성을 위협할 수 있다. 본 연구에서는 국내 영광원전 3, 4호기에 사용된 공동구조물 콘크리트와 고온용융물간의 반응특성을 실험적으로 살펴보았다. 실험은 유도가열로를 이용한 1차원 장기침식을 모사하기 위한 MEK-S1 실험이다. 실험에서는 유도로의 전원부족으로 용융풀을 형성하지 못하여 장기침식에는 실패하였다. 하지만 약 150$0^{\circ}C$의 고온 SUS 304에 의한 콘크리트의 침식을 확인할 수 있었다. 실험후 분해한 콘크리트 반응시편의 단면은 침식으로 인해 매우 불규칙한 모양을 나타내었으며, 최대침식 깊이는 24mm로 나타났다. 실험중에 발생한 가스의 성분분석 결과에서 H$_2$, $CO_2$, CO 및 $O_2$, $N_2$등의 가스가 발생된 것을 알 수 있었다.

• Biomedical Science Letters
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• v.9 no.2
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• pp.59-65
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• 2003

When cells are exposed to proteotoxic stresses such as heat shock, amino acid analogs, and heavy metals, they increase the synthesis of the heat shock proteins (HSPs) by activating the heat shock transcription factor 1 (HSF1), whose activity is controlled via multiple steps including homotrimerization, nuclear translocation, DNA binding, and hyperphosphorylation. Under unstressed conditions, the HSF1 activity is repressed through its constitutive phosphorylation by glycogen synthase kinase 3$\beta$ (GSK3$\beta$), extracellular regulated kinase 1/2 (ERK1/2), and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). However, the protein kinase (s) responsible for HSF1 hyperphosphorylation and activation is not yet identified. In the present study, we observed that profile of p38 mitogen-activated protein kinase (p38MAPK) activation in response to heat shock was very similar to those of HSF1 hyperphosphorylation and nuclear translocation. Therefore, we investigated whether p38MAPK is involved in the heat shock-induced HSF1 activation and HSP expression. Here we show that the p38MAPK inhibitors, SB202190 and SB203580, but not other inhibitors including the MEK1/2 inhibitor PD98059 and the PI3-K inhibitor LY294002 and wortmannin, suppress HSF1 hyperphosphorylation in response to heat shock and L-azetidine 2-carboxylic acid (Azc), but not to heavy metals. Furthermore, heat shock-induced HSF1-DNA binding and HSP72 expression was specifically prevented by the p38MAPK inhibitors, but not by the MEK1/2 inhibitor and the PI3-K inhibitors. These results suggest that SB202190- and SB203580-sensitive p38MAPK may positively regulate HSP gene regulation in response to heat shock and amino acid analogs.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.2
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• pp.172-180
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• 2007

Among the nuclear medicine imaging methods available today, $H_2^{15}O-PET$ is most widely used by cognitive neuroscientists to examine regional brain function via the measurement of regional cerebral blood flow (rCBF). The short half-life of the radioactively labeled probe, $^{15}O$, often allows repeated measures from the same subjects in many different task conditions. $H_2^{15}O-$ PET, however, has technical limitations relative to other methods of functional neuroimaging, e.g., fMRI, including relatively poor time and spatial resolutions, and, frequently, insufficient statistical power for analysis of individual subjects. However, recent technical developments, such as the 3-D acquisition method provide relatively good image quality with a smaller radioactive dosage, which in turn results in more PET scans from each individual, thus providing sufficient statistical power for the analysis of individual subject's data. Furthermore, the noise free scanner environment $H_2^{15}O$ PET, along with discrete acquisition of data for each task condition, are important advantages of PET over other functional imaging methods regarding studying state-dependent changes in brain activity. This review presents both the limitations and advantages of $^{15}O-PET$, and outlines the design of efficient PET protocols, using examples of recent PET studies both in the normal healthy population, and in the clinical population.