• International Journal of Oral Biology
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• v.35 no.3
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• pp.113-119
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• 2010

Porphyromonas (P.) gingivalis lipopolysaccharide (Pg LPS) is the major pathogenic component of periodontal disease. In this study, we have attempted to determine the expression profiles of the signal transduction pathway genes induced by Pg LPS in comparison with Escherichia (E.) coli LPS (Ec LPS). DC2.4 cells were treated for two hours with $1\;{\mu}g/ml$ of Pg LPS or $0.5\;{\mu}g/ml$ of Ec LPS. The total RNA from these cells was then isolated and reverse-transcribed. Gene expression profiles were then analyzed with a signal transduction pathway finder GEArray Q series kit and significant changes in expression were confirmed by real-time PCR. The microarray results indicated that several genes, including Tnfrsf10b, Vcam1, Scyb9, Trim25, Klk6, and Stra6 were upregulated in the DC2.4 cells in response to Pg LPS treatment, but were downregulated or unaffected by Ec LPS. Realtime PCR revealed that the expression of Trim25, Scyb9 and Tnfrsf10b was increased over the untreated control. Notably, Trim25 and Tnfrsf10b were more strongly induced by Pg LPS than by Ec LPS. These results provide greater insight into the signal transduction pathways that are altered by P. gingivalis LPS.

• Herbal Formula Science
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• v.18 no.2
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• pp.227-239
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• 2010

Objective : The purpose of this study was to develop the simulator which can analyze the anti-inflammatory effects of herbs based on e-cell, or the virtual cell. Method : We have ensured the medical herbs and its active compounds by investigating the oriental medicine records and NBCI(Biomedicine database). Also we have developed the web-based search system for confirming database related to anti-inflammation. We have researched the cell signal pathway related with inflammatory response control and established the mathematical model of herb interaction on selected signal pathway in e-cell. Finally we have developed the prototype which can confirm the result of this model visibly. Results : We constructed the database of 62 cases of anti-inflammatory active compounds in 61 cases of medical herbs which have been known anti-inflammation effects in the paper, 16 cases of inflammatory factors, 10 cases of signal pathways related with inflammatory response and 6,834 cases of URL(Uniform Resource Locator) of referenced papers. And we embodied the web-based research system, which can research this database. User can search basic and detailed information of medical plants related with anti-inflammatory by using information system. And user can acquire information on an active compounds, a signal pathway and a link URL of related paper. Among investigated ten pathways, we selected NF-${\kappa}B$, which plays important role in activation of immune system, and we searched the mechanisms of actions of proteins which could be components of this pathway. We reduced total network into IKK-$I{\kappa}B$ - NF-${\kappa}B$, and completed mathematic modeling by using ordinary differential equations and response variables of $I{\kappa}B-NF-{\kappa}B$ signaling model network which is suggested by Baltimore Group. We designed OED(Ordinary Differential Equation) for response of IKK, $I{\kappa}B$, $NF-{\kappa}B$ in e-cell's cytoplasm and nucleus, and measured whether an active compound of medicinal plants which is inputted by an user would have a anti-inflammation effects in obedience to change in concentration over time. The proposed model was verified by using experimental results of the papers which are listed on NCBI.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.338-348
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• 1997

Background : Endotoxin, the component of outermembrane of gram negative organism, plays an important role in the initiation and amplification of inflammatory reaction by its effects on inflammatory cells. Until recently, there have been continuing efforts to delinate the mechanisms of the signal trasduction pathway of endotoxin stimuli on inflammatory cells. By uncovering the mechanisms of signal transduction pathway of endotoxin stimuli, we can expect to have tools to control the excessive inflammatory responses which sometimes may be fatal to the involved host. It was generally accepted that endotoxin exerts its inflammatory effects through inflammatory cytokines that are produced by endotoxin-stimulated inflammatory cells and there were some reports on the importance of protein kinase C and protein tyrosine kinase activation in the production of inflammatory cytokines by endotoxin So we evaluated the effect of pretreatment of protein kinase C inhibitors (H7, Staurosporin) and protein tyrosine kinase inhibitors(Herbimycin, Genistein) on the endotoxin-stimulated cytokines(IL-8 & TNF-$\alpha$) mRNA expression. Method : Peripheral blood monocytes were isolated from healthy volunteers by Ficoll-Hypaque density gradient method and purified by adhesion to 60mm Petri dishes. Endotoxin(LPS 100ng/ml) was added to each dishes except one control dish, and each endotoxin-stimulated dishes was preincubated with H7, Staurosporin(protein kinase C inhibitor), Herbimycin or Genistein(protein tyrosine kinase inhibitor) respectively except one dish. Four hours later the endotoxin stimulation, total RNA was extracted and Northern blot analysis for IL-8 mRNA and TNF-$\alpha$ mRNA was done. Result : Endotoxin stimulation increased the expression of IL-8 mRNA and TNF-$\alpha$ mRNA expression in human peripheral blood monocyte as expected and the stimulatory effect of endotoxin on TNF-$\alpha$ mRNA expression was inhibited by protein kinase C inhibitors(H7, Staurosporin) and protein tyrosine kinase inhibitors (Herbimycin, Genistein). The inhibitory effect of each drugs was increased with increasing concentration. The stimulatory effect of endotoxin on IL-8 mRNA was also inhibited by H7 and protein tyrosine kinase inhibitors (Herbimycin, Genistein) dose-dependently but not by Staurosporin. Conclusion : Protein kinase C and protein tyrosine kinase are involved in the endotoxin induced signal transduction pathway in human peripheral blood monocyte.

• Journal of Korean Neurosurgical Society
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• v.63 no.4
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• pp.444-454
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• 2020

Objective : Glioblastoma multiforme (GBM) is the most aggressive for of brain tumor and treatment often fails due to the invasion of tumor cells into neighboring healthy brain tissues. Activation of the Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway is essential for normal cellular function including angiogenesis, and has been proposed to have a pivotal role in glioma invasion. This study aimed to determine the dose-dependent effects of ruxolitinib, an inhibitor of JAK, on the interferon (IFN)-I/IFN-α/IFN-β receptor/STAT and IFN-γ/IFN-γ receptor/STAT1 axes of the IFN-receptor-dependent JAK/STAT signaling pathway in glioblastoma invasion and tumorigenesis in U87 glioblastoma tumor spheroids. Methods : We administered three different doses of ruxolitinib (50, 100, and 200 nM) to human U87 glioblastoma spheroids and analyzed the gene expression profiles of IFNs receptors from the JAK/STAT pathway. To evaluate activation of this pathway, we quantified the phosphorylation of JAK and STAT proteins using Western blotting. Results : Quantitative real-time polymerase chain reaction analysis demonstrated that ruxolitinib led to upregulated of the IFN-α and IFN-γ while no change on the hypoxia-inducible factor-1α and vascular endothelial growth factor expression levels. Additionally, we showed that ruxolitinib inhibited phosphorylation of JAK/STAT proteins. The inhibition of IFNs dependent JAK/STAT signaling by ruxolitinib leads to decreases of the U87 cells invasiveness and tumorigenesis. We demonstrate that ruxolitinib may inhibit glioma invasion and tumorigenesis through inhibition of the IFN-induced JAK/STAT signaling pathway. Conclusion : Collectively, our results revealed that ruxolitinib may have therapeutic potential in glioblastomas, possibly by JAK/STAT signaling triggered by IFN-α and IFN-γ.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.2
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• pp.131-138
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• 2009

The binding of interleukin-6 (IL-6) cytokine family ligands to the gp130 receptor complex activates the Janus kinase (JAK)/ signal transducer and activator of transcription 3 (STAT3) signal transduction pathway, where STA T3 plays an important role in cell survival and tumorigenesis. Constitutive activation of STAT3 has been frequently observed in many cancer tissues, and thus, blocking of the gp130 signaling pathway, at the JAK level, might be a useful therapeutic approach for the suppression of STAT3 activity, as anticancer therapy. AG490 is a tyrphostin tyrosine kinase inhibitor that has been extensively used for inhibiting JAK2 in vitro and in vivo. In this study, we demonstrate a novel mechanism associated with AG490 that inhibits the JAK/STAT3 pathway. AG490 induced downregulation of gp130, a common receptor for the IL-6 cytokine family compounds, but not JAK2 or STAT3, within three hours of exposure. The downregulation of gp130 was not caused by enhanced degradation of gp130 or by inhibition of mRNA transcription. It most likely occurred by translation inhibition of gp130 in association with phosphorylation of the eukaryotic initiation factor-2 a. The inhibition of protein synthesis of gp130 by AG490 led to immediate loss of mature gp130 in cell membranes, due to its short half-life, thereby resulting in reduction in the STAT3 response to IL-6. Taken together, these results suggest that AG490 blocks the STAT3 activation pathway via a novel pathway.

• Molecules and Cells
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• v.39 no.3
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• pp.169-178
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• 2016

Although $N{\alpha}$-terminal acetylation (Nt-acetylation) is a pervasive protein modification in eukaryotes, its general functions in a majority of proteins are poorly understood. In 2010, it was discovered that Nt-acetylation creates a specific protein degradation signal that is targeted by a new class of the N-end rule proteolytic system, called the Ac/N-end rule pathway. Here, we review recent advances in our understanding of the mechanism and biological functions of the Ac/N-end rule pathway, and its crosstalk with the Arg/N-end rule pathway (the classical N-end rule pathway).

• International Journal of Oral Biology
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• v.46 no.2
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• pp.81-84
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• 2021

Salivary glands are exocrine glands that secrete saliva into the oral cavity, and secreted saliva plays essential roles in oral health. Therefore, maintaining the salivary glands in an intact state is required for proper production and secretion of saliva. To investigate a specific signaling pathway that might affect the maintenance of mouse submandibular gland (SMGs), RNA sequencing was performed. In SMGs, downregulated expression patterns of Rho-associated protein kinase (ROCK) signaling pathway-related genes, including Rhoa, Rhob, Rhoc, Rock1, and Rock2, were observed. Gene expression profiling analyses of these genes indicate that the ROCK signaling pathway is a potential signal for SMG maintenance.

• International Journal of Stem Cells
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• v.16 no.4
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• pp.376-384
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• 2023

The Wnt 𝛽-catenin signaling pathway is a highly conserved mechanism that plays a critical role from embryonic development and adult stem cell homeostasis. However, dysregulation of the Wnt pathway has been implicated in various diseases, including cancer. Therefore, multiple layers of regulatory mechanisms tightly control the activation and suppression of the Wnt signal. The E3 ubiquitin ligases RNF43 and ZNRF3, which are known negative regulators of the Wnt pathway, are critical component of Wnt signaling regulation. These E3 ubiquitin ligases control Wnt signaling by targeting the Wnt receptor Frizzled to induce ubiquitination-mediated endo-lysosomal degradation, thus controlling the activation of the Wnt signaling pathway. We also discuss the regulatory mechanisms, interactors, and evolution of RNF43 and ZNRF3. This review article summarizes recent findings on RNF43 and ZNRF3 and their potential implications for the development of therapeutic strategies to target the Wnt signaling pathway in various diseases, including cancer.

• Proceedings of the Zoological Society Korea Conference
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• 1995.10b
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• pp.240.2-240
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• 1995

No Abstract, See Full Text

• Proceedings of the Korean Society of Potoscience Conference
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• 2005.06a
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• pp.49-49
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• 2005