• Title/Summary/Keyword: signal molecule

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Suppression of EGFR/STAT3 activity by lupeol contributes to the induction of the apoptosis of human non-small cell lung cancer cells

  • TAE‑RIN MIN;HYUN‑JI PARK;KI‑TAE HA;GYOO‑YONG CHI;YUNG‑HYUN CHOI;SHIN‑HYUNG PARK
    • International Journal of Oncology
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    • v.55 no.1
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    • pp.320-330
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    • 2019
  • The aim of this study was to investigate the underlying mechanisms responsible for the anticancer effects of lupeol on human non-small cell lung cancer (NSCLC). MTT assay and Trypan blue exclusion assay were used to evaluate the cell viability. DAPI staining and flow cytometric analysis were used to detect apoptosis. Molecular docking and western blot analysis were performed to determine the target of lupeol. We found that lupeol suppressed the proliferation and colony formation of NSCLC cells in a dose-dependent manner. In addition, lupeol increased chromatin condensation, poly(ADP-ribose) polymerase (PARP) cleavage, sub-G1 cell populations, and the proportion of Annexin V-positive cells, indicating that lupeol triggered the apoptosis of NSCLC cells. Notably, lupeol inhibited the phosphorylation of epithelial growth factor receptor (EGFR). A docking experiment revealed that lupeol directly bound to the tyrosine kinase domain of EGFR. We observed that the signal transducer and activator of transcription 3 (STAT3), a downstream molecule of EGFR, was also dephosphorylated by lupeol. Lupeol suppressed the nuclear translocation and transcriptional activity of STAT3 and downregulated the expression of STAT3 target genes. The constitutive activation of STAT3 by STAT3 Y705D overexpression suppressed lupeol-induced apoptosis, demonstrating that the inhibition of STAT3 activity contributed to the induction of apoptosis. The anticancer effects of lupeol were consistently observed in EGFR tyrosine kinase inhibitor (TKI)-resistant H1975 cells (EGFR L858R/T790M). Taken together, the findings of this study suggest that lupeol may be used, not only for EGFR TKI-naïve NSCLC, but also for advanced NSCLC with acquired resistance to EGFR TKIs.

Immunomodulating Activity of Fungal $\beta$-Glucan through Dectin-1 and Toll-like Receptor on Murine Macrophage

  • Kim, Ha-Won
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2006.11a
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    • pp.103-115
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    • 2006
  • $\beta$-Glucan is a glucose polymer that has linkage of $\beta$-(1,3), -(1,4) and -(1,6). As exclusively found in fungal and bacterial cell wall, not in animal, $\beta$-glucans are recognized by innate immune system. Dendritic cells (DC) or macrophages possesses pattern recognition molecule (PRM) for binding $\beta$-glucan as pathogen-associated molecular pattern (PAMP). Recently $\beta$-glucan receptor was cloned from DC and named as dectin-l which belongs to type II C-type lectin family. Human dectin-1 is consisted of 7 exons and 6 introns. The polypeptide of dectin-1 has 247 amino acids and has cytoplasmic, transmembrane, stalk and carbohydrate recognition domains. Dectin-1 could recognize variety of beta-1,3 and/or beta-1,6 glucan linkages, but not alpha-glucans. In our macrophage cell line culture system, dectin-1 mRNA was detected in RA W264.7 cells by reverse transcription-polymerase chain reaction (RT-PCR). Dectin-1 was also detected in the murine organs of spleen, thymus, lung and intestines. Treatment of RA W264.7 cells with $\beta$-glucans of Ganoderma lucidum (GLG) resulted in increased expression of IL-6 and TNF-$\alpha$ in the presence of LPS. However, GLG alone did not increase IL-6 nor TNF-$\alpha$. These results suggest that receptor dectin-1 cooperate with CD14 to activate signal transduction that is very critical in immunoresponse.

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A Role of Mitogen Activated Protein Kinases and Inflammatory Responses in Gender Differences in Kidney Ischemia Injury

  • Park, Kwon-Moo;Han, Ho-Jae
    • The Korean Journal of Physiology and Pharmacology
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    • v.6 no.3
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    • pp.155-160
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    • 2002
  • It is not known whether gender differences play a role in susceptibility to ischemic acute renal failure. Thus, we examined if there were any differences in susceptibility between male and female mice to kidney ischemic injury, and if so, whether it is due to differences in mitogen activated protein kinases (MAPKs) or inflammatory responses to ischemia. Female mice were protected against kidney ischemia when compared with males. Thirty minutes of bilateral ischemia resulted in marked functional and morphological damages in males, but not in females. The ischemia-induced phosphorylation of c-jun N-terminal stress-activated protein kinases (JNKs) was higher in males than in females. Phosphorylation of extracellular signal-regulated kinases (ERKs) was lower in males than in females. Post- ischemia medullary infiltration of RAW 264.7 cell, a monocyte-macrophage cell, and intercellular adhesion molecule-1 (ICAM-1) were greater in males than in females. In conclusion, males were much more susceptible to ischemia than females. The enhanced propensity to ischemic injury in males was correlated with greater activation of JNKs, greater expression of ICAM-1, and greater trapping of leukocytes in the medulla.

S-Adenosyl-L-Methionine Analogues to Enhance the Production of Actinorhodin

  • Chong You-Hoon;Young Jung-Mo;Kim Jin-Young;Lee Yu-Kyung;Park Kwang-Su;Cho Jun-Ho;Kwon Hyung-Jin;Suh Joo-WOn;Lim Yoong-Ho
    • Journal of Microbiology and Biotechnology
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    • v.16 no.7
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    • pp.1154-1157
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    • 2006
  • It is known that overexpression of S-adenosyl-L-methionine (SAM) synthetase or exogenous addition of SAM enhances the production of actinorhodin, one of pigmented antibiotics found from Streptomyces coelicolor. In order to discover a novel compound as a signal molecule to produce actinorhodin instead of SAM, several compounds were synthesized based on the relationships between structures of the SAM analogues and their actinorhodin productivities. Of these, a few compounds showed better productivities of actinorhodin than SAM.

Functional Analysis of Olfactory Receptors Expressed in a HEK-293 Cell System by Using Cameleons

  • Ko, Hwi-Jin;Park, Tai-Hyun
    • Journal of Microbiology and Biotechnology
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    • v.17 no.6
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    • pp.928-933
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    • 2007
  • Cameleon is a genetically engineered $Ca^{2+}$ sensing molecule consisting of two variants of the green fluorescent protein (GFP), calmodulin and calmodulin-binding protein, M13. HEK-293 cells stably expressing three types of cameleons, yellow cameleon-2, cameleon-3er, and cameleon-2nu, were constructed, and the expression and localization of these cameleons were confirmed by fluorescent imaging. Among the cameleons, the yellow cameleon-2 was selected for analyzing the change in $Ca^{2+}$ induced by the olfactory receptor-mediated signal transduction, because it is localized in the cytosol and binds to cytosolic $Ca^{2+}$ ions. Cells stably expressing yellow cameleon-2 were transfected with each of the test olfactory receptor genes, odr-10 and 17, and the expression of the olfactory receptor genes were examined using immunocytochenmical methods and RT-PCR. Stimulating each olfactory receptor with its specific odorant caused an increase in the intracellular $Ca^{2+}$ level, which was measured using yellow cameleon-2. These results demonstrate that yellow cameleon-2 can be conveniently used to examine the function of the olfactory receptors expressed in heterologous cells.

Immunomodulating Activity of Fungal ${\beta}-Glucan$ through Dectin-1 and Toll-like Receptor on Murine Macrophage

  • Kim, Ha-Won
    • 한국약용작물학회:학술대회논문집
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    • 2006.11a
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    • pp.103-115
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    • 2006
  • [ ${\beta}-Glucan$ ] is a glucose polymer that has linkage of ${\beta}-(1,3)$, -(1,4) and -(1,6). As exclusively found in fungal and bacterial cell wall, not in animal, ${\beta}-glucans$ are recognized by innate immune system. Dendritic cells (DC) or macrophages possesses pattern recognition molecule (PRM) for binding ${\beta}-glucans$ as pathogen-associated molecular pattern (PAMP). Recently ${\beta}-glucans$ receptor was cloned from DC and named as dectin-l which belongs to type II C-type lectin family. Human dectin-l is consisted of 7 exons and 6 introns. The polypeptide of dectin-l has 247 amino acids and has cytoplasmic, transmembrane, stalk and carbohydrate recognition domains. Dectin-l could recognize variety of beta-l,3 and/or beta-l,6 glucan linkages, but not alpha-glucans. In our macrophage cell line culture system, dectin-l mRNA was detected in RA W264.7 cells by reverse transcription-polymerase chain reaction (RT-PCR). Dectin-l was also detected in the murine organs of spleen, thymus, lung and intestines. Treatment of RA W264.7 cells with ${\beta}-glucans$ of Ganoderma lucidum (GLG) resulted in increased expression of IL-6 and $TNF-{\alpha}$ in the presence of LPS. However, GLG alone did not increase IL-6 nor $TNF-{\alpha}$ These results suggest that receptor dectin-l cooperate with CD14 to activate signal transduction that is very critical in immunoresponse.

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Proposal and Evaluation of Ultra High Speed Wireless Cell Backbone Networks (도시형 초고속 무선통신 셀백본망의 제안 및 평가)

  • 신천우
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.29 no.2B
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    • pp.151-157
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    • 2004
  • In this paper, we investigated ultra high speed wireless communication cell backbone net of city using of wireless communication transceiver for millimeter wave band. A new type of 60GHz wave band wireless transceiver using NRD waveguide. This 60㎓ transceiver has excellent signal's absorption characteristics of oxygen molecule than the other millimeter wave bands. We constructed to wireless networks interval within 500m to 3km on wireless backbone node using 60GHz transceivers, and did it so that city type wireless communication cell backbone networks of 155.52MbpsATM(OC-3) may be possible. Therefore, if use transceiver, it is possible that city type ultra high speed wireless communication cell backbone networks construction of 100Mbps, 155.52Mbps, 622Mbps, 1Gbps, and 1.2Gbps degrees.

The Protein Kinase Activity of Phytochrome Functions in Regulating Plant Light Signaling

  • Shin, Ah-Young;Han, Yun-Jeong;Song, Pill-Soon;Kim, Jeong-Il
    • Rapid Communication in Photoscience
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    • v.2 no.2
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    • pp.56-59
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    • 2013
  • Plant phytochromes, molecular light switches that regulate various aspects of plant growth and development, are known as autophosphorylating serine/threonine kinases. Although recent studies reveal that phytochrome autophosphorylation plays an important role in the regulation of phytochrome signaling through the control of phyA protein stability, the in vivo functional roles of phytochrome kinase activity in plant light signaling are largely unknown. Thus, it is necessary to investigate the detailed function of phytochrome as a protein kinase, which might include mapping of kinase domain on the phytochrome molecule, searching for substrates that could be phosphorylated by phyA, and in vivo functional analysis of the kinase activity with phytochrome mutants displaying reduced kinase activity. Our recent studies reveal that the kinase activity of phytochrome plays a positive role in plant light signaling. Therefore, we highlight the current knowledge about the functional roles of phytochrome kinase activity in the light signal transduction of plants, based on our recent results.

Analysis of Xe Plasma by LAS (레이저 흡수법을 이용한 제논 플라즈마 분석)

  • Yang, Jong-Kyung;Her, In-Sung;Lee, Jong-Chan;Choi, Yong-Sung;Park, Dae-Hee
    • Proceedings of the KIEE Conference
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    • 2005.11a
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    • pp.220-222
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    • 2005
  • We can classify two cases in a way to observe an atom of gas state or a molecule using the laser. First case is way to use dispersion phenomenon like Rayleigh scattering, Thomson scattering, Mie scattering, Raman Scattering. And Second case is a way to use change phenomenon like a LAS (Laser Absorption Spectroscopy), LIF (Laser Induced Fluorescent). In this paper, we have measured the meta-stable density and the distribution by using a LAS method in Xe discharge lamp. The laser absorption spectroscopy (LAS) is useful to investigate the behavior of such species. The xenon atoms in the $1S_4$ and $1S_5$ generate excited $Xe^*$(147nm) and $Xe_{2}^*$(173nm) dimers in Xe plasma. It is found that the intensity of VUV 147nm emission is proportional to that of the IR 828nm emission, and the VUV 173nm emission is roughly proportional to that of the IR 823nm emission. The laser is used CW laser that consist of AlGaAs semiconductor and energy level is used 823.16nm wavelength. We measured signal of monochrometer from the lamp center while will change a discharge electric current by 6mA in 3mA and calculated meta-stable state density of a xenon atom through a measured value.

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Various Sensor Applications Based on Conjugated Polymers

  • Lee, Chang-Lyoul
    • Proceedings of the Korean Vacuum Society Conference
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    • 2014.02a
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    • pp.103.1-103.1
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    • 2014
  • Due to their excellent optical and electrochemical properties, conjugated polymers have attracted much attention over the last two decades and employed to opto-electrical devices. In particular, conjugated polymers possess many attractive features that make them suitable for a variety of sensing task. For example, their delocalized electronic structures can be strongly modified by varying the surrounding environment, which significantly affected molecular energy level. In other word, conjugated polymers can detect and transduce the environmental information into a fluorescence signal. Conjugated polymers also display amplified quenching compared to small molecule counterparts. This amplified fluorescence quenching is attributed to the delocalization and migration of the excitons along the conjugated polymer backbones. Long backbones of conjugated polymer provide the transporting path for electron as a conduit, allowing that excitons migrate rapidly into quencher site along the backbone. This is often referred to as the molecular wire effect or antenna effect. Moreover, structures of conjugated polymers can be easily tailored to adjust solubility, absorption/emission properties, and regulation of electron/energy transfer. Based on this versatility, conjugated polymers have been utilized to many novel sensory platforms as a promising material. In this tutorial, I will highlight a variety of fluorescence sensors base on conjugated polymer and explain their sensory mechanism together with selected examples from reference literatures.

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