• Title/Summary/Keyword: induced signal

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Epidermal Growth Factor Receptor-Related DNA Repair and Radiation-Resistance Regulatory Mechanisms: A Mini-Review

  • Bai, Jing;Guo, Xiao-Guang;Bai, Xiao-Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.10
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    • pp.4879-4881
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    • 2012
  • Epidermal growth factor receptor (EGFR) overexpression is associated with resistance to chemotherapy and radiotherapy. The EGFR modulates DNA repair after radiation-induced damage through an association with the catalytic subunit of DNA protein kinase. DNA double-strand breaks (DSBs) are the most lethal type of DNA damage induced by ionizing radiation, and non-homologous end joining is the predominant pathway for repair of radiation-induced DSBs. Some cell signaling pathways that respond to normal growth factors are abnormally activated in human cancer. These pathways also invoke the cell survival mechanisms that lead to resistance to radiation. The molecular connection between the EGFR and its control over DNA repair capacity appears to be mediated by one or more signaling pathways downstream of this receptor. The purpose of this mini-review was not only to highlight the relation of the EGFR signal as a regulatory mechanism to DNA repair and radiation resistance, but also to provide clues to improving existing radiation resistance through novel therapies based on the above-mentioned mechanism.

Staurosporine Enhances Parathyroid Hormone-Induced Calcium Signal in UMR-106 Osteoblastic Cells

  • Lee, Suk-Kyeong;Paula H. Stern
    • Archives of Pharmacal Research
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    • v.22 no.2
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    • pp.119-123
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    • 1999
  • Parathyroid hormone (PTH) treatment of bone and kidney-derived cells not only activates adenyly cyclase buy also increases intracellular free calcium, and translocates protein kinase C (PKC) from cytosol to plasma membranes. We have found that acute phorbol ester pretreatment significantly decreases PTH-induced calcium transients and the effect of phorbol ester was antagonized by staurosporine (ST). Although the major effect of ST in that study was the reversal of the action of phorbol ester, it appeared that ST may also have promoted the effect of PTH directly. To further investigate the observation, we examined the effect of ST on the intracellular calcium transients induced by PTH and $\alpha$-thrombin ($\alpha$-TH). For calcium transient experiments, UMR-106 cells were loaded with 2 mM fluo-acetoxymethylester for 30 min at room temperature. The cells were then washed and suspended in buffer containing 1 mM calcium. Fluorescence was detected at 530 nm, with excitation at 505 nm. ST alone did not cause calcium transients, but enhanced the transients elicited by PTH response. added 5 min before the hormone. Another protein kinase inhibitor H-7 likewise enhanced the calcium responses elicited by PTH, while genistein did not affect PTH response. Calcium transients elicited by $\alpha$-TH were also enhanced by ST. The results suggest that there might be tonically activated endogenous protein kinase(s) which inhibit calcium signaling of some calcemic agents.

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Baicalin suppresses lipopolysaccharide-induced matrix metalloproteinase expression: action via the mitogen-activated protein kinase and nuclear factor κB-related protein signaling pathway

  • Ko, Seon-Yle
    • International Journal of Oral Biology
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    • v.46 no.1
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    • pp.51-59
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    • 2021
  • Periodontal disease is an inflammatory disease that affects the destruction of the bone supporting the tooth and connective tissues surrounding it. Periodontal ligament fibroblasts (PDLFs) induce overexpression of matrix metalloproteinase (MMP) involved in periodontal disease's inflammatory destruction. Osteoclasts take part in physiological bone remodeling, but they are also involved in bone destruction in many kinds of bone diseases, including osteoporosis and periodontal disease. This study examined the effect of baicalin on proteolytic enzymes' production and secretion of inflammatory cytokines in PDLFs and RAW 264.7 cells under the lipopolysaccharide (LPS)-induced inflammatory conditions. Baicalin inhibited the expression of the protein, MMP-1 and MMP-2, without affecting PDLFs' cell viability, suggesting its possibility because of the inhibition of phosphorylation activation of mitogen-activated protein kinase's p38, and the signal transduction process of nuclear factor κB (NFκB)-related protein. Also, baicalin reduced the expression of MMP-8 and MMP-9 in RAW 264.7 cells. This reduction is thought to be due to the inhibition of the signal transduction process of NFκB-related proteins affected by inhibiting p65RelA phosphorylation. Also, baicalin inhibited the secretion of nitric oxide and interleukin-6 induced by LPS in RAW 264.7 cells. These results suggest that baicalin inhibits connective tissue destruction in periodontal disease. The inhibition of periodontal tissue destruction may be a therapeutic strategy for treating inflammatory periodontal-diseased patients.

Fingernail electron paramagnetic resonance dosimetry protocol for localized hand exposure accident

  • Jae Seok Kim;Byeong Ryong Park;Minsu Cho;Won Il Jang;Yong Kyun Kim
    • Nuclear Engineering and Technology
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    • v.55 no.1
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    • pp.270-277
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    • 2023
  • Exposure to ionizing radiation induces free radicals in human nails. These free radicals generate a radiation-induced signal (RIS) in electron paramagnetic resonance (EPR) spectroscopy. Compared with the RIS of tooth enamel samples, that in human nails is more affected by moisture and heat, but has the advantages of being sensitive to radiation and easy to collect. The fingernail as a biological sample is applicable in retrospective dosimetry in cases of localized hand exposure accidents. In this study, the dosimetric characteristics of fingernails were analyzed in fingernail clippings collected from Korean donors. The dose response, fading of radiation-induced and mechanically induced signals, treatment method for evaluation of background signal, minimum detectable dose, and minimum detectable mass were investigated to propose a fingernail-EPR dosimetry protocol. In addition, to validate the practicality of the protocol, blind and field experiments were performed in the laboratory and a non-destructive testing facility. The relative biases in the dose assessment result of the blind and field experiments were 8.43% and 21.68% on average between the reference and reconstructed doses. The results of this study suggest that fingernail-EPR dosimetry can be a useful method for the application of retrospective dosimetry in cases of radiological accidents.

The Negative Role of PDE4 on PTH-induced Signaling in Osteoblasts (조골세포내 PDE4에 의한 PTH 신호의 음성적 조절)

  • Park, Hyo-Jung;Noh, A-Long-Sae-Mi;Lee, Jung-Min;Yim, Mi-Jung
    • YAKHAK HOEJI
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    • v.54 no.5
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    • pp.410-415
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    • 2010
  • We explored the role of phosphodiesterase 4 (PDE4) on parathyroid (PTH)-induced signaling in osteoblasts. PTH was shown to increase the activity of PDE, mainly PDE4, in osteoblasts, which is partly attributable to elevated PDE4B and PDE4D mRNA expression. The use of PDE4 inhibitor strengthened the PTH-induced extracellular signal-regulated kinase (ERK) and p38 MAP kinase (MAPK) activation. Furthermore, the PDE4 inhibitor stimulated PTH-induced receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL) expression in osteoblasts, which in turn increased osteoclast formation. Taken together, these data suggest the negative role of PDE4 on PTH-induced signaling in osteoblasts.

Ceramide Induces Cell Death through an ERK-dependent Mitochondrial Apoptotic Pathway in Renal Epithelial Cells

  • Jung, Soon-Hee
    • Korean Journal of Clinical Laboratory Science
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    • v.42 no.1
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    • pp.46-54
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    • 2010
  • Ceramide induces cell death in a variety of cell types however, the underlying molecular mechanisms related to renal epithelial cells remain unclear. The present study was undertaken to determine the role of extracellular signal-regulated protein kinase (ERK) in ceramide-induced cell death in renal epithelial cells. An established renal proximal tubular cell line of opossum kidney (OK) cells was used for this research. Ceramide induced apoptotic cell death in these cells. Western blot analysis showed that ceramide induced activation of ERK. The ERK activation and cell death induced by ceramide were prevented by the ERK inhibitor PD98059. Ceramide caused cytochrome C release from mitochondria into the cytosol as well as activation of caspase-3. Both effects were prevented by PD98059. The ceramide-induced cell death was also prevented by a caspase inhibitor. These results suggest that ceramide induces cell death through an ERK-dependent mitochondrial apoptotic pathway in OK cells.

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Modulation of Cardiac ATP-Sensitive $K^+$ Channels Via Signal Transduction Mechanisms During Ischemic Preconditioning

  • Han, Jin;Kim, Nari;Seog, Dae-Hyun;Kim, Euiyong
    • Journal of Life Science
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    • v.12 no.1
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    • pp.33-42
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    • 2002
  • In several species, a short period of ischemic preconditioning protects the heart by reducing the size of infarcts resulting from subsequent prolonged bouts of ischemia. The mechanism by which activation of ATP-sensitive $K^+$($K_ATP$) channels could provide the memory associated with ischemic preconditioning is still under debate. Several signal transduction pathways have been implicated in the mechanisms of protection induced by ischemic preconditioning. The exact receptor-coupled pathways involved in preconditioning remain to be identified. Likely extracellular agonists are those whose circulating levels increase under conditions that activate $K_ATP$ channels; these conditions include ischemia and ischemic preconditioning. Potential physiological agonists include the following: (1) nitric oxide; (2) catecholamine; (3) adenosine; (4) acetylcholine; (5) bradykinin and (6) prostacycline. The purpose of this review was to understand the mechanism by which biological signal transduction mechanism acts as a link in one or more known receptor-mediated pathways to increase $K_ATP$ channel activity during ischemic preconditioning.

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DC Current sensor using the saturable magnetic cores (자성체포화를 이용한 DC전류센서)

  • Park, Y.T.
    • Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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    • 2002.07b
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    • pp.699-702
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    • 2002
  • A DC current sensor is disclosed in which two pairs of saturable cores are provided so as enclose a conductor carrying a direct current to be measured. On each of the saturable cores, a bias winding, a feedback winding and an output winding are wound. Circuit for detection of an asymmetry in the magnetization current, generated by a reference alternating voltage, in a signal-conditioner. The reference alternating voltage is fed to the respective series circuits such that no resultant induction current is induced in the modulating current. The voltages over the resistor form input signals for two peak value detectors, the strength of the output signal of which represents the degree of asymmetry of magnetization current. This paper describes the development a DC current sensor and its signal-conditioner.

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Flow Velocity Measurement for Laminar Diffusion Flames Utilizing LII Signal from Soot Particles (매연입자의 LII 신호를 이용한 충류확산화염 유동속도 측정)

  • Lee, Jung-Soo;Nam, Youn-Woo;Lee, Won-Nam
    • 한국연소학회:학술대회논문집
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    • 2006.04a
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    • pp.157-163
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    • 2006
  • A new technique utilizing LII signal for the measurement of flow velocities of laminar diffusion flames has been investigated. Soot particles in ethylene diffusion flames are heated by a modulated Ar-ion laser beam. LII signals and their phase angles are measured using a lock-in amplifier at the different flame heights and the axial flow velocity are obtained from the measured phase angle delay. The measured velocities are similar to those from LDV measurements under the same operating conditions. The effects of laser power, LII signal wavelength, and modulation frequency are not sensitive to the velocity measurement. However, the choice of an optical chopper blade type could affect the measurement result. The use of a 6/5 chopper blade showed the better result that is possibly due to the square shape of modulated laser beam. This study successfully demonstrated that axial flow velocities of laminar diffusion flames can be measured by a new technique utilizing LII signal, which does not need particle seeding unlikely to LDV or PIV techniques.

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Changes in the Optogalvanic Signal Amplitude in a Hollow Cathode Discharge

  • Lee, Jun-Hoi;Koo, Kyung-Wan;Lee, Ki-Sik
    • Transactions on Electrical and Electronic Materials
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    • v.10 no.6
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    • pp.212-216
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    • 2009
  • The spatial distribution of the optogalvanic (OG) signal in argon at the 801.489 nm ($1s_5-2p_8$ transition at the metastable level in Paschen notation) was investigated in the radial direction of a hollow cathode discharge tube. The results of this experiment showed that the OG signal amplitude decreases in accordance with the following two conditions; first, the level of discharge current and second, the distance from the cathode dark space. These results can be quantified by analyzing the electron density profile along the discharge regions, which can directly influence the collisional ionization induced by electron impact.