• Title/Summary/Keyword: Signal Transduction

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Some Properties on the Signal Transduction in Virginiae Butanolide C Binding Protein (Virginiae Butanolide C 결합단백질의 신호 전달기구에 대한 연구)

  • 김현수
    • Korean Journal of Microbiology
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    • v.30 no.3
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    • pp.181-186
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    • 1992
  • Virginiae butanolide C (VB-C) binding protein binds to virginiamycin inducing factor and the protein may function as a possible pleiotropic signal transducer. To further understand signal transducing mechanism, some properties of VB-C binding protcin were investigated. VB-C binding activity was gradually increased during 60 hrs incubation: whereas the amount of produced VBs was not changed. However. VB-C hinding activity was decreased by 30-5096 in the presence of genome DNA. The binding protein could he phosphorylated by [$\gamma-^{32}\textrm{P}$] ATP. These results suggest that the DNA binding and phosphorylation may be involved in signal transducing mechanism.

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Toxic Effects of Alumina Nanoparticles in Rat Cerebrums and Kidneys (산화알루미늄 나노물질이 랫드의 대뇌와 신장에 미치는 영향)

  • Jo, Eunhye;Seo, Gyun-Baek;Kim, Hyunmi;Choi, Kyunghee;Kwon, Jung-Taek;Kim, Philje;Eom, Igchun
    • Journal of Environmental Health Sciences
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    • v.42 no.1
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    • pp.27-33
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    • 2016
  • Objectives: Alumina nanoparticles ($Al_2O_3$, Al-NPs) are used for various purposes, including as coating agents and paint additives. Their potential toxicity has raised concern for human health. This study focuses on exploring the toxic effects on the brain and kidneys caused by Al-NPs exposure in rats. Methods: The animals were orally administered Al-NPs at 10, 50 and 100 mg/kg body weight for 28 days following OECD TG 407. To determine the targeted toxicity of Al-NPs, histopathological examination and gene expression analysis were conducted on the rats. Results: The Al-NPs treatment induced kidney tubular dilatation. In the rat cerebrums, the expression levels of 126 genes experienced two-fold or greater increases in response to Al-NPs, including other genes encoding proteins involved in cell differentiation, transcription and signal transduction. In the rat kidneys, the expression levels of 152 genes also showed two-fold or greater increases in response to Al-NPs, including other genes encoding proteins involved in apoptosis, transcription and signal transduction. Conclusion: These results suggest that exposure to Al-NPs influences cellular signal pathways of kidney and cerebrum, and it can be a toxic indicators of nanometrials.

Up-Regulation of Interleukin-4 Receptor Expression by Interleukin-4 and CD40 Ligation via Tyrosine Kinase-Dependent Pathway

  • Kim, Hyun-Il;So, Eui-Young;Yoon, Suk-Ran;Han, Mi-Young;Lee, Choong-Eun
    • BMB Reports
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    • v.31 no.1
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    • pp.83-88
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    • 1998
  • Recently a B cell surface molecule, CD40, has emerged as a receptor mediating a co-stimulatory signal for B cell proliferation and differentiation. To investigate the mechanism of synergy between interleukin-4 (IL-4) and CD40 ligation in B cell activation, we have examined the effect of CE40 cross-linking on the IL-4 receptor expression in human B cells using anti-CE40 antibody. We observed that IL-4 and anti-CD40 both induce IL-4 receptor gene expression with a rapid kinetics resulting in a noticeable accumulation of IL-4 receptor mRNA within 4 h. While IL-4 caused a dose-dependent induction of surface IL-4 receptor expression, the inclusion of anti-CD40 in the IL-4-treated culture, further up-regulated the IL-4-induced IL-4 receptor expression as analyzed by flow cytometry. Pretreatment of B cells with inhibitors of protein tyrosine kinase (PTK) resulted in a significant inhibition of both the IL-4- and anti-CD40-induced IL-4 receptor mRNA levels, while protein kinase C (PKC) inhibitors had no effects. These results suggest that IL-4 and CD40 ligation generate B cell signals, which via PTK-dependent pathways, lead to the synergistic induction of IL-4 receptor gene expression. The rapid induction of IL-4 receptor gene expression through the tyrosine kinase-mediated signal transduction by B cell activating stimuli, would provide cells capacity for an efficient response to IL-4 in the early phase of IL-4 action, and may in part constitute the molecular basis of the reported anti-CD40 co-stimulatory effect on the IL-4-induced response.

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The Suppressive Effect of Th2 Cytokines Expression and the Signal Transduction Mechanism in MC/9 Mast Cells by Forsythiae Fructus Extracts (비만세포에서 연교(連翹) 추출물의 Th2 사이토카인 발현 및 신호전달 기전 억제 효과)

  • Lee, Jin Hwa;Han, Jae Kyung;Kim, Yun Hee
    • The Journal of Pediatrics of Korean Medicine
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    • v.28 no.3
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    • pp.31-46
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    • 2014
  • Objectives Forsythiae Fructus treatment has been used for inflammatory and allergic diseases in Korean Medicine. Nevertheless, the mechanism of action and the cellular targets are not understood well. The pathogenesis of allergic diseases are associated with Th2 cytokines such as IL-13, MIP-$1{\alpha}$, IL-13, IL-5, GM-CSF, IL-4, TNF-${\alpha}$ and IL-6, which are secreted by the mast cells. This study was conducted to investigate the effects of Forsythiae Fructus extracts (FF) on Th2 cytokines expression and signal transduction in MC/9 mast cells. Methods In the study, MC/9 mast cells were stimulated with DNP-IgE for 24 hours and then treated separately with CsA $10{\mu}g/m{\ell}$ and varying doses of FF for one hour. MC/9 mast cells stimulated with DNP-IgE was the control group, a treatment with CsA was the positive control group and a treatment with varying doses FF was the experimental groups. The mRNA levels of IL-13, IL-5, GM-CSF, IL-4, TNF-${\alpha}$, IL-6 were analyzed with Real-time PCR. The levels of IL-13, MIP-$1{\alpha}$ were measured using enzyme-linked immunosorbent assays(ELISA). NFAT, AP-1 and NF-${\kappa}B$ p65 were examined by Western blot analysis. Results 1. FF were observed to suppress the mRNA expression of IL-13, IL-5, GM-CSF, IL-4, TNF-${\alpha}$, IL-6 in comparison to DNP-IgE control group. 2. FF also has inhibited the IL-13, MIP-$1{\alpha}$ production significantly in comparison to DNP-IgE control group. 3. Western blot analysis of transduction factors involving Th2 cytokines expression has revealed a prominent decrease of the mast cell specific transduction factors including NFAT-1, NFAT-2, c-Jun, and NF-${\kappa}B$ p65 but c-Fos. Conclusions In conclusion, the anti-allergenic activities of FF may be strongly related to the regulation of transcription factors NFAT-1, NFAT-2, c-Jun, and NF-${\kappa}B$ p65 causing inhibition of Th2 cytokines in mast cells.

Regulatory Action of $\beta-adrenergic$ Agonist and 8-bromocyclic AMP on Calcium Currents in the Unfertilized Mouse Eggs

  • Haan, Jae-Hee;Cheong, Seung-Jin;Kim, Yang-Mi;Park, Choon-Ok;Hong, Seong-Geun
    • The Korean Journal of Physiology
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    • v.27 no.2
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    • pp.175-183
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    • 1993
  • There are many report suggesting that influx and intracellular calcium concentration $([Ca^{2+}]_i)$ are related to cell signalling in various cells. However, it has not been reported that calcium channel activation is affected by the substances involved in signal transduction pathways in the mouse eggs. In this study, the effects of isoprenaline (ISP) and cyclic AMP on calcium influx through calcium channels were investigated to show their relationship with the signal transduction process in unfertilized mouse eggs. Using whole cell voltage clamp techniques, calcium currents, elicited by the depolarizing pulses of 300 ms duration (from -50 mV to 50 mV in 10 mV increments) from a holding potential of -80 mV, were recorded. The current-voltage (I-V) relation of calcium currents was shown to be bell-shaped; the current began to activate at -50 mV and reached its maximum $(-1.33{\pm}0.16\;nA:\;mean{\pm}S.E.,\;n=7)$ at -10 mV, then decayed at around 50 mV. Calcium currents were fully activated within $7\;ms{\sim}20\;ms$ and completely inactivated 200 ms after onset of the step pulse. ISP within the concentration ranges of $10^{-8}\;M{\sim}10^{-4}\;M$ dose-dependently increased the amplitude calcium current. The permeable cyclic AMP analogue,8-bromocyclic AMP, also increased its maximal amplitude by 46ft at $10^{-5}\;M$, while protein kinase inhibitor (PKI), which is known to inhibit 0.02 phosphorylating units of cyclic AMP-dependent protein kinase (PKA) per microgram decreased calcium currents. Currents recorded in the presence of PKI were resistant to increase by the application of $10^{-5}\;M$. Also, PKI inhibited the calcium current increase elicited by ISP treatment. These results suggest that $\beta-adrenergic$ regulation of the calcium channel is mediated by the cAMP-dependent protein kinase. This signal transduction pathway might play a role in regulating $[Ca^{2+}]_i$, level due to the increase of calcium influx in mouse eggs.

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Differentially Up-expressed Genes Involved in Toluene Tolerance in Pseudomonas sp. BCNU106 (유기용매 내성 세균 Pseudomonas sp. BCNU106 균주에서 차별적으로 상향 발현되는 유전자군의 톨루엔 내성과의 연관성)

  • Joo, Woo Hong;Bae, Yun-Ui;Kim, Da Som;Kim, Dong Wan
    • Journal of Life Science
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    • v.30 no.1
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    • pp.88-95
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    • 2020
  • Using a random arbitrarily primed polymerase chain reaction, messenger RNA expression levels were assessed after exposure to 10% (v/v) toluene for 8 hr in solvent-tolerant Pseudomonas sp. BCNU 106. Among the 100 up-expressed products, 50 complementary DNA fragments were confirmed to express repeatedly; these were cloned and then sequenced. Blast analysis revealed that toluene stimulated an adaptive increase in the gene expression level in association with transcriptions such as LysR family of transcriptional regulators and RNA polymerase factor sigma-32. The expression of catalase and Mn2+/Fe2+ transporter genes functionally associated with inorganic ion transport and metabolism increased, and the increased expression of type IV pilus assembly PilZ and multi-sensor signal transduction histidine kinase genes, functionally categorized into signal transduction and mechanisms, was also demonstrated under toluene stress. The gene expression level of beta-hexosaminidase in association with carbohydrate transport and metabolism increased, and those of DNA polymerase III subunit epsilon, DNA-3-methyladenine glycosylase II, DEAD/DEAH box helicase domain-containing protein, and ABC transporter also increased after exposure to toluene in DNA replication, recombination, and repair, and even in defense mechanism. In particular, the RNAs corresponding to the ABC transporter, Mn2+/Fe2+ transporter, and the β-hexosaminidase gene were confirmed to be markedly induced in the presence of 10% toluene. Thus, defense mechanism, cellular ion homeostasis, and biofilm formation were shown as essential for toluene tolerance in Pseudomonas sp. BCNU 106.

Effect of ODAM and BMPRIB on Enamel Mineralization (ODAM과 BMPRIB가 법랑질의 석회화에 미치는 영향)

  • Park, Jong-Tae;Cho, Kwang-Hee;Bae, Hyun-Sook;Cho, Young-Sik;Kim, Heung-Joong
    • Journal of dental hygiene science
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    • v.11 no.1
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    • pp.55-61
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    • 2011
  • The purpose of this study was to investigate the biological function of ODAM and its signal transduction pathway in the steps of ameloblast differentiation and enamel mineralization. An ODAM recombinant protein was produced and stable ODAM transgenic cell lines were also established using ameloblast-lineage cells (ALCs). To verify the ODAM signal transduction pathway, BAMBI recombinant protein, an inhibitor of BMP2 and BMP receptor 1B (BMPR-1B), was treated and BMPR-1B siRNA was used to silence expression of BMPR-1B. Mineralization was augmented by the ALCs treated with the ODAM recombinant protein and the sense ODAM overexpressing cells. The ALP activity was also increased markedly in the sense ODAM overexpressing cells and the ALCs treated with ODAM recombinant protein. The inactivation of ODAM in the ALCs down-regulated the expression of BMPR-1B, whereas its expression was up-regulated markedly when ODAM was overexpressed. These results provide deeper insights into the process of ameloblast maturation and in enamel mineralization. It also suggested that ODAM augmented enamel mineralization.

Structural and Functional Analysis of Nitrogenase Fe Protein with MgADP bound and Amino Acid Substitutions (MgADP 결합 및 아미노산 치환 Nitrogenase Fe 단백질의 구조 및 기능 분석)

  • Jeong, Mi-Suk;Jang, Se-Bok
    • Journal of Life Science
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    • v.14 no.5
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    • pp.752-760
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    • 2004
  • The function of the [4Fe-4S] cluster containing iron (Fe-) protein in nitrogenase catalysis is to serve as the nucleotide-dependent electron donor to the MoFe protein which contains the sites for substrate binding and reduction. The ability of the Fe protein to function in this manner is dependent on its ability to adopt the appropriate conformation for productive interaction with the MoFe protein and on its ability to change redox potentials to provide the driving force required for electron transfer. The MgADP-bound (or off) conformational state of the nitrogenase Fe protein structure described reveals mechanisms for long-range communication from the nucleotide-binding sites to control affinity of association with the MoFe protein component. Two pathways, termed switches I and II, appear to be integral to this nucleotide signal transduction mechanism. In addition, the structure of the MgADP bound Fe protein provides the basis for the changes in the biophysical properties of the [4Fe-4S] observed when Fe protein binds nucleotides. The structures of the nitrogenase Fe protein with defined amino acid substitutions in the nucleotide dependent signal transduction pathways of the Switch I and Switch II have been determined by X-ray diffraction methods. These two pathways have been also implicated by site directed mutagenesis studies, structural analysis and analogies to other proteins that utilize similar nucleotide dependent signal transduction pathways. We have examined the validity of the assignment of these pathways in linking the signals generated by MgATP binding and hydrolysis to macromolecular complex formation and intermolecular electron transfer. The results provide a structural basis for the observed biophysical and biochemical properties of the Fe protein variants and interactions within the nitrogenase Fe protein-MoFe protein complex.

Signal Transduction of Eel Luteinizing Hormone Receptor (eelLHR) and Follicle Stimulating Hormone Receptor (eelFSHR) by Recombinant Equine Chorionic Gonadotropin (rec-eCG) and Native eCG

  • Byambaragchaa, Munkhzaya;Lee, So-Yun;Kim, Dae-Jung;Kang, Myung-Hwa;Min, Kwan-Sik
    • Development and Reproduction
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    • v.22 no.1
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    • pp.55-64
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    • 2018
  • Previous studies showed that recombinant equine chorionic gonadotropin ($rec-eCG{\beta}/{\alpha}$) exhibits both follicle-stimulating hormone (FSH) and luteinizing hormone (LH)-like activities in rat LHR- and FSHR-expressing cells. In this study, we analyzed signal transduction by eelFSHR and eelLHR upon stimulation with $rec-eCG{\beta}/{\alpha}$ and native eCG. The cyclic adenosine monophosphate (cAMP) stimulation in CHO-K1 cells expressing eelLHR was determined upon exposure to different doses (0-1,450 ng/mL) of $rec-eCG{\beta}/{\alpha}$ and native eCG. The $EC_{50$ values of $rec-eCG{\beta}/{\alpha}$ and native eCG were 172.4 and 786.6 ng/mL, respectively. The activity of $rec-eCG{\beta}/{\alpha}$ was higher than that of native eCG. However, signal transduction in the CHO PathHunter Parental cells expressing eelFSHR was not enhanced by stimulation with both agonist $rec-eCG{\beta}/{\alpha}$ and native eCG. We concluded that $rec-eCG{\beta}/{\alpha}$ and native eCG were completely active in cells expressing eelLHR, similar to the activity in the mammalian cells expressing LHRs. However, $rec-eCG{\beta}/{\alpha}$ and native eCG did not invoke any signaling response in the cells expressing eelFSHR. These results suggest that eCG has a potent activity in cells expressing eelLHR. Thus, we also suggest that $rec-eCG{\beta}/{\alpha}$ can induce eel maturation by administering gonadotropic reagents (LH), such as salmon pituitary extract.

The spy-gfp Operon Fusion in Salmonella Enteritidis and Salmonella Gallinarum Senses the Envelope Stress (Salmonella Enteritidis와 Salmonella Gallinarum의 세균막 스트레스를 인식하는 spy-gfp 오페론 융합)

  • Kang, Bo Gyeong;Bang, Iel Soo
    • Journal of Dairy Science and Biotechnology
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    • v.36 no.4
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    • pp.208-219
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    • 2018
  • Emergence of drug resistant strains of Salmonella enterica threatens milk processing and related dairy industries, thereby increasing the need for development of new anti-bacterials. Developments of antibacterial drugs are largely aimed to target the bacterial envelope, but screening their efficacy on bacterial envelope is laborious. This study presents a potential biosensor for envelope-specific stress in which a gfp reporter gene fused to spy gene encoding a periplasmic chaperone protein Spy (spheroplast protein y) that can sense envelope stress signals transduced by two major two-component signal transduction systems BaeSR and CpxAR in Salmonella enterica serovars Enteritidis and S. Gallinarum. Using spy-gfp operon fusions in S. Enterititis and S. Gallinarum, we found that spy transcription in both serovars was greatly induced when Salmonella cells were forming the spheroplast and were treated with ethanol or a membrane-disrupting antibiotic polymyxin B. These envelope stress-specific inductions of spy transcription were abrogated in mutant Salmonella lacking either BaeR or CpxR. Results illustrate that induction of Spy expression can be efficiently triggered by two-component signal transduction systems sensing envelope stress conditions, and thereby suggest that monitoring the spy transcription by spy-gfp operon fusions would be helpful to determine if developing antimicrobials can damage envelopes of S. Enteritidis and S. Gallinarum.