• Title/Summary/Keyword: Gene Regulation

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Text-mining Techniques for Metabolic Pathway Reconstruction (대사경로 재구축을 위한 텍스트 마이닝 기법)

  • Kwon, Hyuk-Ryul;Na, Jong-Hwa;Yoo, Jae-Soo;Cho, Wan-Sup
    • Journal of Korea Society of Industrial Information Systems
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    • v.12 no.4
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    • pp.138-147
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    • 2007
  • Metabolic pathway is a series of chemical reactions occuning within a cell and can be used for drug development and understanding of life phenomenon. Many biologists are trying to extract metabolic pathway information from huge literatures for their metabolic-circuit regulation study. We propose a text-mining technique based on the keyword and pattern. Proposed technique utilizes a web robot to collect huge papers and stores them into a local database. We use gene ontology to increase compound recognition rate and NCBI Tokenizer library to recognize useful information without compound destruction. Furthermore, we obtain useful sentence patterns representing metabolic pathway from papers and KEGG database. We have extracted 66 patterns in 20,000 documents for Glycosphingolipid species from KEGG, a representative metabolic database. We verify our system for nineteen compounds in Glycosphingolipid species. The result shows that the recall is 95.1%, the precision 96.3%, and the processing time 15 seconds. Proposed text mining system is expected to be used for metabolic pathway reconstruction.

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Protective Effect of Ginsenoside Rb1 on Hydrogen Peroxide-induced Oxidative Stress in Rat Articular Chondrocytes

  • Kim, Sok-Ho;Na, Ji-Young;Song, Ki-Bbeum;Choi, Dea-Seung;Kim, Jong-Hoon;Kwon, Young-Bae;Kwon, Jung-Kee
    • Journal of Ginseng Research
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    • v.36 no.2
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    • pp.161-168
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    • 2012
  • The abnormal maturation and ossification of articular chondrocytes play a central role in the pathogenesis of osteoarthritis (OA). Inhibiting the enzymatic degradation of the extracellular matrix and maintaining the cellular phenotype are two of the major goals of interest in managing OA. Ginseng is frequently taken orally, as a crude substance, as a traditional medicine in Asian countries. Ginsenoside $Rb_1$, a major component of ginseng that contains an aglycone with a dammarane skeleton, has been reported to exhibit various biological activities, including anti-inflammatory and anti-tumor effects. However, a chondroprotective effect of ginsenoside $Rb_1$ related to OA has not yet been reported. The purpose of this study was to demonstrate the chondroprotective effect of ginsenoside $Rb_1$ on the regulation of pro-inflammatory factors and chondrogenic genes. Cultured rat articular chondrocytes were treated with 100 ${\mu}M$ ginsenoside $Rb_1$ and/or 500 ${\mu}M$ hydrogen peroxide ($H_2O_2$) and assessed for viability, reactive oxygen species production, nitric oxide (NO) release, and chondrogenic gene expression. Ginsenoside $Rb_1$ treatment resulted in reductions in the levels of pro-inflammatory cytokine and NO in $H_2O_2$-treated chondrocytes. The expression levels of chondrogenic genes, such as type II collagen and SOX9, were increased in the presence of ginsenoside $Rb_1$, whereas the expression levels of inflammatory genes related to chondrocytes, such as MMP1 and MMP13, were reduced by approximately 50%. These results suggest that ginsenoside $Rb_1$ has potential for use as a therapeutic agent in OA patients.

Molecular Dynamics Simulation Study for Ionic Strength Dependence of RNA-host factor Interaction in Staphylococcus aureus Hfq

  • Lazar, Prettina;Lee, Yun-O;Kim, Song-Mi;Chandrasekaran, Meganathan;Lee, Keun-Woo
    • Bulletin of the Korean Chemical Society
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    • v.31 no.6
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    • pp.1519-1526
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    • 2010
  • The behavior of peptide or protein solutes in saline aqueous solution is a fundamental topic in physical chemistry. Addition of ions can strongly alter the thermodynamic and physical properties of peptide molecules in solution. In order to study the effects of added ionic salts on protein conformation and dynamics, we have used the molecular dynamics (MD) simulations to investigate the behavior of Staphylococcus aureus Hfq protein under two different ionic concentrations: 0.1 M NaCl and 1.0 M NaCl in presence and absence of RNA (a hepta-oligoribonucleotide AU5G). Hfq, a global regulator of gene expression is highly conserved and abundant RNA-binding protein. It is already reported that in vivo the increase of ionic strength results in a drastic reduction of Hfq affinity for $Q{\beta}$ RNA and reduces the tendency of aggregation of Escherichia coli host factor hexamers. Our results revealed the crucial role of 0.1 M NaCl Hfq system on the bases with strong hydrogen bonding interactions and by stabilizing the aromatic stacking of Tyr42 residue of the adjacent subunits/monomers with the adenine and uridine nucleobases. An increase in RNA pore diameter and weakened compactness of the Hfq-RNA complex was clearly observed in 1.0 M NaCl Hfq system with bound RNA. Aggregation of monomers in Hfq and the interaction of Hfq with RNA are greatly affected due to the presence of high ionic strength. Higher the ionic concentration, weaker is the aggregation and interaction. Our results were compatible with the experimental data and this is the first theoretical report for the experimental study done in 1980 by Uhlenbeck group for the present system.

Regulation of LIF Gene Expression by Interleukin-1 in the Mouse Peri-implantation Embryos and Uterine Endometrial Cells (생쥐의 착상시기 배아와 자궁내막세포에서 IL-1에 의한 LIF 유전자 발현 조절)

  • Lee, Jung-Bok;Kim, Joung-Woul;Oh, Eun-Jeong;Yang, Hye-Young;Ryu, Hyoung-Eun;Lee, Ji-Youn;Gye, Myung-Chan;Yoon, Hyun-Soo;Kim, Moon-Kyoo
    • Clinical and Experimental Reproductive Medicine
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    • v.27 no.2
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    • pp.183-190
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    • 2000
  • 연구목적: 포유류의 착상은 배아가 모체의 자궁벽에 매몰되는 현상으로 부착과 침투 과정을 거쳐 진행되며, 이 과정은 스테로이드 호르몬, 성장인자, 세포점착분자, 그리고 cytokine 등의 상호작용으로 이루어진다. 이 시기에 Interleukin-1 (IL-1)과 leukemia inhibitory factor (LIF) 등이 발현되는 것으로 알려져 있다. 본 실험에서는 이들의 발현이 착상과정에 어떠한 역할을 하는지 그 상관관계를 알아보고자 하였다. 재료 및 방법: 착상 전후의 배아와 자궁내막세포에서 LIF 유전자의 발현양상과 $IL-1{\beta}$와 IL-1 receptor antagonist (IL-1ra)를 처리한 LIF 유전자의 발현양상을 역전사중합효소연쇄반응 (RT-PCR)을 통해 비교하였다. 결과: 배아에서의 LIF 유전자 발현은 in vivo와 in vitro 모두에서 상실기와 포배기에 발현되었고, 자궁내막에서는 임신 1일과 4일째에 발현되었는데, 상실기보다는 포배기에, 그리고 임신 1일보다는 착상시기인 4일째의 자궁내막세포에서 발현양이 많은 것으로 나타났다. 자궁내막세포를 배양한 경우 LIF 유전자는 in vivo에서의 발현양상과 동일하게 임신 1일과 4일에 발현되었으며, 배양액에 $IL-1{\beta}$(500pgml)를 처리하였을 경우 LIF 유전자가 초기 임신 (1~5일) 중 발현되는 것으로 나타났다. 2-세포기 배아의 배양시에 $IL-1{\beta}$를 처리한 경우 8-세포기부터 LIF 유전자가 발현되었으며, 또한 IL-1ea(60 ng/ml)를 배양액에 첨가하였을 경우에는 임신1일째 자궁내막에서는 LIF 유전자가 발현되지 않은 반면, 임신 4일째의 자궁내막세포와 상실기, 포배기 배아 모두에서 LIF 유전자 발현이 감소하는 경향을 보였다. 결론: 이러한 결과는 착상 전후 배아와 자궁내막세포에서 IL-1에 의해 LIF 유전자 발현이 조절되며, 그 결과 착상에 영향을 줄 수 있다는 것을 의미한다. 또한 배아와 자궁내막세포에서 IL-1이 LIF 유전자 발현에 영향을 주는 것으로 보아 착상을 위해 IL-1과 LIF의 상호작용이 중요한 요인이라는 것을 확인할 수 있었다.

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THE EFFECT OF PKC PATHWAY & MAPK PATHWAY ON RUNX2 TRANSCRIPTIONAL ACTIVITY (Protein kinase C 및 MAPK pathway가 Runx2의 전사 활성에 미치는 영향)

  • Kim, Eun-Jung;Kim, Hyun-Jung;Ryoo, Hyun-Mo;Kim, Hyun-Jung;Kim, Young-Jin;Nam, Soon-Hyeun
    • Journal of the korean academy of Pediatric Dentistry
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    • v.29 no.3
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    • pp.337-344
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    • 2002
  • Runx2, a Runt-related osteoblast-specific transcription factor, is essential for osteoblast differentiation and function. Runx2 was identified as a key regulator of osteoblast-specific gene expression through its binding to the OSE2 element present in these genes. However, little is known about the signaling mechanism regulating Runx2 activity. This study examines the role of protein kinase C (PKC) pathway and mitogen-activated protein kinase (MAPK) pathway in regulating Runx2 and bone marker genes (osteopontin; OP, osteocalcin; OC). Luciferase assay and Northern blot analysis suggested that the stimulation of PKC by PMA increased transcription activity of Runx2 and bone marker genes (OP and OC) and also increased expression of Runx2. The stimulation of MAPK by okadaic acid increased transcription activity of Runx2 and bone marker genes (OP and OC). Pretreatment with PD98059 (Erk pathway inhibitor) and SB203580 (P38 pathway inhibitor) prior to PMA treatment decreased PMA stimulated Runx2 activity. Together these results indicate that both PKC and MAPKs are involved in the regulation of Runx2 activity and also the stimulation of Runx2 transcriptional activity by the PKC pathway is through activation of MAPK pathway.

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SB202190- and SB203580-Sensitive p38 Mitogen-Activated Protein Kinase Positively Regulates Heat Shock- and Amino Acid Analog-Induced Heat Shock Protein Expression

  • Kim, Sun-Hee;Han, Song-Iy;Oh, Su-Young;Seo, Myoung-Suk;Park, Hye-Gyeong;Kang, Ho-Sung
    • 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.

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Antimelanogenesis and skin-protective activities of Panax ginseng calyx ethanol extract

  • Lee, Jeong-Oog;Kim, Eunji;Kim, Ji Hye;Hong, Yo Han;Kim, Han Gyung;Jeong, Deok;Kim, Juewon;Kim, Su Hwan;Park, Chanwoong;Seo, Dae Bang;Son, Young-Jin;Han, Sang Yun;Cho, Jae Youl
    • Journal of Ginseng Research
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    • v.42 no.3
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    • pp.389-399
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    • 2018
  • Background: The antioxidant effects of Panax ginseng have been reported in several articles; however, little is known about the antimelanogenesis effect, skin-protective effect, and cellular mechanism of Panax ginseng, especially of P. ginseng calyx. To understand how an ethanol extract of P. ginseng berry calyx (Pg-C-EE) exerts skin-protective effects, we studied its activities in activated melanocytes and reactive oxygen species (ROS)-induced keratinocytes. Methods: To confirm the antimelanogenesis effect of Pg-C-EE, we analyzed melanin synthesis and secretion and messenger RNA and protein expression levels of related genes. Ultraviolet B (UVB) and hydrogen peroxide ($H_2O_2$) were used to induce cell damage by ROS generation. To examine whether this damage is inhibited by Pg-C-EE, we performed cell viability assays and gene expression and transcriptional activation analyses. Results: Pg-C-EE inhibited melanin synthesis and secretion by blocking activator protein 1 regulatory enzymes such as p38, extracellular signal-regulated kinases (ERKs), and cyclic adenosine mono-phosphate response element-binding protein. Pg-C-EE also suppressed ROS generation induced by $H_2O_2$ and UVB. Treatment with Pg-C-EE decreased the expression of matrix metalloproteinases, mitogen-activated protein kinases, and hyaluronidases and increased the cell survival rate. Conclusion: These results suggest that Pg-C-EE may have antimelanogenesis properties and skin-protective properties through regulation of activator protein 1 and cyclic adenosine monophosphate response element-binding protein signaling. Pg-C-EE may be used as a skin-improving agent, with moisture retention and whitening effects.

P53 Expression in Squamous Cell Carcinomas of Tongue and Tonsil (설과 편도 편평 상피세포암에서 P53의 표현양상에 관한 연구)

  • Choi, Geon;Kim, Man-Su;Choi, Jong-Ouck;Hwang, Soon-Jae;Yoo, Hong-Kyun
    • Proceedings of the KOR-BRONCHOESO Conference
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    • 1993.05a
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    • pp.83-83
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    • 1993
  • The nuclear phosphoprotein p53 is expressed in all normal cells and appears to function in cell cycle regulation. Abnormally high levels of the protein are found in many different types of cancer. In human cancer overexpression of p53 is associated with point mutations within highly conserved regions of p53 gene. These altered genes encode stable p53 proteins that can detected by standard immunocytochemical techniques unable to detect rapidly degraded wild-type protein. Using of a monoclonal antibody to p53 antigen, immunocytochemical analysis of 29 squamous cell carcinomas of tongue(n= 19) and tonsil(n= 10) was performed. Non-tumor nuclei showed all negative reactivity. Positive reactivity was found in 4/29(13.8%)of SCCs of tongue and tonsil. In sizes of primary tumor, the cases over 4cm showed more positive reactivity than the cases under 4cm(p < 0.05). There was no stastical correlation between the reactivity and histopathologic grades, the primary sites of tumor or the presence of cervical metastasis.

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Bioinformatics Analysis of Gene Expression Regulation by Transposable Elements in Dementia Patients (치매환자에서 transposable elements에 의한 유전자 발현조절의 생물정보 분석)

  • Kim, Dae-Soo;Huh, Jae-Won;Ha, Hong-Seok;Kim, Tae-Hong;Jo, Un-Jong;Kim, Heui-Soo
    • Journal of Life Science
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    • v.16 no.7 s.80
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    • pp.1188-1194
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    • 2006
  • Dementia is a progressive disease of increasing the dysfunction of intellectual and physical ability. In the aging society, many families are suffering from the caring the patients who are diagnosed with dementia. However, dementia is a complex disease affected by the genetic and environmental agents. In the present study, we investigated the transposable elements in relation to dementia. From the analysis of dementia EST (expressed sequence tag) sequences, we found dementia candidate genes, and analyzed expression profiles and repeat elements using bioinformatics tools. This analysis showed that 98 genes were affected in their mRNA sequences by transposable elements expression. Their expressions were affected by the integration of different transposable elements (SINE, LINE, LTR, DNA) during the primate evolution. We believe that our work will be of significant interest to genome scientists, and may help them gain insight into implication of transposable elements expression in dementia.

Myxococcus xanthus socD500 mutation causes Sporulation and Induction of two C-signal Specific Genes (Myxococcus xanthus socD500에 의한 포자 형성 및 CsgA신호에 특이적 유전자의 발현에 관한 연구)

  • 이병욱
    • Journal of Life Science
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    • v.13 no.2
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    • pp.184-190
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    • 2003
  • Myxococcus xanthus is a Gram negative, rod-shaped, soil bacterium that displays a social behaviors, and multicellular development upon nutrient deprivation. The csgA gene encoding a cell surface protein is essential for developmental behaviors including rippling, aggregation, fruiting body formation and sporulation. csgA mutants show normal vegetative growth, but lack all these developmental phenotypes. Expression of the CsgA (C-signal) specific genes are eliminated or dramatically reduced in csgA mutants. In order to identify components of C-signal transduction pathway, second site mutations were introduced into csgA mutants and were identified which can fully or partially restore development of csgA mutants (Rhie, H. G. et. al. 1989. J. Bacteriol. 171, 3268-3276). One of such csgA suppressor mutations, socD500 restores only sporulation to csgA mutants at 15$^{\circ}C$. The socD500 mutaion however eliminates the three basic developmental requirements, starvation, high cell density and a solid surface. Only sporulation, not accompanied with fruiting body formation is induced simply by shifting the temperature of vegetatively growing cells from $32^{\circ}C$ to $15^{\circ}C$. Spores induced by socD500 mutation is not as thick as that of wild-type fruiting body. In socD500 genetic background, two of ten C-signal dependent genes, $\Omega$DK4506 and $\Omega$DK4406 are more highly expressed in growing cells at $15^{\circ}C$. These results indicate that the socD500 mutation may be partly involved in the regulation of expression of two C-signal dependent genes and genes for sporulation in this transduction pathway.