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Insulin-Like Growth Factor-I Induces Androgen Receptor Activation in Differentiating C2C12 Skeletal Muscle Cells

  • Kim, Hye Jin;Lee, Won Jun
    • Molecules and Cells
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    • v.28 no.3
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    • pp.189-194
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    • 2009
  • The modulating effect of IGF-I on the regulation of AR gene expression and activation in skeletal muscle cells remains poorly understood. In this study, the effects of IGF-I treatment on AR induction and activation in the absence of AR ligands were examined. Differentiating C2C12 cells were treated with different concentrations (0-250 ng/ml) of IGF-I or for various periods of time (0-60 min) of 250 ng/ml IGF-I. Treatment of C2C12 cells with IGF-I resulted in a dose- and time-dependent increase in total AR and phosphorylated AR (Ser 213). IGF-I treatment also led to significantly increased AR mRNA expression when compared with the control. The levels of skeletal ${\alpha}-actin$ and myogenin mRNA, known target genes of AR, were also significantly upregulated after 5 or 10 min of treatment with IGF-I. Confocal images revealed that IGF-I stimulated nuclear localization of AR in the absence of ligands. In addition, an electrophoretic mobility shift assay indicated that IGF-I stimulated the AR DNA binding activity in a time-dependent manner. The present results suggest that IGF-I stimulates the expression and activation of AR by ligand-independent mechanism in differentiating C2C12 mouse skeletal muscle cells.

Design of Security RoadMap for C4I System (C4I 시스템 보안 로드맵 설계)

  • Lee, Gang-Taek;Lee, Dong-Hwi;Yang, Jae-Su;J. Kim, Kui-Nam;Park, Sang-Min
    • Convergence Security Journal
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    • v.6 no.4
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    • pp.113-120
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    • 2006
  • C4I system is the centerpiece of the military force. The system is an information based system which facilitates information grid, collection of data and dissemination of the information. The C4I system seeks to assure information dominance by linking warfighting elements in the battlespace to information network which enables sharing of battlespace information and awareness; thereby shifting concept of warfare from platform-centric paradigm to Network Centric Warfare. Although, it is evident that C4I system is a constant target from the adversaries, the issues of vulnerability via cyberspace from attack still remains. Therefore, the protection of C4I system is critical. The roadmap I have constructed in this paper will guide through the direction to protect the system during peace and war time. Moreover, it will propose vision, objectives and necessary supporting framework to secure the system from the threat. In order to fulfill these tasks, enhanced investments and plans from the Joint chief of Staff and Defense of Acquisition and Program Administration (DAPA) is critical; thereby enabling the establishment of rapid and efficient security system.

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Development of Reliability Evaluation System for I&C System Upgrade (원자력발전소 I&C계통 설비개선을 위한 평가시스템 개발)

  • Chung, Hak-Young;Kang, Hyeon-Tae;Sung, Chan-Ho
    • The Transactions of The Korean Institute of Electrical Engineers
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    • v.56 no.10
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    • pp.1852-1858
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    • 2007
  • To Increase availability and to enhance the safety, the modernization of Instrumentation & Control (I&C) systems is considered. The extended use of the digital technology lets nuclear power plants(NPPs) to replace their old analog systems with some proven digital systems. To adapt digital equipment to plants effectively and systematically, however, there must be an essential prerequisite, which is to evaluate current I&C equipment. This paper shows a practical methodology to evaluate the current status and reliability of I&C systems of NPPs using Reliability Evaluation System(RES) before performing upgrades or replacements for systems. The proposed method was applied to KORI Unit 2. The proposed method shows the current status of operating I&C systems effectively for upgrading I&C systems.

Insulin-like Growth Factor-I Modulates BDNF Expression by Inhibition of Histone Deacetylase in C2C12 Skeletal Muscle Cells (C2C12 골격근 세포에서 히스톤 탈 아세틸 효소의 억제가 인슐린 유사성장인자(IGF-I)에 의한 BDNF 발현 조절에 미치는 영향)

  • Kim, Hye Jin;Lee, Won Jun
    • Journal of Life Science
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    • v.27 no.8
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    • pp.879-887
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    • 2017
  • It is well established that brain-derived neurotrophic factor (BDNF) is expressed not only in the brain but also in skeletal muscle, and is required for normal neuromuscular system function. Histone deacetylases (HDACs) and insulin-like growth factor-I (IGF-I) are potent regulators of skeletal muscle myogenesis and muscle gene expression, but the mechanisms of HDAC and IGF-I in skeletal muscle-derived BDNF expression have not been examined. In this study, we examined the effect of IGF-I and suberoylanilide hydroxamic acid (SAHA), a pan-HDAC inhibitor, on BDNF induction. Proliferating or differentiating C2C12 skeletal muscle cells were treated with increasing concentrations (0-50 ng/ml) of IGF-I in the absence or presence of $5{\mu}M$ SAHA for various time periods (3-24 hr). Treatment of C2C12 cells with IGF-I resulted in a dose- and time-dependent decrease in BDNF mRNA expression. However, inhibition of HDAC led to a significant increase in the expression of BDNF mRNA levels. In addition, immunocytochemistry revealed high BDNF protein levels in undifferentiated C2C12 skeletal muscle cells, whether untreated, IGF-I-treated, or exposed to SAHA. These results represent the first evidence that IGF-I can suppress the mRNA and protein expression of BDNF; conversely, SAHA attenuates the effects of IGF-I. Consequently, SAHA upregulates BDNF expression in C2C12 skeletal muscle cells.

Updated Meta-analysis of the Association Between CYP2E1 RsaI/PstI Polymorphisms and Lung Cancer Risk in Chinese Population

  • Wang, Ya-Dong;Yang, Hai-Yan;Liu, Jing;Wang, Hai-Yu
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.13
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    • pp.5411-5416
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    • 2014
  • Background: A number of studies have reported relationships of CYP2E1 RsaI/PstI polymorphisms with susceptibility to lung cancer in Chinese population. However, the epidemiologic results have been conflictive rather than conclusive. The purpose of this study was to address the associations of CYP2E1 RsaI/PstI polymorphisms with lung cancer risk in Chinese population comprehensively. Materials and Methods: Systematic searches were conducted in the PubMed, Science Direct, Elsevier, CNKI and Chinese Biomedical Literature Databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of association. Results: Overall, we observed a decreased lung cancer risk among subjects carrying CYP2E1 RsaI/PstI c1/c2 and c1/c2+c2/c2 genotypes (OR=0.76, 95%CI: 0.64-0.90 and OR=0.78, 95%CI: 0.66-0.93, respectively), as compared with subjects carrying the c1/c1 genotype. In subgroup analysis, we observed a decreased lung cancer risk among c1/c2 carriers in hospital-based studies (OR=0.81, 95%CI: 0.68-0.98) and among carriers with c1/c2 and c1/c2+c2/c2 genotypes in population-based studies(OR=0.57, 95%CI: 0.42-0.79 and OR=0.58, 95%CI: 0.43-0.79, respectively), as compared with subjects carrying the c1/c1 genotype. Limiting the analysis to studies with controls in Hardy-Weinberg equilibrium (HWE), we similarly observed a decreased lung cancer risk among c1/c2 and c1/c2+c2/c2 carriers (OR=0.73, 95%CI: 0.60-0.88 and OR=0.73, 95%CI: 0.60-0.88, respectively), as compared with c1/c1. Conclusions: Our results suggested that CYP2E1 RsaI/PstI c1/c2 and c1/c2+c2/c2 variants might be a protective factor for developing lung cancer in Chinese population. Further well-designed studies with larger sample size are required to verify our findings.

Structure of $[cis-ReCl_4(py)(N-C_6H_3-2,6-i-Pr_2)\cdot(NH_2-C_6H_3-2,6-i-Pr_2)]$ (py=pyridine) ($[cis-ReCl_4(py)(N-C_6H_3-2,6-i-Pr_2)\cdot(NH_2-C_6H_3-2,6-i-Pr_2)]$ 착물의 구조(py=pyridine))

  • 최남선;이순원
    • Korean Journal of Crystallography
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    • v.10 no.2
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    • pp.105-109
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    • 1999
  • Ar 기류 하에서 Re(N-C6H3-2,6-i-Pr2)2Cl3(py) (1)과 propionaldehyde (C2H5CHO)가 반응하여 생성된 혼합물에서, [cis-ReCl4(py)(N-C6H3-2,6-i-Pr2)·(NH2-C6H3-2,6-i-Pr2)] (2)가 분리되었다. 이 화합물의 구조가 X-ray 회절법으로 규명되었다. 착물 2의 결정학 자료: 단사정계 공간군 P21/n, a=11.555(1) Å, b=27.066(3) Å, c=11.881(1) Å, β=117.991(8)°, Z=4, R(wR2)=0.0332(0.0851.

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Effects of camptothecin on the expression of DNA topoisomerase I and c-myc in HL-60 human leukemia cells (HL-60 사람 백혈병 세포에서 camptothecin이 DNA topoisomerase l과 c-myc의 발현에 미치는 영향)

  • 정인철;정대성;류경자;박장수;조무연
    • Journal of Life Science
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    • v.10 no.6
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    • pp.621-629
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    • 2000
  • Camptothecin (CPT) is an antitumor alkaloid that has been isolated from the Chinese tree, Camptotheca acuminata. The cytotoxicity of CPT has been correlated to its inhibition of DNA topoisomerase (Topo) I by stabilizing drug-enzyme-DNA “cleavable complex" resulting in DNA single-strand breaks and DNA-protein crosslinks. This studies were designed to elucidate whether CPT regulates Topo I mediated by CPT in DNAs containing c-myc protooncogene. We have conducted experiments on Topo I purification, pUC-MYC I cloning and Topo I assay using electrophoresis, quantitative RT-PCR and Northern blotting techniques. CPT ingibited the relaxation activity of Topo I in pUC19 DNA at various concentrations (1-1000 $\mu$M), while it enhanced the cleavage of Topo I in the pUC-MYC I by forming a cleavable complex at relatively high concentrations (100-1000 $\mu$M). In HL-60 cells treated with CPT, the expression of c-myc gene was decreased over that in the control group with no changes in the expression of Topo I mRNA. Our results suggest that Topo I is the target of CPT cytotoxicity but it does not affect Topo I extression, and the suppression of c-myc mRNA expression by CPT is due to c-myc damage resulted from formation of a cleavable complex with CPT. CPT.

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Insulin-Like Growth Factor-I-Induced Androgen Receptor Activation Is Mediated by the PI3K/Akt Pathway in C2C12 Skeletal Muscle Cells

  • Lee, Won Jun
    • Molecules and Cells
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    • v.28 no.5
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    • pp.495-499
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    • 2009
  • Although insulin-like growth factor-I (IGF-I) and androgen receptor (AR) are well known effectors of skeletal muscle, the molecular mechanism by which signaling pathways integrating AR and IGF-I in skeletal muscle cells has not been previously examined. In this study, the role of PI3K/Akt on IGF-I-induced gene expression and activation of AR in skeletal muscle cells was investigated. C2C12 cells were treated with IGF-I in the absence or presence of inhibitors of PI3K/Akt pathway (LY294002 and Wortmannin). Inhibition of the PI3K/Akt pathway with LY294002 or Wortmannin led to a significant decrease in IGF-I-induced AR phosphorylation and total AR protein expression. Furthermore, IGF-I-induced AR mRNA and skeletal ${\alpha}-actin$ mRNA were blocked by LY294002 or Wortmannin. Confocal images showed that IGF-I-induced AR translocation from cytosol to nucleus was inhibited significantly in response to treatment with LY294002 or Wortmannin. The present results suggest that modulating effect of IGF-I on AR gene expression and activation in C2C12 mouse skeletal muscle cells is mediated at least in part by the PI3K/Akt pathway.

Insulin-like Growth Factor-I Induces FATP1 Expression in C2C12 Myotubes (C2C12 myotube에서 Insulin-like growth factor-I 이 FATP1 발현에 미치는 영향)

  • Kim, Hye Jin;Lee, Won Jun
    • Journal of Life Science
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    • v.24 no.12
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    • pp.1284-1290
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    • 2014
  • Fatty acid transporter protein 1 (FATP1) is highly expressed in skeletal muscle and modulates fatty acid uptake and metabolism. However, the influence of insulin-like growth factor-I (IGF-I), a master regulator of skeletal muscle cells, on FATP1 in skeletal muscle cells has not been demonstrated. To investigate the effect of IGF-I on FATP1 and the expression of the IGFBP5 protein, differentiated C2C12 murine skeletal muscle cells were treated with 20 ng/ml of IGF-I at different time points. The results showed that IGF-I increased FATP1 and IGFBP5 protein expression in a time-dependent manner. To determine whether this induction of FATP1 by the IGF-I treatment was regulated pretranslationally, the mRNA level of FATP1 was measured by real-time quantitative PCR. The IGF-I treatment resulted in very rapid induction of the FATP1 mRNA transcript in C2C12 myotubes. FATP1 mRNA increased 169% and 132% after 24 and 48 h of the IGF-I treatment, respectively, and it returned to control levels after 72 h of the treatment, suggesting that the FATP1 gene is regulated pretranslationally by IGF-I in skeletal muscle cells. This is the first evidence that IGF-I can regulate the expression of FATP1. In conclusion, IGF-I induced rapid transcriptional modification of the FATP1 gene in C2C12 skeletal muscle cells and had modulating effects on fatty acid uptake proteins and oxidative proteins.