• Title/Summary/Keyword: mechanism study

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Insulin-Like Growth Factor-I Induces Androgen Receptor Coactivator Expression in Skeletal Muscle Cells through the p38 MAPK and ERK1/2 Pathways (C2C12 세포에서 insulin-like growth factor-I이 p38 MAPK, ERK1/2 신호전달 경로를 통해 엔드로젠 수용체 coactivator 발현에 미치는 영향)

  • Park, Chan-Ho;Kim, Hye-Jin;Kim, Tae-Un;Lee, Won-Jun
    • Journal of Life Science
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    • v.21 no.2
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    • pp.242-250
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    • 2011
  • Although insulin-like growth factor-I (IGF-I) and androgen receptor (AR) coactivators are well known effectors of skeletal muscle, the molecular mechanism by which signaling pathways integrating AR coactivators and IGF-I in skeletal muscle cells has not been previously examined. In this study, the effects of IGF-I treatment on the gene expression of AR coactivators in the absence of AR ligands and the roles of the p38 MAPK and ERK1/2 signaling pathways in IGF-I-induced AR coactivators induction were examined. C2C12 cells were treated with 250 ng/ml of IGF-I in the presence or absence of specific inhibitors p38 MAPK (SB203580) or ERK1/2 (PD98059). Treatment of C2C12 cells with IGF-I resulted in increased in GRIP-1, SRC-1, and ARA70 protein expression. The levels of GRIP-1, SRC-1, and ARA70 mRNA were also significantly increased after 5min of IGF-I treatment. IGF-I-induced AR coactivator proteins were significantly blocked by pharmacological inhibitors of p38 MAPK and ERK1/2 pathways. However, there was no significant effect of those inhibitors on IGF-I-induced mRNA level of AR coactivators, suggesting that AR coactivators are post-transcriptionally regulated by IGF-I. Furthermore, the present results suggest that IGF-I stimulates the expression of AR coactivators by cooperative activation of the p38 MAPK and ERK1/2 pathways in C2C12 mouse skeletal muscle cells.

Sphingosine-1-Phosphate-Induced Migration and Differentiation of Human Mesenchymal Stem Cells to Smooth Muscle Cells (Sphingosine-1-phosphate에 의한 중간엽 줄기세포의 이동과 평활근세포로의 분화)

  • Song, Hae-Young;Shin, Sang-Hun;Kim, Min-Young;Kim, Jae-Ho
    • Journal of Life Science
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    • v.21 no.2
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    • pp.183-193
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    • 2011
  • Migration and differentiation of mesenchymal stem cells are crucial for tissue regeneration in response to injury. Sphingosine-1-phosphate (S1P) is a bioactive lipid that regulates a variety of biological processes, including proliferation, survival, differentiation and motility. In the present study, we determined the role of S1P in migration and differentiation of human bone marrow-derived mesenchymal stem cells (BMSCs). S1P stimulated migration of BMSCs in a dose- and time-dependent manner, and pre-incubation of the cells with pertussis toxin completely abrogated S1P-induced migration, suggesting involvement of Gi-coupled receptors in S1P-induced cell migration. S1P elicited elevation of intracellular concentration of $Ca^{2+}$ ($[Ca^{2+}]_i$) and pretreatment with VPC23019, an antagonist of $S1P_1/S1P_3$, blocked S1P-induced migration and increase of $[Ca^{2+}]_i$. Small interfering RNA-mediated knockdown of endogenous $S1P_1$ attenuated S1P-induced migration of BMSCs. Furthermore, S1P treatment induced expression of $\alpha$-smooth muscle actin ($\alpha$-SMA), a smooth muscle marker, and pretreatment with VPC23019 abrogated S1P-induced $\alpha$-SMA expression. S1P induced phosphorylation of p38 mitogen-activated protein kinase (MAPK), and pretreatment of cells with SB202190, an inhibitor of p38 MAPK, or adenoviral overexpression of a dominant-negative mutant of the p38 MAPK blocked S1P-induced cell migration and $\alpha$-SMA expression. Taken together, these results suggest that S1P stimulates migration and smooth muscle differentiation of BMSCs through an $S1P_1$-p38 MAPK-dependent mechanism.

Characterization of HtrA2-deficient Mouse Embryonic Fibroblast Cells Based on Morphology and Analysis of their Sensitivity in Response to Cell Death Stimuli. (HtrA2 유전자가 결손된 mouse embryonic fibroblast 세포주의 형태학적 특징 및 세포사멸 자극에 대한 감수성 조사)

  • Lee, Sang-Kyu;Nam, Min-Kyung;Kim, Goo-Young;Rhim, Hyang-Shuk
    • Journal of Life Science
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    • v.18 no.4
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    • pp.522-529
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    • 2008
  • High-temperature requirement A2(HtrA2) has been known as a human homologue of bacterial HtrA that has a molecular chaperone function. HtrA2 is mitochondrial serine protease that plays a significant role in regulating the apoptosis; however, the physiological function of HtrA2 still remains elusive. To establish experimental system for the investigation of new insights into the function of HtrA2 in mammalian cells, we first obtained $HtrA2^{+/+}$ and $HtrA2^{-/-}$ MEF cells lines and identified those cells based on the expression pattern and subcellular localization of HtrA2, using immunoblot and biochemical assays. Additionally, we observed that the morphological characteristics of $HtrA2^{-/-}$ MEF cells are different form those of $HtrA2^{+/+}$ MEF cells, showing a rounded shape instead of a typical fibroblast-like shape. Growth rate of $HtrA2^{-/-}$ MEF cells was also 1.4-fold higher than that of $HtrA2^{+/+}$ MEF cells at 36 hours. Furthermore, we verified both MEF cell lines induced caspsase-dependent cell death in response to apoptotic stimuli such as heat shock, staurosporine, and rotenone. The relationship between HtrA2 and heat shock-induced cell death is the first demonstration of the research field of HtrA2. Our study suggests that those MEF cell lines are suitable reagents to further investigate the molecular mechanism by which HtrA2 regulates the balance between cell death and survival.

Spatial Genetic Structure at a Korean Pine (Pinus koraiensis) Stand on Mt. Jumbong in Korea Based on Isozyme Studies (점봉산(點鳳山) 잣나무임분(林分)의 개체목(個體木) 공간분포(空間分布)에 따른 유전구조(遺傳構造))

  • Hong, Kyung-Nak;Kwon, Young-Jin;Chung, Jae-Min;Shin, Chang-Ho;Hong, Yong-Pyo;Kang, Bum-Yong
    • Journal of Korean Society of Forest Science
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    • v.90 no.1
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    • pp.43-54
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    • 2001
  • Genetic differentiation of populations is resulted from the environmental and the genetic effects, and the interactions between them. Whereas, the major factors influencing to the genetic differentiation within populations are the gene flow induced by seed or pollen dispersial, the microsite heterogeneity, and the density-dependent distribution of individuals. For the purpose of studying spatial genetic structure and the distribution pattern of Korean pines(Pinus koraiensis), we set up one $100{\times}100m$ plot at a Korean pine stand in Quercus mongolica community on Mt. Jumbong in Korea. To estimate the coefficient of spatial autocorrelation as Moran's index and an analogue, simple block distance, isozyme markers were analyzed in 325 Korean pines. For 11 polymorphic loci observed in 9 enzyme systems, the average percentage of polymorphic loci, the observed and expected heterozygocity were 72.2% 0.200, and 0.251, respectively. It was revealed the excess of homozygotes was observed in the plot, which suggests that here may be more number of consanguineous trees than expected. On the basis of isozyme genotypes observed in this study, 325 trees were classified into 147 groups in which the maximum number of trees for one group was 34. From the distance class of 24-32m, the genetic heterogeneity began to increase. The variation of simple block distance against the growth performance by tree height and diameter also showed the same trend at 24~32m class. According to high fixation index(F=0.204), the spatial genetic structure within a stand, the analysis of the growth performance, and the distribution patterns of identical genotypes, we inferred that the genetic structure of a Korean pine stand in Mt. Jumbong has been maintained rather density-dependent mechanism than the gene flow, such as the pollen dispersial or the heavy input of seeds following the forest gaps. The genetic patchy size was determined between 24~32m, which suggests that the selection of individuals for the ex situ conservation of Korean pine in Mt. Jumbong may be desirable to be made with the spatial distance over 37 meters between trees.

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Clinical Significance of Antibodies Against Platelet HLA Class I in Children with Idiopathic Thrombocytopenic Purpura (소아 특발성 혈소판 감소증에서 항-HLA Class I항체의 임상적 의미)

  • Lee, Hong Jun;Yeom, Jung-Sook;Park, Ji Sook;Park, Eun Sil;Seo, Ji-Hyun;Lim, Jae Young;Park, Chan-Hoo;Woo, Hyang-Ok;Youn, Hee-Shang
    • The Korean Journal of Blood Transfusion
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    • v.24 no.3
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    • pp.233-240
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    • 2013
  • Background: A previous history of transfusion has been known to be associated with production of anti-HLA class I antibodies. However, platelet glycoproteins are the main target of idiopathic thrombocytopenic purpura (ITP). The mechanism of antibody production is known to differ significantly between glycoproteins and anti-HLA class I. The aim of this study was to evaluate the clinical significance of anti-HLA class I antibodies in childhood ITP. Methods: Enrollment for the normal control group targeted 48 people who visited Gyeongsang National University Hospital from 1990 to 2010, and 48 young children with ITP. Anti-glycoproteins and anti-HLA class I antibodies were tested using the Modified Antigen Capture Enzyme-linked immunosorbent assay (MACE) kit. Results: The positive rate of anti-HLA antibodies was significantly different [36/39 (92.3%) vs 29/46 (63%)] [ITP group vs normal control group] (P=0.002). The mean positive S/C ratio of anti-HLA antibodies was also significantly different (3.55 vs 1.51) [ITP group vs normal control group] (P=0.0000). The positive rate of anti-HLA did not differ significantly between the transfused group and the non-transfused group [12/12 (100%) vs 24/27 (88%)] [transfused ITP vs non-transfused ITP]. The mean positive S/C ratio of anti-HLA antibodies did not differ significantly between the transfused ITP group and the non-transfused ITP group (4.30 vs 3.25) [transfused ITP vs non-transfused ITP]. Consecutive testing showed that positive rate and positive S/C ratio of anti-HLA antibodies did not change significantly between sampling times in both groups [transfused ITP vs non-transfused ITP] (P=1.00 and P=0.15). Conclusion: Anti-HLA class I antibodies may be involved in childhood ITP. Transfusion did not affect the course of childhood ITP.

Improvement of Energy Density in Supercapacitor by Ion Doping Control for Energy Storage System (에너지 저장장치용 슈퍼커패시터 이온 도핑 제어를 통한 에너지 밀도 향상 연구)

  • Park, Byung-jun;Yoo, SeonMi;Yang, SeongEun;Han, SangChul;No, TaeMoo;Lee, Young Hee;Han, YoungHee
    • KEPCO Journal on Electric Power and Energy
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    • v.5 no.3
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    • pp.209-213
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    • 2019
  • Recently, demand for high energy density and long cycling stability of energy storage system has increased for application using with frequency regulation (F/R) in power grid. Supercapacitor have long lifetime and high charge and discharge rate, it is very adaptable to apply a frequency regulation in power grid. Supercapacitor can complement batteries to reduce the size and installation of batteries. Because their utilization in a system can potentially eliminate the need for short-term frequent replacement as required by batteries, hence, saving the resources invested in the upkeep of the whole system or extension of lifecycle of batteries in the long run of power grid. However, low energy density in supercapacitor is critical weakness to utilization for huge energy storage system of power grid. So, it is still far from being able to replace batteries and struggle in meeting the demand for a high energy density. But, today, LIC (Lithium Ion Capacitor) considered as an attractive structure to improve energy density much more than EDLC (Electric double layer capacitor) because LIC has high voltage range up to 3.8 V. But, many aspects of the electrochemical performance of LIC still need to be examined closely in order to apply for commercial use. In this study, in order to improve the capacitance of LIC related with energy density, we designed new method of pre-doping in anode electrode. The electrode in cathode were fabricated in dry room which has a relative humidity under 0.1% and constant electrode thickness over $100{\mu}m$ was manufactured for stable mechanical strength and anode doping. To minimize of contact resistance, fabricated electrode was conducted hot compression process from room temperature to $65^{\circ}C$. We designed various pre-doping method for LIC structure and analyzing the doping mechanism issues. Finally, we suggest new pre-doping method to improve the capacitance and electrochemical stability for LIC.

Effect of Halophilic Bacterium, Haloarcula vallismortis, Extract on UV-induced Skin Change (호염 미생물(Haloarcula vallismortis) 용해물의 자외선유발 피부변화에 대한 효과)

  • Kim, Ji Hyung;Shin, Jae Young;Hwang, Seung Jin;Kim, Yun Sun;Kim, Yoo Mi;Gil, So Yeon;Jin, Mu Hyun;Lee, Sang Hwa
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.41 no.4
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    • pp.341-350
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    • 2015
  • Skin carrys out protective role against harmful outer environment assaults including ultraviolet radiation, heavy metals and oxides. Especially, ultraviolet-B (UVB) light causes inflammatory reactions in skin such as sun burn and erythma and stimulates melanin pigmentation. Furthermore, the influx of UVB into skin cells causes DNA damage in keratinocytes and dermal fibroblasts, inhibition of extracellular matrix (ECM) synthesis which leads to a decrease in elasticity of skin and wrinkle formation. It also damages dermal connective tissue and disrupts the skin barrier function. Prolonged exposure of human skin to UVB light is well known to trigger severe skin lesions such as cell death and carcinogenesis. Haloarcula vallismortis is a halophilic microorganism isolated from the Dead Sea, Its growth characteristics have not been studied in detail yet. It generally grows at salinity more than 10%, but the actual growth salinity usually ranges between 20 to 25%. Because H. vallismortis is found mainly in saltern or salt lakes, there could exist defense mechanisms against strong sunlight. One of them is generation of additional ATP using halorhodopsin which absorbs photons and produces energy by potential difference formed by opening the chloride ion channel. It often shows a color of pink or red because of their high content of carotenoid pigments and it is considered to act as a defense mechanism against intense UV irradiation. In this study, the anti-inflammatory effect of the halophilic microorganism, H. vallismortis, extract was investigated. It was found that H. vallismortis extract had protective effect on DNA damage induced by UV irradiation. These results suggest that the extract of halophilic bacterium, H. vallismortis could be used as a bio-sunscreen or natural sunscreen which ameliorate the harmful effects of UV light with its anti-inflammatory and DNA protective properties.

Antioxidants and Anti-obesity Activities of Hot Water and Ethanolic Extracts from Cheonnyuncho (Opuntia humifusa) (천년초의 열수 및 에탄올 추출물의 항산화 및 항비만 활성)

  • Kim, Dae-Jung;Jung, Ji-Hoon;Kim, Sun-Gu;Lee, Hya-Ku;Lee, Seong-Kap;Hong, Hee-Do;Lee, Boo-Yong;Lee, Ok-Hwan
    • Food Science and Preservation
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    • v.18 no.3
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    • pp.366-373
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    • 2011
  • Recent studies suggested that Cheonnyuncho is a significant source of bioactive phenolic compounds, comparable to phytochemicals, including green tea and onion. In this study, the hot-water and 80% ethanolic extracts of Cheonnyuncho were assessed as to their total phenol content, total flavonoids content, antioxidant activity (DPPH radical-scavenging activity and reducing power), and anti-obesity activity. The results showed that the total phenol contents of the hot water extract and the 80% ethanolic extract were $16.52{\pm}3.87$ and $13.44{\pm}0.85$ mg GAE/g, respectively. The total flavonoids content was detected only in the 80% ethanolic extract, however, with a 778.08 ${\mu}g$ catechin equivalents/g content. The DPPH radical-scavenging activity and reducing power of the 80% ethanolic extract from Cheonnyuncho was significantly higher than those of the water extract (p < 0.05). During the adipocyte differentiation, the 80% ethanolic extract of Cheonnyuncho more significantly inhibited lipid accumulation and ROS production than the 3T3-L1 cells that were treated with hot water extract. Furthermore, the 80% ethanolic extract of Cheonnyuncho suppressed the mRNA abundance of the adipogenic transcription factor, $PPAR{\gamma}$ (peroxisome proliferator-activated receptor ${\gamma}$), and its target gene, aP2 (adipocyte protein 2). These results indicate that Cheonnyuncho extracts can inhibit adipogenesis through a mechanism that involves direct down regulation of $PPAR{\gamma}$ gene expression or via modulation of ROS production associated with radical-scavenging activities.

Design of accelerated life test on temperature stress of piezoelectric sensor for monitoring high-level nuclear waste repository (고준위방사성폐기물 처분장 모니터링용 피에조센서의 온도 스트레스에 관한 가속수명시험 설계)

  • Hwang, Hyun-Joong;Park, Changhee;Hong, Chang-Ho;Kim, Jin-Seop;Cho, Gye-Chun
    • Journal of Korean Tunnelling and Underground Space Association
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    • v.24 no.6
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    • pp.451-464
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    • 2022
  • The high-level nuclear waste repository is a deep geological disposal system exposed to complex environmental conditions such as high temperature, radiation, and ground-water due to handling spent nuclear fuel. Continuous exposure can lead to cracking and deterioration of the structure over time. On the other hand, the high-level nuclear waste repository requires an ultra-long life expectancy. Thus long-term structural health monitoring is essential. Various sensors such as an accelerometer, earth pressure gauge, and displacement meter can be used to monitor the health of a structure, and a piezoelectric sensor is generally used. Therefore, it is necessary to develop a highly durable sensor based on the durability assessment of the piezoelectric sensor. This study designed an accelerated life test for durability assessment and life prediction of the piezoelectric sensor. Based on the literature review, the number of accelerated stress levels for a single stress factor, and the number of samples for each level were selected. The failure mode and mechanism of the piezoelectric sensor that can occur in the environmental conditions of the high-level waste repository were analyzed. In addition, two methods were proposed to investigate the maximum harsh condition for the temperature stress factor. The reliable operating limit of the piezoelectric sensor was derived, and a reasonable accelerated stress level was set for the accelerated life test. The suggested methods contain economical and practical ideas and can be widely used in designing accelerated life tests of piezoelectric sensors.

Effect and mechanism of chitosan-based nano-controlled release system on the promotion of cell cycle progression gene expression (키토산 기반 나노방출제어시스템의 세포주기진행 유전자 발현 증진 효과 및 기전)

  • Lee, Won Joong;Park, Kwang Man;Lee, sungbok Richard;Hwang, Yu Jeong;Lee, Suk Won
    • The Journal of Korean Academy of Prosthodontics
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    • v.59 no.4
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    • pp.379-394
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    • 2021
  • Purpose. In our previous studies, application of trichloroacetic acid (TCA) to gingival fibroblasts or to canine palatal soft tissue was verified to alter the expression of several genes responsible for cell cycle progression. In order to confirm this effect in a system allowing sequential release of TCA and epidermal growth factor (EGF), expression of various cell cycle genes following the application of the agents, using hydrophobically modified glycol chitosan (HGC)-based nano-controlled release system, was explored in this study. Materials and methods. HGC-based nano-controlled release system was developed followed by loading TCA and EGF. The groups were defined as the control (CON); TCA-loaded nano-controlled release system (EXP1); TCA- and EGF- individually loaded nano-controlled release system (EXP2). At 24- and 48 hr culture, expression of 37 cell cycle genes was analyzed in human gingival fibroblasts. Correlations and the influential genes were also analyzed. Results. Numerous genes such as cyclins (CCNDs), cell division cycles (CDCs), cyclin-dependent kinases (CDKs), E2F transcription factors (E2Fs), extracellular signal-regulated kinases (ERKs) and other cell cycle genes were significantly up-regulated in EXP1 and EXP2. Also, cell cycle arrest genes of E2F4, E2F5, and GADD45G were up-regulated but another cell cycle arrest gene SMAD4 was down-regulated. From the multiple regression analysis, CCNA2, CDK4, and ANAPC4 were determined as the most influential factors on the expression of ERK genes. Conclusion. Application of TCA and EGF, using the HGC-based nano-controlled sequential release system significantly up-regulated various cell cycle progression genes, leading to the possibility of regenerating oral soft tissue via application of the proposed system.