• Title/Summary/Keyword: ATF3

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Protective Effect of Borneolum on ER Stress-induced Damage in C6 Glial Cells (ER Stress에 의해 유발된 C6 Glial Cells의 손상에 대한 용뇌(龍腦)의 보호효과)

  • Jeon, In-Cheol;Bang, Chang-Ho;Moon, Byung-Soon;Lee, In
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.6
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    • pp.1368-1378
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    • 2009
  • Unfolded protein response (UPR) is an important genomic response to endoplasmic reticulum (ER) stress. The ER response is characterized by changes in specific proteins, induction of ER chaperones and degradation of misfolded proteins. Also, the pathogenesis of several diseases like Alzheimer's disease, neuronal degenerative diseases, and diabetes reveal the role of ER stress as one of the causative mechanisms. Borneolum has been used for neuronal disease in oriental medicine. In the present study, the protective effect of borneolum on thapsigargin-induced apoptosis in rat C6 glial cells. Treatment with C6 glial cells with 5 uM thapsigargin caused the loss of cell viability, and morphological change, which was associated with the elevation of intracellular $Ca^{++}$ level, the increase in Grp78 and CHOP and cleavage of pro-caspase 12 Furthermore, thapsigargin induced Grp98, XBP1, and ATF4 protein expression in C6 glial cells. Borneolum reduced thapsigargin-induced apoptosis through ER pathways. In the ER pathway, borneolum attenuated thapsigargin-induced elevations in Grp78, CHOP, ATF4, and XBP1 as well as reductions in pro-caspase 12 levels. Also, our data showed that borneolum protected thapsigargin-induced cytotoxicity in astrocytes from rat (P3) brain. Taken together, our data suggest that borneolum is neuroprotective against thapsigargin-induced ER stress in C6 glial cells and astrocytes. Accordingly, borneolum may be therapeutically useful for the treatment of thapsigargin-induced apoptosis in central nervous system.

Structural Design and Analysis upon Active Rotor Blade with Trailing-edge Flap (뒷전 플랩을 장착한 지능형 로터 블레이드의 구조 설계 및 해석)

  • Eun, Won-Jong;Natarajan, Balakumaran;Lee, Jae-Hwan;Shin, Sang-Joon
    • Journal of the Korean Society for Aeronautical & Space Sciences
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    • v.40 no.6
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    • pp.499-505
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    • 2012
  • Vibratory loads imposed by the rotating blade upon the fuselage has been one of major obstacles in rotorcrafts. A new concept of rotor blade is currently developed to adopt an Active Trailing-edge Flap (ATF) to alleviate such obstacles. The flap is mounted at 65~85% spanwise location from the rotor hub. The nominal rotational speed of the blade is as high as 1,528 RPM, to match the required tip Mach number. Structural integrity is one of the important design aspects to be maintained and monitored in this special type of rotor. This is due to that many detailed components, which drive the flap, are inserted inside the rotating blade. To conduct its structural design and analysis, CAMRAD-II and the one-dimensional beam analysis are used. At the same time, three-dimensional finite element analysis are also used, such as MSC. PATRAN/NASTRAN, in order to analyze the details of the present active blade. As a result, comparable characteristics for the present rotor are predicted by both approaches.

Effects of Lipopolysaccride-induced Stressor on the Expression of Stress-related Genes in Two Breeds of Chickens (Lipopolysaccride 감염처리가 닭의 품종간 스트레스연관 유전자 발현에 미치는 영향)

  • Jang, In Surk;Sohn, Sea Hwan;Moon, Yang Soo
    • Korean Journal of Poultry Science
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    • v.44 no.1
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    • pp.1-9
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    • 2017
  • The objective of the present study was to determine the expression of genes associated with lipopolysaccharide (LPS)-induced stressor in two breeds of chickens: the Korean native chicken (KNC) and the White Leghorn chicken (WLH). Forty chickens per breed, aged 40 weeks, were randomly allotted to the control (CON, administered the saline vehicle) and LPS-injected stress groups. Samples were collected at 0 and 48 h post-LPS injection, and total RNA was extracted from the chicken livers for RNA microarray and quantitative real-time polymerase chain reaction (qRT-PCR) analyses. In response to LPS, 1,044 and 1,193 genes were upregulated, and 1,000 and 1,072 genes were downregulated in the KNC and WLH, respectively, using a ${\geq}2$-fold cutoff change. A functional network analysis revealed that stress-related genes were downregulated in both KNC and WLH after LPS infection. The results obtained from the qRT-PCR analysis of mRNA expression of heat shock 90 (HSP90), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), activating transcription factor 4 (ATF4), sterol regulatory element-binding protein 1 (SREBP1), and X-box binding protein 1 (XBP1) were confirmed by the results of the microarray analysis. There was a significant difference in the expression of stress-associated genes between the control and LPS-injected KNC and WLH groups. The qRT-PCR analysis revealed that the stress-related $HSP90{\alpha}$ and HMGCR genes were downregulated in both LPS-injected KNC and WLH groups. However, the HSP70 and $HSP90{\beta}$ genes were upregulated only in the LPS-injected KNC group. The results suggest that the mRNA expression of stress-related genes is differentially affected by LPS stimulation, and some of the responses varied with the chicken breed. A better understanding of the LPS-induced infective stressors in chicken using the qRT-PCR and RNA microarray analyses may contribute to improving animal welfare and husbandry practices.

Expression of Beta-catenin-interacting Protein 1 (CTNNBIP1) Gene Is Increased under Hypothermia but Decreased under Additional Ischemia Conditions

  • Kwon, Kisang;Kim, Seung-Whan;Yu, Kweon;Kwon, O-Yu
    • Biomedical Science Letters
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    • v.20 no.3
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    • pp.168-172
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    • 2014
  • It has recently been shown that hypothermia treatment improves brain ischemia injury and is being increasingly considered by many clinicians. However, the precise roles of hypothermia for brain ischemia are not yet clear. In the present study we demonstrated firstly that hypothermia induced beta-catenin-interacting protein 1 (CTNNBIP1) gene expression and its expression was dramatically decreased under ischemic conditions. It was also demonstrated that hypothermia activated endoplasmic reticulum (ER) stress sensors especially both, the phosphorylation of $eIF2{\alpha}$, and ATF6 proteolytic cleavage. However, the factors of apoptosis and autophagy were not associated with hypothermia. These findings suggested that hypothermia controlled CTNNBIP1 gene expression under ischemia, which may provide a clue to the development of treatments and diagnostic methods for brain ischemia.

Insights into the signal transduction pathways of mouse lung type II cells revealed by transcription factor profiling in the transcriptome

  • Ramana, Chilakamarti V.
    • Genomics & Informatics
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    • v.17 no.1
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    • pp.8.1-8.10
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    • 2019
  • Alveolar type II cells constitute a small fraction of the total lung cell mass. However, they play an important role in many cellular processes including trans-differentiation into type I cells as well as repair of lung injury in response to toxic chemicals and respiratory pathogens. Transcription factors are the regulatory proteins dynamically modulating DNA structure and gene expression. Transcription factor profiling in microarray datasets revealed that several members of AP1, ATF, $NF-{\kappa}B$, and C/EBP families involved in diverse responses were expressed in mouse lung type II cells. A transcriptional factor signature consisting of Cebpa, Srebf1, Stat3, Klf5, and Elf3 was identified in lung type II cells, Sox9+ pluripotent lung stem cells as well as in mouse lung development. Identification of the transcription factor profile in mouse lung type II cells will serve as a useful resource and facilitate the integrated analysis of signal transduction pathways and specific gene targets in a variety of physiological conditions.

Anti-adipogenic, Anti-inflammatory, and Anti-proliferative Activities of Extracts from Lees and Nuruk (주박과 누룩의 추출물에 의한 지방세포형성억제, 항염증 및 항성장 활성)

  • Son, Jung-Bin;Lee, Seung Hoon;Sohn, Ho-Yong;Shin, Woo-Chang;Kim, Jong-Sik
    • Journal of Life Science
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    • v.25 no.7
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    • pp.773-779
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    • 2015
  • This study examined extracts from five different kinds of lees and nuruk and their organic solvent fractions in terms of several biological functions, such as anti-adipogenic, anti-inflammatory, and anti-proliferative activities. The anti-adipogenic activity was investigated by treating mouse pre-adipocyte 3T3-L1 cells with one extract (YE) and four organic solvent fractions (YAc, PAc, RAc, and WPAc) during adipogenesis. Among the treated samples, the ethyl acetate fraction of W-Ju lees (WPAc) showed the strongest anti-adipogenic effect, which was confirmed with oil red O staining and down-regulation of pro-adipogenic genes such as PPAR-gamma and SCD-1. Treatment with WPAc also reduced the expression of PPAR-gamma in a time-dependent manner. The effects of five different extracts were examined on nitric oxide (NO) production in mouse RAW 264.7 cells to determine anti-inflammatory activity. The ethyl acetate fraction of B-Ju lees (PAc) significantly decreased NO production in LPS-stimulated RAW 264.7 cells and it also inhibited NO production in a dose-dependent manner. The PAc fraction also dramatically decreased the viability of human colorectal cancer HCT116 cells in a dose-dependent manner. In addition, PAc increased the expression of NAG-1 and ATF3 genes in a dose dependent manner. Overall, these results indicate that lees and nuruk have several biological functions, including anti-adipogenic, anti-inflammatory, and anti-proliferative activities.

Synergistic Cytotoxic Effects by Combination Treatment of Genistein and Daidzein in Human Colorectal Cancer Cell (대장암 세포주에서 genistein과 daidzein의 병합처리에 의한 상승적인 세포독성 효과)

  • Son, Seong-Min;Lim, Seung-Hyun;Kim, Hyo-Rim;Kim, Min-Jeong;Kim, Tae-Wan;Lee, Jong-Hwa;Kim, Jong-Sik
    • Journal of Life Science
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    • v.19 no.9
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    • pp.1294-1298
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    • 2009
  • To investigate whether isoflavone genistein and daidzein could affect cancer cell viability, human colorectal HCT116 cells were incubated with genistein or daidzein in a dose-dependent manner. Genistein decreased cancer cell viability in a dose-dependent manner, whereas daidzein did not show dramatic cytotoxic effects. We also found that 71 genes were up-regulated more than 2-fold, whereas 64 genes were down-regulated more than 2-fold with 24 hr of $50{\mu}M$ genistein treatment by our previous microarray data. Among the up-regulated genes, we selected 3 genes (DKK1, ATF3 and NAG-1) and performed RT-PCR to confirm microarray data. The results of RT-PCR were highly correlated with those of the microarray experiment. In addition, we investigated whether a combination treatment of genistein and daidzein could affect cancer cell viability. Surprisingly, the combination treatment did show synergistic cytotoxic effects detected by MTS assay. The results of RT-PCR and real-time PCR indicate that a combination of genistein and daidzein can synergistically induce NAG-1 expression in HCT116 cells. This result implies that NAG-1 induction is highly associated with synergistic cytotoxic effects induced by a combination treatment of genistein and daidzein. Overall, these results may provide a clue in explaining the anti-cancer activity of soy bean in human colorectal cancer.

Molecular mechanism of protopanaxadiol saponin fraction-mediated anti-inflammatory actions

  • Yang, Yanyan;Lee, Jongsung;Rhee, Man Hee;Yu, Tao;Baek, Kwang-Soo;Sung, Nak Yoon;Kim, Yong;Yoon, Keejung;Kim, Ji Hye;Kwak, Yi-Seong;Hong, Sungyoul;Kim, Jong-Hoon;Cho, Jae Youl
    • Journal of Ginseng Research
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    • v.39 no.1
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    • pp.61-68
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    • 2015
  • Background: Korean Red Ginseng (KRG) is a representative traditional herbal medicine with many different pharmacological properties including anticancer, anti-atherosclerosis, anti-diabetes, and anti-inflammatory activities. Only a few studies have explored the molecular mechanism of KRG-mediated anti-inflammatory activity. Methods: We investigated the anti-inflammatory mechanisms of the protopanaxadiol saponin fraction (PPD-SF) of KRG using in vitro and in vivo inflammatory models. Results: PPD-SF dose-dependently diminished the release of inflammatory mediators [nitric oxide (NO), tumor necrosis factor-${\alpha}$, and prostaglandin $E_2$], and downregulated the mRNA expression of their corresponding genes (inducible NO synthase, tumor necrosis factor-${\alpha}$, and cyclooxygenase-2), without altering cell viability. The PPD-SF-mediated suppression of these events appeared to be regulated by a blockade of p38, c-Jun N-terminal kinase (JNK), and TANK (TRAF family member-associated NF-kappa-B activator)-binding kinase 1 (TBK1), which are linked to the activation of activating transcription factor 2 (ATF2) and interferon regulatory transcription factor 3 (IRF3). Moreover, this fraction also ameliorated HCl/ethanol/-induced gastritis via suppression of phospho-JNK2 levels. Conclusion: These results strongly suggest that the anti-inflammatory action of PPD-SF could be mediated by a reduction in the activation of p38-, JNK2-, and TANK-binding-kinase-1-linked pathways and their corresponding transcription factors (ATF2 and IRF3).

Design of The Two-Stage Low Noise Amplifier for IMT-2000 Base Stations (IMT-2000 기지국용 저잡음 증폭기 설계)

  • 배영수;최재훈
    • Proceedings of the Korea Electromagnetic Engineering Society Conference
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    • 2001.11a
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    • pp.252-256
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    • 2001
  • 본 논문에서는 IMT-2000 기지국용 2단 저잡음 증폭기를 설계했다. 잡음지수 특성이 뛰어난 HP사의 PHEMT 소자인 ATF-35143을 사용하였고 능동소자의 바이어스는 $V_{ds}$ 가 3 v $I_{d}$을 30mA로 설정했다. 첫 단은 최소잡음 지수에 중점을 두고 설계했고 둘째 단은 이득에 초점을 맞추어 설계했다. 입출력 정재파 비를 줄이기 위해서 전체증폭기의 앞단과 뒷단에 삽입손실이 0.2dB인 X503 SMT 90도 하이브리드 커플러를 설치 했다. 제작을 위해 기판은 두께 0.76mm이고 비유전율 4.2의 FR-4를 사용했다. 설계된 저잡음 증폭기의 특성은 주파수대역 1.92GHz~1.98GHz에서 잡음지수 0.45dB, 입출력 정재파 비 1.2이하, 이득은 32dB이상의 특성을 보였다.

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Regulation of Cyclic AMP-Response Element Binding Protein Zhangfei (CREBZF) Expression by Estrogen in Mouse Uterus

  • Jang, Hoon
    • Development and Reproduction
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    • v.22 no.1
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    • pp.95-104
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    • 2018
  • CREBZF (cAMP-response element binding protein zhangfei) is a member of ATF/CREB family, and which regulates various cellular functions by suppressing major factors with direct interaction. In this study, we have examined the expression of CREBZF on mouse endometrium during uterus estrous cycles and estrogen (E2) treatment. In uterus, CREBZF mRNA expression was higher than other organs and mRNA and protein of CREBZF was increased in proestrus phase and decreased in estrus phase. The expression of CREBZF in 3-weeks old mouse uterus was reduced by E2 injection in endometrium. In addition, the expression of progesterone receptor, a marker of E2 in ovariectomized mice was found to be strongly expressed in stroma, while CREBZF was only expressed in epithelium. Also, we conformed that E2-suppressed CREBZF was restored by co-injection of ICI 182,780, an estrogen receptor antagonist. Overall, these results suggest that CREBZF is regulated by estrogen and involved in ER signaling pathway in mouse uterus.