• Title/Summary/Keyword: down-regulation

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Glucocorticoid Receptor Induced Down Regulation of Metalloproteinase-9 (bfMP-9) by Ginseng Components, Panaxadiol (PD) and Panaxatriol (PT), Contributes to Inhibition of the Invasive Capacity of HTl080 Human Fibrosarcoma Cells

  • Park, Moon-Taek;Cha, Hee-Jae;Jeong, Joo-Won;Kim, Shin-Il;Kim, Kyu-Won
    • Proceedings of the Ginseng society Conference
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    • 1998.06a
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    • pp.224-230
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    • 1998
  • This study showed the anti-invasive activity of ginseng components, panaxadiol (PD) and panamatrlol (PT) on the highly metastatic HT1080 human flbrosarcoma cell line. PD and PT reduced tumor cell invasion through a reconstitute basement membrane in the transwell chamber. A significant down regulation of MMP-9 by PD and PT was detected by northern blot analysis. However, MMP-2 was constantly expressed. Quantitative gelatin based zymography confirmed a marked reduced expression of MMP-9 but not MMP-2 in the treatment of PD and PT. Since the chemical structures of PD and PT are very similar to that of dexamethasone, a synthetic glucocorticoid, it was investigated whether PD and PT act through GR. Western blot analysis and immunocytochemistry showed that PD and PT increased the GR fraction in the nucleus. These results suggest that ursolic acid may induce repression of MMP-9 by stimulating the nuclear translocation of GR and hence inhibiting the activity of AP-1 to TPA-responsible element of MMP-9 promoter region. In conclusion, we suggest that CR-induced down-regulation of MMP-9 by PD and PT contributes to reduce the invasive capacity of HT 1080 cells.

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Cobalt Chloride-Induced Down-Regulation of Puromycin-Sensitive Aminopeptidase Involved in Apoptosis of PC-3 Cells (PC-3 세포에서 cobalt chloride에 의해 down-regulation되는 puromycin-sensitive aminopeptidase의 apoptosis에 미치는 효과)

  • Lee, Suk-Hee;Kim, Hwan-Gyu
    • Journal of Life Science
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    • v.20 no.7
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    • pp.991-998
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    • 2010
  • Hypoxia is an indicative of pro-apoptotic and anti-apoptotic biphasic effects, which appear to be dependent upon the cell type and the condition of the cells. The hypoxia-mimetic agent, cobalt chloride ($CoCl_2$), has been shown to induce apoptosis in a variety of cell types, but the mechanism by which this occurs has yet to be thoroughly elucidated. Puromycin-sensitive aminopeptidase (PSA) gene was decreasingly expressed in response to $CoCl_2$. In this report, puromycin pretreatment applied to PC-3 cells resulted in apoptosis. To determine whether PSA is involved in apoptosis, we examined the apoptotic properties of the PC-3 cells after siRNA knockdown of PSA. PSA siRNA-induced PSA silencing revealed that endogenous PSA may be involved in apoptosis of the PC-3 cells. These results indicated that PSA may perform a vital function in cell survival of the PC-3 cells.

Let-7c miRNA Inhibits the Proliferation and Migration of Heat-Denatured Dermal Fibroblasts Through Down-Regulating HSP70

  • Jiang, Tao;Wang, Xingang;Wu, Weiwei;Zhang, Fan;Wu, Shifeng
    • Molecules and Cells
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    • v.39 no.4
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    • pp.345-351
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    • 2016
  • Wound healing is a complex physiological process necessitating the coordinated action of various cell types, signals and microRNAs (miRNAs). However, little is known regarding the role of miRNAs in mediating this process. In the present study, we show that let-7c miRNA is decreased in heat-denatured fibroblasts and that inhibiting let-7c expression leads to the increased proliferation and migration of dermal fibroblasts, whereas the overexpression of let-7c exerts an opposite effect. Further investigation has identified heat shock protein 70 as a direct target of let-7c and has demonstrated that the expression of HSP70 in fibroblasts is negatively correlated with let-7c levels. Moreover, down-regulation of let-7c expression is accompanied by up-regulation of Bcl-2 expression and down-regulation of Bax expression, both of which are the downstream genes of HSP70. Notably, the knockdown of HSP70 by HSP70 siRNA apparently abrogates the stimulatory effect of let-7c inhibitor on heat-denatured fibroblasts proliferation and migration. Overall, we have identified let-7c as a key regulator that inhibits fibroblasts proliferation and migration during wound healing.

SOCS3 Attenuates Dexamethasone-Induced M2 Polarization by Down-Regulation of GILZ via ROS- and p38 MAPK-Dependent Pathways

  • Hana Jeong;Hyeyoung Yoon;Yerin Lee;Jun Tae Kim;Moses Yang;Gayoung Kim;Bom Jung;Seok Hee Park;Choong-Eun Lee
    • IMMUNE NETWORK
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    • v.22 no.4
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    • pp.33.1-33.17
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    • 2022
  • Suppressors of cytokine signaling (SOCS) have emerged as potential regulators of macrophage function. We have investigated mechanisms of SOCS3 action on type 2 macrophage (M2) differentiation induced by glucocorticoid using human monocytic cell lines and mouse bone marrow-derived macrophages. Treatment of THP1 monocytic cells with dexamethasone (Dex) induced ROS generation and M2 polarization promoting IL-10 and TGF-β production, while suppressing IL-1β, TNF-α and IL-6 production. SOCS3 over-expression reduced, whereas SOCS3 ablation enhanced IL-10 and TGF-β induction with concomitant regulation of ROS. As a mediator of M2 differentiation, glucocorticoid-induced leucine zipper (GILZ) was down-regulated by SOCS3 and up-regulated by shSOCS3. The induction of GILZ and IL-10 by Dex was dependent on ROS and p38 MAPK activity. Importantly, GILZ ablation led to the inhibition of ROS generation and anti-inflammatory cytokine induction by Dex. Moreover, GILZ knock-down negated the up-regulation of IL-10 production induced by shSOCS3 transduction. Our data suggest that SOCS3 targets ROS- and p38-dependent GILZ expression to suppress Dex-induced M2 polarization.

A Study on the Inspection and Certification System of Organic Production of Agricultural Products and Foodstuffs in EU - Germany - (EU의 유기농식품 검인증시스템 연구 -독일을 중심으로-)

  • Yoo, Duck-Ki
    • Korean Journal of Organic Agriculture
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    • v.16 no.1
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    • pp.59-89
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    • 2008
  • The Council Regulation (EEC) No 2092/91 of 24 Juni 1991 on organic production of agricultural products and indications referring thereto on agricultural products and foodstuffs. This Regulation describes the legal framework for agricultural products and foodstuffs obtained organically. The Regulation establishes a harmonized framework for the production, labelling and inspection of agricultural products and foodstuffs in order to increase consumer confidence in such products and ensure fair competition between producers. This article presents a study about inspection and certification system of organic production of agricultural products and foodstuffs in Germany. In order to guarantee respect for the rules of production, the Regulation provides for an inspection system to ensure that operators who produce, prepare or store organic products or import them from third countries notify the competent private and public authorities in the Member States of their activities. These inspection authorities must, at the very least, ensure application of the minimum inspection and precautionary measures laid down in Annex III to the Regulation. For the production of meat, the Regulation states that the Member States must guarantee the traceability of products throughout the production, processing and preparation chain.

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국내 상호접속료 산정방식의 문제점 분석

  • Yang, Won-Seok;Jeong, Ji-Hyeong
    • Proceedings of the Korea Database Society Conference
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    • 2010.06a
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    • pp.181-185
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    • 2010
  • The current method for accessing interconnection charges in Korea, called a hybrid model in this paper, mixes a top-down with a bottom-up LRIC model. The method has given stable charges so far. However, according to the fundamental changes of the market, policy, and network technology in the telecommunications industry, it requires analyzing the validity of the method. We investigate the problems of the top-clown, bottom-up, and hybrid model used in Korea and analyze their effect on regulation policy.

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Down-regulation of Phosphoglucose Isomerase/Autocrine Motility Factor Enhances Gensenoside Rh2 Pharmacological Action on Leukemia KG1α Cells

  • You, Zhi-Mei;Zhao, Liang;Xia, Jing;Wei, Qiang;Liu, Yu-Min;Liu, Xiao-Yan;Chen, Di-Long;Li, Jing
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.3
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    • pp.1099-1104
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    • 2014
  • Aims and Background: Ginsenoside Rh2, which exerts the potent anticancer action both in vitro and in vivo, is one of the most well characterized ginsenosides extracted from ginseng. Although its effects on cancer are significant, the underlying mechanisms remain unknown. In this study, we sought to elucidate possible links between ginsenoside Rh2 and phosphoglucose isomerase/autocrine motility factor (PGI/AMF). Methods: $KG1{\alpha}$, a leukemia cell line highly expressing PGI/AMF was assessed by western blot analysis and reverse transcription- PCR (RT-PCR) assay after transfection of a small interfering (si)-RNA to silence PGI/AMF. The effect of PGI/AMF on proliferation was measured by typan blue assay and antibody array. A cell counting kit (CCK)-8 and flow cytometry (FCM) were adopted to investigate the effects of Rh2 on PGI/AMF. The relationships between PGI/AMF and Rh2 associated with Akt, mTOR, Raptor, Rag were detected by western blot analysis. Results: KG1${\alpha}$ cells expressed PGI/AMF and its down-regulation significantly inhibited proliferation. The antibody array indicated that the probable mechanism was reduced expression of PARP, State1, SAPK/JNK and Erk1/2, while those of PRAS40 and p38 were up-regulated. Silencing of PGI/AMF enhanced the sensibility of $KG1{\alpha}$ to Rh2 by suppressing the expression of mTOR, Raptor and Akt. Conclusion: These results suggested that ginsenoside Rh2 suppressed the proliferation of $KG1{\alpha}$, the same as down-regulation of PGI/AMF. Down-regulation of PGI/AMF enhanced the pharmacological effects of ginsenoside Rh2 on KG1${\alpha}$ by reducing Akt/mTOR signaling.

Cyanate Induces Apoptosis of Rat Glioma Cell Line (시안산에 의한 신경아교종세포의 자멸사)

  • Choi, Hye-Jung;Lee, Sang-Hee
    • Journal of Life Science
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    • v.27 no.3
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    • pp.267-274
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    • 2017
  • The patient with end-stage renal disease show several nervous complications. The factors contributing to the nervous complications are still incompletely characterized. Cyanate, known as one of the uremic toxins, is derived spontaneously from urea. To investigate the mechanism of cyanate-induced effect on C6 glioma cells, the glioma cells were treated with 0, 1, 5, 10, 20 and 40 mM cyanate. There was a dose-dependent decrease in cell viability and the decreased number of cell was observed in glioma cells by treatment with cyanate. Western blot showed the down- regulation of procaspase-3, which means up-regulation of caspase-3, and the up-regulation of caspase-8, but the down-regulation by cyanate. In addition, cDNA microarray showed 934 down-regulated genes and 165 up-regulated genes on 1,099 genes in cyanate treated group. Treatment with cyanate led to 16 down-regulated genes and 6 up-regulated genes on apoptosis category, and especially heat shock 70 kD protein 1A gene on the category of apoptosis was significantly up-regulated. These results suggest that cyanate can induce apoptosis through caspase-8 and caspase-3 in glioma cells and decrease of gene expression including apoptosis category in glioma cells. These effects of cyanate may play a role in the nervous complications of patient with end-stage renal disease.