• Title/Summary/Keyword: down-regulation

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Inhibitory Actions of Steppogenin on Platelet Activity Through Regulation of Glycoprotein IIb/IIIa and Ca2+ Mobilization (Glycoportein IIb/IIIa와 칼슘동원의 조절을 통한 Steppogenin의 혈소판활성 억제효과)

  • Shin, Jung-Hae;Ha, Ju-Yeon;Kwon, Hyuk-Woo
    • Korean Journal of Pharmacognosy
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    • v.51 no.2
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    • pp.100-106
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    • 2020
  • The extract of Cudrania tricuspidata is used in ethnomedicine throughout Eastern Asia in China, Korea and Japan. In Korean traditional medicine, Cudrania tricuspidata has been used to treat eczema, mumps, tuberculosis, contusions, insomnia and acute arthritis. In addition, it has been reported that root extract of Cudrania tricuspidata has anti-platelet effects. Therefore, we investigated which compound in Cudrania tricuspidata has inhibitory effect on platelet aggregation. In this study, we tried to explain the inhibitory mechanism of steppogenin from Cudrania tricuspidata on human platelet aggregation. Collagen-induced human platelet aggregation and [Ca2+]i mobilization were dose-dependently inhibited by steppogenin and we determined the inhibition by steppogenin is due to the down regulation of extracellular-signal-regulated kinase(ERK) and inositol-1,4,5-triphosphate receptor type I(IP3RI) phosphorylation. In addition, steppogenin inhibited collagen-induced fibronectin adhesion to αIIb/β3 and thromboxane A2 generation. Thus, in the present study, steppogenin showed an inhibitory effect on human platelet aggregation, suggesting its potential use for preventing platelet-induced cardiovascular disease.

Involvement of hydrogen peroxide in the regulation of IAA level in plants (IAA수준의 조절에 미치는 과산화수소의 영향)

  • Park, Ro-Dong;Kim, Jeong-Bong;Park, Chang-Kyu
    • Applied Biological Chemistry
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    • v.33 no.2
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    • pp.129-132
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    • 1990
  • The role of hydrogen peroxide which is accumulated in plants under low temperature has been studied with respect to the regulation of physiological IAA level. At 10 mM of $H_2O_2$, accelerating effects of IAA on the elongation of Avena coleoptiles and the root Initiation of pea cuttings have been greatly inhibited. These inhibitions were reversed by introduction of catalase. The reaction of free IAA with Salkowski reagent was inhibited in the presence of $H_2O_2$, but that of IAA-glutamic acid was not, suggesting the inactivation of free IAA by $H_2O_2$. The data support that increase in the content of hydrogen peroxide under low temperature partially down-regulates the available IAA through inactivation of IAA.

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Cardiac hypertrophy and abnormal $Ca^{2+}$ handling in transgenic mice overexpressing jnnctate

  • Hong, Chang-Soo;Cho, Myeong-Chan;Kwak, Yong-Geun;Chane, Soo-Wan;Kim, Do-Han
    • Proceedings of the Korean Biophysical Society Conference
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    • 2003.06a
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    • pp.52-52
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    • 2003
  • Junctate is a newly identified integral ER/SR membrane $Ca^{2+}$ binding protein, which is an alternative splicing form of the same gene generating aspartyl $\square$-hydroxylase and junctin. To elucidate the functional role of junctate in heart, transgenic (TG) mice overexpressing mouse cardiac junctate-1 under the control of mouse $\square$$^{~}$ myosin heavy chain promoter were generated. Overexpression of junctate in mouse heart resulted in cardiac hypertrophy, increased fibrosis, bradycardia, arrhythmias and impaired contractility. Overexpression of junctate also led to down-regulation of SERCA2, calsequestrin, calreticulin and RyR, but to up-regulation of NCX and PMCA. The SR $Ca^{2+}$ content decreased and the L-type $Ca^{2+}$ current density and the action potential durations increased in TG cardiomyocytes, which could be the cause for the bradycardia in TG heart. The present work has provided an important example of pathogenesis leading to cardiac hypertrophy and arrhythmia, which was caused by impaired $Ca^{2+}$ handling by overexpression of junctate in heart.n heart.

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Production of Liquiritigenin with Cell-based Biotransformation and Its Anti-Aging Activity (균사체 생물전환기술을 이용한 리퀘리티게닌 생산과 항노화 활성)

  • Hwang, Hye Jin;Jeong, Sang Chul;Park, Jong Pil
    • KSBB Journal
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    • v.30 no.4
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    • pp.166-174
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    • 2015
  • In this study, an efficient whole cell-based biotransformation for the production of liquiritigenin was developed using Laetiporus sulphureus CS0218 as biocatalyst and aqueous extracts of Glycyrrhiza uralensis as co-substrate, respectively. In order to determine the efficacy of this method, the optimal bioconversion conditions including mycelial growth, three important enzyme activities (${\beta}$-glucosidase, ${\alpha}$-rhamnosidase and ${\beta}$-xylosidase), and apparent viscosity of culture broth were monitored. After optimization, aqueous extracts of G. uralensis were added to the culture medium to directly produce algycone liquiritigenin. By applying this strategy, 67.5% of liquiritin was converted to liquiritigenin at pH 3.0 after 9 days of incubation and finally liquiritigenin was purified from the reaction mixture. And then, their biological activities including anti-oxidant and superoxide dismutase were observed. In fact, purified liquiritigenin was capable of bi-directional functions (i.e., either up-regulation or down-regulation of SIRT1 which is associated with aging). The results indicate that this strategy would be beneficial to produce biologically active liquiritigenin and could be used in pharmaceutical, cosmetic and food applications.

Aging and UV Irradiation Related Changes of Gene Expression in Primary Human Keratinocytes

  • Lee, Ok Joo;Lee, Sung-Young;Park, Jae-Bong;Lee, Jae-Yang;Kim, Jong-Il;Kim, Jaebong
    • Genomics & Informatics
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    • v.3 no.2
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    • pp.66-72
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    • 2005
  • The epidermis is a physiological barrier to protect organisms against environment. During the aging process, skin tissues undergo various changes including morphological and functional changes. The transcriptional regulation of genes is part of cellular reaction of aging process. In order to examine the changes of gene expression during the aging process, we used the primary cell culture system of human keratinocytes. Since UV radiation is the most important environmental skin aggressor, causing skin cancer and other problems including premature skin aging, we examined the changes of gene expression in human keratinocytes after UV irradiation using oligonucleotide microarray containing over 10,000 genes. We also compared the gene expression patterns of the senescent and UV treated cells. Expression of the variety of genes related to transcription factors, cell cycle regulation, immune response was altered in human keratinocytes. Some of down-regulated genes are represented in both senescent and UV treated cells. The results may provide a new view of gene expression following UVB exposure and aging process in human keratinocytes.

Immunofluorescence Microscopic Evaluation of Tight Junctional Proteins during Enterotoxigenic Bacteroides fragilis (ETBF) Infection in Mice

  • Hwang, Soonjae;Kang, Yeowool;Jo, Minjeong;Kim, Sung Hoon;Cho, Won Gil;Rhee, Ki-Jong
    • Biomedical Science Letters
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    • v.24 no.3
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    • pp.275-279
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    • 2018
  • Inflammatory bowel disease (IBD) is increasing in prevalence in developed countries but the cause of this increase is unclear. In animal models of IBD and in human IBD patients, alterations in the tight junctional proteins have been observed, suggesting that the intestinal microflora may penetrate the underlying colonic tissue and promote inflammation. Enterotoxigenic Bacteroides fragilis (ETBF) causes inflammatory diarrhea in human and is implicated in inflammatory bowel diseases. However, it is unclear whether alterations in tight junctional proteins occur during ETBF infection in mice. In this brief communication, we report that ETBF infection induces up-regulation of claudin-2 and down-regulation of claudin-5 through B. fragilis toxin (BFT) activity in the large intestine of C57BL/6 mice. In contrast, BFT did not induce changes in tight junctional proteins in the HT29/C1 cell line, suggesting that analysis of biological activity of BFT in vivo is important for evaluating ETBF effects.

Human selenium binding protein-1 (hSP56) is a negative regulator of HIF-1α and suppresses the malignant characteristics of prostate cancer cells

  • Jeong, Jee-Yeong;Zhou, Jin-Rong;Gao, Chong;Feldman, Laurie;Sytkowski, Arthur J.
    • BMB Reports
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    • v.47 no.7
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    • pp.411-416
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    • 2014
  • In the present study, we demonstrate that ectopic expression of 56-kDa human selenium binding protein-1 (hSP56) in PC-3 cells that do not normally express hSP56 results in a marked inhibition of cell growth in vitro and in vivo. Down-regulation of hSP56 in LNCaP cells that normally express hSP56 results in enhanced anchorage-independent growth. PC-3 cells expressing hSP56 exhibit a significant reduction of hypoxia inducible protein (HIF)-$1{\alpha}$ protein levels under hypoxic conditions without altering HIF-$1{\alpha}$ mRNA (HIF1A) levels. Taken together, our findings strongly suggest that hSP56 plays a critical role in prostate cells by mechanisms including negative regulation of HIF-$1{\alpha}$, thus identifying hSP56 as a candidate anti-oncogene product.

Expression of the Heat Shock Proteins in HeLa and Fish CHSE-214 Cells Exposed to Heat Shock (어류 CHSE-214와 인간 HeLa 세포에서의 열충격에 의한 Heat Shock Protein의 발현)

  • 공회정;강호성김한도
    • The Korean Journal of Zoology
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    • v.39 no.2
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    • pp.123-131
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    • 1996
  • In this study, we examined the expression of heat shock proteins (HSPs) in fish cell line CHSE-2lnl and human HeLa cells exposed to heat shock. In fish CHSE-214 cells HSP70 was the major polvpeptide induced by an elevated temperature or an amino acid analog, while in HeLa cells HSP90 as well as HSP70 were prominently enhanced in response to these stresses. Pretreatment of actinomvcin D prior to heat shock completely inhibited the induction of fish HSP70, indicating the transcriptional regulation of fish HSP70 gene expression. In HeLa and CHSE-214 cells either recovering from heat shock or experiencing prolonged heat shock, attenuation in the HSP90 a'nd HSP70 induction occurred but both induction and repression of HSP70 synthesis appear 19 precede those of HSP90. Moreover, attenuation did not occur in the syntheses of 40 kDa and 42 kOto proteins which were only induced in CHSE-214 cells. The enhanced syntheses of these he proteins continued as long as CHSE-214 cells were Siven heat shock. These results suggest that down-regulation of HSP syntheses during prolonged heat shock may be controlled by several different. as vet undefined, mechanisms.

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Effect of Apoptosis Induction of Ailanthus altissima on Human Lung Carcinoma Cells

  • Hwang, Yu-Jin;Woo, Hye-Im;Kim, Inhye;Park, Dong-Sik;Kim, Jaehyun;Om, Ae-Son;Hwang, Kyung-A
    • Journal of agriculture & life science
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    • v.45 no.5
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    • pp.91-96
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    • 2011
  • We investigated the inhibitory effects of solvent extracts from Ailanthus altissima in A549 human lung cancer cell. A. altissima has been recognized as a traditional healthy food due to its various biological activities against hypertension, strokes, fever, pain, neuralgia, inflammation, and cancer effects. Recently, it has been reported that the extracts of various wild vegetables show strong anti-cancer properties by induction of apoptosis. However, the mechanisms of their cytotoxicity in human lung cancer cells have been poorly understood. The present study was investigated the effects of solvent extracts from A. altissima on cell growth and apoptosis on A549 human lung cancer cells. A treatment of A. altissima inhibited the growth of A549 cells in a dose-dependent manner by inducing apoptosis. Especially, the chloroform fraction showed the highest anti-cancer effect among five kinds of fractions. And also, induction of apoptosis by chloroform fraction were associated with down-regulation of Bcl-2, and up-regulation of pro-apoptotic Bax expression. From these results, A. altissima may have a therapeutic potential in human lung cancer cells and as a functional food.

SETDB1 regulates SMAD7 expression for breast cancer metastasis

  • Ryu, Tae Young;Kim, Kwangho;Kim, Seon-Kyu;Oh, Jung-Hwa;Min, Jeong-Ki;Jung, Cho-Rok;Son, Mi-Young;Kim, Dae-Soo;Cho, Hyun-Soo
    • BMB Reports
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    • v.52 no.2
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    • pp.139-144
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    • 2019
  • Breast cancer (BRC) is the most invasive cancer in women. Although the survival rate of BRC is gradually increasing due to improved screening systems, development of novel therapeutic targets for inhibition of BRC proliferation, metastasis and recurrence have been constantly needed. Thus, in this study, we identified overexpression of SETDB1 (SET Domain Bifurcated 1), a histone methyltransferase, in RNA-seq data of BRC derived from TCGA portal. In Gene Ontology (GO) analysis, cell migration-related GO terms were enriched, and we confirmed down-regulation of cell migration/invasion and alteration of EMT /MET markers after knockdown of SETDB1. Moreover, gene network analysis showed that SMAD7 expression is regulated by SETDB1 levels, indicating that up-regulation of SMAD7 by SETDB1 knockdown inhibited BRC metastasis. Therefore, development of SETDB1 inhibitors and functional studies may help develop more effective clinical guidelines for BRC treatment.