• Title/Summary/Keyword: Regulation

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Comparison and Analysis between Human Breast Cancer Cells and Hepatoma Cells for the Effects of Xenobiotic Nuclear Receptors (Constitutive Androstane Receptor, Steroid and Xenobiotic Receptor, and Peroxisome-Proliferator-Activated Receptor γ ) on the Transcriptional Activity of Estrogen Receptor (유방암 세포와 간암세포에 있어서 에스트로겐 수용체의 전사조절기능에 대한 Xenobiotic 핵 수용체 (Constitutive Androstane Receptor, Steroid and Xenobiotic Receptor, Peroxisome-Proliferator-Activated Receptor γ )의 영향 비교분석)

  • 민계식
    • Journal of Life Science
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    • v.13 no.3
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    • pp.314-323
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    • 2003
  • The purpose of this study was to examine the effects of xenobiotic nuclear receptors, CAR, SXR, and PPAR${\gamma}$ on the transcriptional activity of estrogen receptor in human breast cancer cell lines and compare with those in human hepatoma cell line. Two different breast cancer cell lines, MCF-7 and MDA-MB-231 were cultured and effects of CAR, SXR, and PPAR${\gamma}$ on the ER-mediated transcriptional activation of synthetic (4ERE)-tk-luciferase reporter gene were analyzed. Consistent with the previous report, CAR significantly inhibited ER-mediated transactivation and SXR repressed modestly whereas the PPAR${\gamma}$ did not repress the ER-mediated transactivation. However, in breast cancer cells neither of the xenobiotic receptors repressed the ER-mediated transactivation. Instead, they tend to increase the transactivation depending on the cell type and xenobiotic nuclear receptors. In MCF-7, SXR but neither CAR nor PPAR${\gamma}$ slightly increased ER-mediated transactivation whereas in MDA-MB-231, CAR and PPAR${\gamma}$ but not SXR tend to increase the transactivation of the reporter gene. These results indicate that the effects of ER cross-talk by the CAR, SXR, and PPAR${\gamma}$ , are different in breast cancer cells from hepatoma cells. In conclusion, the transcriptional regulation by estrogen can involve different cross-talk interaction between estrogen receptor and xenobiotic nuclear receptors depending on the estrogen target cells.

Study on the Mineral Contents of Commercial powdered infant formula (유아용 조제분유의 무기물 함량에 관한 연구)

  • Kim, Min-Jung;Park, Eun-Kyung;Jun, Mi-Ra;Kim, Young-Gil
    • Journal of Life Science
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    • v.17 no.6 s.86
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    • pp.836-840
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    • 2007
  • This study was conducted to investigate mineral contents of commercial powdered infant formula for obtaining basic data on infant nutrition. 11 Commercial infant formula based on cow's milk were collected and the contents of macro minerals (calcium, phosphorous, sodium, potassium and magnesium) and trace minerals (iron, zinc and copper) were compared with Dietary Reference Intakes for Koreans (KDRIs). The overall mineral contents in 100 g and in 100 kcal of infant formula satisfied the recommended formula regulation and Codex. In infant formula during 0-5 monthly age, calcium, phosphorous, sodium, potassium, magnesium, zinc and copper could supply 233.1%, 273.5%, 156.7%, 142.0%, 150.8%, 209.3%, 171.1% of recommended daily mineral intakes, respectively. The content of iron in 0-5 monthly age formula supplied2842.6% of recommended daily iron intakes. In infant formula during 6-11 monthly age, calcium, phosphorous, potassium, magnesium, iron, zinc and copper satisfied their recommended daily intakes. However, sodium only supplied 76.6% of its recommended daily intake. Intake ratio between Ca/P, Ca/Mg, Ca/Fe, Na/K and Zn/cu in infant formula during 0-5 monthly age were 1.7±0.2, 11.0±2.4,64.9±10.0, 0.3±0.1, and 9.6±1.0, respectively. Intake ratio between Ca/P, Ca/Mg, Ca/Fe, Na/K and Zn/cu in infant formula during 6-11 monthly age were 1.7${\pm}$0.2, 12.9${\pm}$1.5, 80.1${\pm}$13.8, 0.3, and 9.4${\pm}$1.1,respectively. From this study, evaluation of mineral contents of commercial infant formula was established, which could strengthen the basic information on infant nutrition.

Apoptotic Effects and Cell Cycle Arrest Effects of Extracts from Cnidium monnieri (L.) Cusson through Regulating Akt/mTOR/GSK-3β Signaling Pathways in HCT116 Colon Cancer Cells (HCT116 대장암세포에서 AKT/mTOR/GSK-3β 신호경로 조절을 통한 벌 사상자 추출물(CME)의 apoptosis 및 cell cycle arrest 효과)

  • Lim, Eun Gyeong;Kim, Guen Tae;Kim, Bo Min;Kim, Eun Ji;Ha, Sung Ho;Kim, Sang-Yong;Kim, Young Min
    • Journal of Life Science
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    • v.26 no.6
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    • pp.663-672
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    • 2016
  • The Cnidium monnieri (L.) Cusson is an annual plant distributed in China and Korea. The fruit of C. monnieri is used as a medicinal herb that is effective for the treatment of carbuncle and pain in female genitalia. However, the anti-cancer effects of CME have not yet been reported. In this study, we assessed the apoptotic effects and cell cycle arrest effects of ethanol extracts from C. monnieri on HCT116 colon cancer cells. The results of an MTT assay and LDH assay demonstrated a decrease in cell viability and the cytotoxic effects of CME. In addition, the number of apoptotic body and the apoptotic rate were increased in a dose-dependent manner through Hoechst 33342 staining and Annexin V-PI double staining. In addition, cell cycle arrest occurred at the G1 phase by CME. Protein kinase B (Akt) plays an important role in cancer cell survival, growth, and division. Akt down-regulates apoptosis-mediated proteins, such as mammalian target of rapamycin (mTOR), p53, and Glycogen Synthase kinase-3β (GSK-3β). CME could regulate the expression levels of p-Akt, p-mTOR, p-GSK-3β, Bcl-2 family members, caspase-3, and PARP. Furthermore, treatment with CME, LY294002 (PI3K/Akt inhibitor), BIO (GSK-3β inhibitor), and Rapamycin (mTOR inhibitor) showed that apoptotic effects occurred through the regulation of the AKT/mTOR/GSK-3β signaling pathway. Our results demonstrated CME could induce apoptosis and cell cycle arrest in HCT116 colon cancer cells.

Apoptotic Cell Death by Pectenotoxin-2 in p53-Deficient Human Hepatocellular Carcinoma Cells (종양억제유전자 p53 결손 인체간암세포에서 Pectenotoxin-2에 의한 Apoptosis 유도)

  • Shin, Dong-Yeok;Kim, Gi-Young;Choi, Byung-Tae;Kang, Ho-Sung;Jung, Jee-H.;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.17 no.10
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    • pp.1447-1451
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    • 2007
  • Through the screening of marine natural compounds that inhibit cancer cell proliferation, we previously reported that pectenotoxin-2 (PTX-2) isolated from marine sponges exhibits selective cytotoxicity against several cell lines in p53-deficient tumor cells compared to those with functional p53. However, the molecular mechanisms of its anti-proliferative action on malignant cell growth are not completely known. To further explore the mechanisms of its anti-cancer activity and to test whether the status of p53 in liver cancer cells correlates with their chemo-sensitivities to PTX-2, we used two well-known hepatocarcinoma cell lines, p53-deficient Hep3B and p53-wild type HepG2. We have demonstrated that PTX-2 markedly inhibits Hep3B cell growth and induces apoptosis whereas HepG2 cells are much more resistant to PTX-2 suggesting that PTX-2 seems to act by p53-independent cytotoxic mechanism. The apoptosis induced by PTX-2 in Hep3B cells was associated with the modulation of DNA fragmentation factor (DFF) family proteins, up-regulation of pro-apoptotic Bcl-2 family members such as Bax and Bcl-xS and activation of caspases (caspase-3, -8 and -9). Blockade of the caspase-3 activity by caspase-3 inhibitor, z-DEVD-fmk, prevented the PTX-2-induced growth inhibition in Hep3B cells. Moreover, treatment with PTX-2 also induced phosphorylation of AKT and extracellular-signal regulating kinase (ERK), but not c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MARK). Specific inhibitors of PI3K inhibitor (LY294002) and ERK1/2 inhibitor (PD98059) significantly blocks PTX-2-induced-anti-proliferative effects, whereas a JNK inhibitor (SP600125) and a p38 MAPK inhibitor (SB203580) have no significant effects demonstrating that the pro-apoptotic effect of PTX-2 mediated through activation of AKT and ERK signal pathway in Hep3B cells.

Potential Roles of Hedgehog and Estrogen in Regulating the Progression of Fatty Liver Disease (지방간 진행 조절에 대한 헤지호그와 에스트로겐의 잠재적 역할)

  • Hyun, Jeong-Eun;Jung, Young-Mi
    • Journal of Life Science
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    • v.21 no.12
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    • pp.1795-1803
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    • 2011
  • Non-alcoholic fatty liver disease accompanies the rise in the prevalence of obesity, diabetes and the tendency toward high-fat dietary habits. Specifically, the higher prevalence of non-alcoholic fatty liver disease in men and postmenopausal women seems to be caused by the protective effects of estrogen against liver fibrosis, or lack thereof. There are no effective preventive therapies for liver diseases because the mechanisms underlying the progression of fatty liver diseases to chronic liver diseases and the protective effects of estrogen against fibrogenesis remain unclear. Recently, it has been reported that the hedgehog signaling pathway plays an important role in the progression of chronic liver diseases. Hedgehog, a morphogen regulating embryonic liver development, is expressed in injured livers but not in adult healthy livers. The level of hedgehog expression parallels the stages of liver diseases. Hedgehog induces myofibroblast activation and hepatic progenitor cell proliferation and leads to excessive liver fibrosis, whereas estrogen inhibits the activation of hepatic stellate cells to myofibroblasts and prevents liver fibrosis. Although the mechanism underlying the opposing actions of hedgehog and estrogen on liver fibrosis remain unclear, the suppressive effects of estrogen on the expression of osteopontin, a profibrogenic extracellular matrix protein and cytokine, and the inductive effects of hedgehog on osteopontin transcription suggest that estrogen and hedgehog are associated with liver fibrosis regulation. Therefore, further research on the estrogen-mediated regulatory mechanisms underlying the hedgehog-signaling pathway can identify the mechanism underlying liver fibrogenesis and contribute to developing therapies for preventing the progression of fibrosis to chronic liver diseases.

Reactive Oxygen Species Mediates Lysophosphatidic Acid-induced Migration of SKOV-3 Ovarian Cancer Cells (SKOV-3 난소암 세포주에서 lysophosphatidic acid 유도 세포의 이동에 있어 활성산소의 역할)

  • Kim, Eun Kyoung;Lee, Hye Sun;Ha, Hong Koo;Yun, Sung Ji;Ha, Jung Min;Kim, Young Whan;Jin, In Hye;Shin, Hwa Kyoung;Bae, Sun Sik
    • Journal of Life Science
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    • v.22 no.12
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    • pp.1621-1627
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    • 2012
  • Cell motility plays an essential role in many physiological responses, such as development, immune reaction, and angiogenesis. In the present study, we showed that lysophosphatidic acid (LPA) modulates cancer cell migration by regulation of generation of reactive oxygen species (ROS). Stimulation of SKOV-3 ovarian cancer cells with LPA strongly promoted migration. but this migration was completely blocked by pharmacological inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Inhibition of the ERK pathway had no effect on migration. Stimulation of SKOV-3 ovarian cancer cells with LPA significantly induced the generation of ROS in a time-dependent manner. LPA-induced generation of ROS was significantly blocked by pharmacological inhibition of PI3K or Akt, but inhibition of the ERK signaling pathway had little effect. LPA-induced generation of ROS was blocked by pretreatment of SKOV-3 ovarian cancer cells with an NADPH oxidase inhibitor, whereas inhibition of xanthine oxidase, cyclooxygenase, or mitochondrial respiratory chain complex I had no effect. Scavenging of ROS by N-acetylcysteine completely blocked LPA-induced migration of SKOV-3 ovarian cancer cells. Inhibition of NADPH oxidase blocked LPA-induced migration whereas inhibition of xanthine oxidase, cyclooxygenase, or mitochondrial respiratory chain complex I did not affect LPA-induced migration of SKOV-3 ovarian cancer cells. Given these results, we suggest that LPA induces ROS generation through the PI3K/Akt/NADPH oxidase signaling axis, thereby regulating cancer cell migration.

Extract of Rubus coreanus Fruits Increases Expression and Activity of Endothelial Nitric Oxide Synthase in the Human Umbilical Vein Endothelial Cells (복분자 추출물에 의한 내피세포 NO 합성효소의 활성과 발현 증가)

  • Yoon, Hyun-Joong;Park, Soo-Young;Oh, Sung-Tack;Lee, Kee-Young;Yang, Sung-Yeul
    • Journal of Life Science
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    • v.21 no.1
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    • pp.44-55
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    • 2011
  • This study aimed to investigate the effects of water extract of Rubus coreanus (RCE) on the expression and activity of endothelial nitric oxide synthase (eNOS), as well as its signal transduction pathways in human umbilical vein endothelial cells (HUVECs). The specific inhibitors of NOS show RCE treatment increases NO production in HUVECs due to the up-regulation of eNOS rather than iNOS. The real-time expression level of eNOS mRNA was also increased upon RCE treatment in HUVECs. While a PKC-specific inhibitor, RO-317549, did not alter RCE-induced NO production in HUVECs, tamoxifen (estrogen receptor-specific inhibitor), PD98059 (ERK-specific inhibitor) and LY-294002 (PI3K/Akt-specific inhibitor) did have suppressive effects. Increased NO production by RCE seems to result from a higher level of active eNOS (pSer1177). Specifically, inhibition of ERK not only decreased the level of active eNOS, but also increased the inactive form of the enzyme (pThr495) in HUVECs. This study suggests that RCE treatment increases NO production in HUVECs due to the increased expression and activity of eNOS. It is also shown that RCE-induced eNOS activation occurs partly through the binding of RCE to the estrogen receptor, along with ERK and PI3K/Akt-dependent signal transduction pathways. In addition, the regulatory binding proteins of eNOS including Hsp90 and caveolin-1 were related to these effects of RCE on eNOS activity in HUVECs.

Expression of Anion Exchanger and CFTR in the Hepatocyte and Cholangiocytes in Bile Duct-Ligated Rat (담관 결찰 쥐의 간세포와 담관세포의 anion exchanger와 CFTR 발현)

  • Lee, Jae-Dong;Wang, Joon-Ho;Ki, Seung-Seog;Choe, Won-Hyeok;Park, Jae-Seung;Cho, Won-Kyoo;Park, Jung-Jun;Kim, Hong-Su
    • Journal of Life Science
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    • v.21 no.12
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    • pp.1772-1777
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    • 2011
  • Cystic fibrosis transmembrane conductance regulator (CFTR) gene and sodium-independent $Cl^-/HCO_3^-$ anion exchanger (AE) genes are expressed in a wide variety of mammalian tissues including cholangiocytes. They play an important role in the regulation of intracellular pH (pHi) as well as in transepithelial acid/base transport necessary for biliary bicarbonate secretion. The aim of this study was to examine the expression level of CFTR gene and AE genes (AE1, AE2 and AE3) in the cholangiocytes and the hepatocytes, and also measure AE2 gene expression level after bile duct ligation (BDL). As we previously described, isolated hepatocytes and cholangiocytes from the liver of normal and BDL rats were prepared and gene expression levels were measured by using RT-PCR. We found that AE1, AE2, and AE3 genes were expressed in both hepatocytes and cholangiocytes, but CFTR was only in cholangiocytes. AE2 gene expression level was higher in the BDL hepatocytes than normal hepatocytes, which was significantly different between two groups. AE2 gene expression level was lower in the BDL cholangiocytes than normal cholangiocytes. However, AE2 gene expression level in both hepatocytes and cholangiocytes were not changed with a longer duration of BDL. These results suggest that CFTR and AE2 may play an important role in the pathogenetic mechanism of biliary cholestatic liver disease.

Analysis of Putative Downstream Genes of Arabidopsis AtERF71/HRE2 Transcription Factor using a Microarray (마이크로어레이를 이용한 애기장대 AtERF71/HRE2 전사인자의 하위 유전자 분석)

  • Seok, Hye-Yeon;Lee, Sun-Young;Woo, Dong-Hyuk;Park, Hee-Yeon;Moon, Yong-Hwan
    • Journal of Life Science
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    • v.22 no.10
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    • pp.1359-1370
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    • 2012
  • Arabidopsis AtERF71/HRE2, a transcription activator, is located in the nucleus and is involved in the signal transduction of low oxygen and osmotic stresses. In this study, microarray analysis using AtERF71/HRE2-overexpressing transgenic plants was performed to identify genes downstream of AtERF71/HRE2. A total of 161 different genes as well as AtERF71/HRE2 showed more than a twofold higher expression in AtERF71/HRE2-overexpressing transgenic plants compared with wild-type plants. Among the 161 genes, 24 genes were transcriptional regulators, such as transcription factors and DNA-binding proteins, based on gene ontology annotations, suggesting that AtERF71/HRE2 is an upstream transcription factor that regulates the activities of various downstream genes via these transcription regulators. RT-PCR analysis of 15 genes selected out of the 161 genes showed higher expression in AtERF71/HRE2-overexpressing transgenic plants, validating the microarray data. On the basis of Genevestigator database analysis, 51 genes among the 161 genes were highly expressed under low oxygen and/or osmotic stresses. RT-PCR analysis showed that the expression levels of three genes among the selected 15 genes increased under low oxygen stress and another three genes increased under high salt stress, suggesting that these genes might be downstream genes of AtERF71/HRE2 in low oxygen or high salt stress signal transduction. Microarray analysis results indicated that AtERF71/HRE2 might also be involved in the responses to other abiotic stresses and also in the regulation of plant developmental processes.

The moderating effects of ego-resilience on the effects of parents' child-rearing attitude perceived by adolescents and school life adaptation on problem behavior (청소년이 지각한 부모의 양육태도와 학교생활적응이 문제행동에 미치는 영향에서 자아탄력성의 조절효과)

  • Kim, Ji Hye;Yu, Nan Sook
    • Journal of Korean Home Economics Education Association
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    • v.31 no.1
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    • pp.1-19
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    • 2019
  • The purposes of this study were to concretely reveal the effect of the parents' child-rearing attitude perceived by adolescents and the school life adaptation on the problem behavior, and to verify the moderating effect of the ego-resilience on the relationship between the parents' child-rearing attitude and the school life adaptation and the adolescent problem behavior. This study analyzed a total of 2,107 students in the first year of high school, which was the 4th year data(2013) of Korea Children Youth Panel Survey(KCYPS) 2010. The reliability, descriptive statistics, t-test, and hierarchical regression analysis were conducted using SPSS WIN 22.0. The results were as follows. First, the effect of the parents' child-rearing attitude(supervision, affection, reasonable explanation, excessive interference, excessive expectation, and inconsistency), school life adaptation(relationship with teacher, relationship with friend, school regulation, and learning activity), and ego-resilience on the adolescent problem behavior was analyzed. As a result, the relationship with friend(-) had the highest influence on the adolescent problem behavior, followed by learning activity(-), inconsistency(+), ego-resilience(-), excessive interference(+), and supervision(-). However, the remaining sub-variables did not have any significant influence on the adolescent problem behavior. Second, the moderating effect of the ego-resilience on the relationship among the parents' child-rearing attitude, adaptation to school life, and adolescent problem behavior. The ego-resilience was found to moderate the effects of parents' positive child-rearing attitude, interpersonal relationships, and school adaptation on the adolescent problem behavior. However, the moderating effect was not significant for the effect of negative child-rearing attitude on the adolescent problem behavior. Therefore, various ego-resilience enhancement programs need to be developed and researched as a part of the safety education through the home economics class.