• Title/Summary/Keyword: Gene regulation

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The Effect of Dexamethasone on Gene Expression and Total Amount of Surfactant Protein A (스테로이드제가 Surfactant Protein A의 유전자 발현과 총단백량에 미치는 영향에 관한 실험적 연구)

  • Lim, Byung Sung;Sohn, Jang Won;Yang, Seok Chul;Yoon, Ho Joo;Shin, Dong Ho;Park, Sung Soo
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.4
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    • pp.395-404
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    • 2002
  • Background : Surfactant protein A (SP-A) is important for regulating surfactant secretion, synthesis and recycling. However, It's regulation in vivo is unclear. SP-A has important roles in regulating surfactant metabolism as well as determining its physical properties. Glucocorticoid accelerates the morphologic differentiation of epithelial cells into type II cells and increase the rate of phosphatidylcholine synthesis. Methods : The authors investigated the effects of glucocorticoid on the accumulation of mRNA encoding SP-A and SP-A protein content. Adult rats were given various doses of subcutaneous dexamethasone and sacrificed after 24 hours and one week. SP-A mRNA was measured using a filter hybridization method. The lung SP-A protein content was determined using a double sandwich ELISA assay with polyclonal antiserum raised in rabbits against purified rat SP-A. Results : 1) The accumulation of SP-A mRNA in the dexamethasone treated group 24 hours after 0.2 mg/kg dexamethasone treatment was increased 38.8% compared to the control group. 2) The accumulation of SP-A mRNA in the dexamethasone treated group 1 week after 2 mg/kg dexamethasone treatment was 49.7% higher than the control group(P<0.01). 3) The total lung SP-A level was not altered after 24 hours by the 0.2mg/kg treatment. The total lung SP-A content one week after 2mg/kg dexamethasone administration was 373.7% higher than the control group(P<0.005). Conclusion : Dexamethasone treatment results in an increase in the SP-A mRNA and SP-A protein levels, suggesting that the pretranslational events in vivo may in part contribute to this process.

THE EFFECT OF BONE MORPHOGENETIC PROTEIN 2(BMP2) ON THE GROWTH OF CRANIAL BONE AND EARLY MORPHOGENESIS OF THE CRANIAL SUTURE (Bone Morphogenetic Protein 2 가 두개골 성장 및 두개봉합부의 초기형태발생에 미치는 영향)

  • Jung, Hae-Kyung;Park, Mi-Hyun;Ryoo, Hyun-Mo;Nam, Soon-Hyeun;Kim, Young-Jin;Kim, Hyun-Jung
    • Journal of the korean academy of Pediatric Dentistry
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    • v.30 no.2
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    • pp.217-228
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    • 2003
  • Co-ordinate growth of the brain and skull is achieved through a series of tissue interactions between the developing brain, the growing bones of the skull and the sutures that unite the bones. Craniosynostosis, the premature fusion of cranial sutures, presumably involves disturbance of these interactions. Bmp2, one of bone morphogenetic proteins (Bmps), is involved in the regulation of the shapes of individual bones and the relative proportions of the skeleton. Mutations in the homeobox gene Msx2, known as a downstream gene of Bmp, cause Boston-type human craniosynostosis. The phenotype of Dlx5 homozygote mutant mouse presents craniofacial abnormalities including a delayed ossification of calvarial bone. These facts suggest important roles of Bmp2, Msx2 and Dlx5 genes in the cranial bone growth and suture morphogenesis. To elucidate the function of these molecules in the early morphogenesis of mouse cranial sutures, we first analyzed by in situ hybridization the expression of Bmp2(E15-18), Msx2 and Dlx5 genes in the developing sagittal suture of calvaria during the embryonic stage. Bmp2 mRNA was intensely expressed in the osteogenic fronts and also at the low level in the periosteum of parietal bones during embryonic stage, Msx2 mRNA was intensely expressed in the sutural mesenchyme and mildly expressed in the dura mater during the embryonic stage. Dlx5 mRNA was intensely expressed osteogenic fronts and parietal bones. To further examine the role of Bmp signaling in cranial suture, we did in vitro experiments in E15.5 mouse calvarial explants. Interestingly, implantation of Bmp2-soaked beads onto the osteogenic fronts after 48 hours organ culture resulted in the increase of the tissue thickness and cell number around Bmp2 beads, compared to BSA control beads. In addition Bmp2 induced etopic expressions of Msx2 and Dlx5 genes. On the other hand, overexpression of FGF2 did not induce the expression of Msx2 and Dlx5. Taken together, these data indicate that Bmp2 signaling molecule has a important role in regulating the cranial bone growth and early morphogenesis of cranial suture. We also suggest that Bmp signaling is involved in all the stages of osteogenesis of cranial bones and the maintenance of cranial suture by regulating Msx2 and Dlx5 genes, and that Msx2 and Dlx5 genes are specific transcription factors of Bmp signaling pathway.

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Antioxidative Activities of the Codonopsis lanceolata Extract in vitro and in vivo (더덕(Codonopsis lanceolata) 추출물의 in vitro 및 in vivo 항산화 효과)

  • Kim, Soo-Hyun;Chung, Mi-Ja;Jang, Hae-Dong;Ham, Seung-Shi
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.2
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    • pp.193-202
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    • 2010
  • In vitro activities of Codonopsis lanceolata (CL) 70% ethanol extract and its fractions (hexane, chloroform, ethyl acetate, butanol and water) were examined by total polyphenol content, reducing power, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS), 2,2-diphenyl-$\beta$-picrylhydrazyl (DPPH), and oxygen radical absorbance capacity (ORAC) assays. The ethyl acetate fraction from CL ethanol extract (CLEA) showed the highest total polyphenol content (22.7 mg/g) among five fractions, and also exhibited an excellent reducing power (0.42~1.27 at $250\sim1,000\;{\mu}g/mL$). CLEA at $100\sim400\;{\mu}g/mL$ concentrations had 27.7~70.3% of ABTS radical scavenging activity and the highest DPPH radical scavenging activity (81.6% at $400\;{\mu}g/mL$). CLEA had dominantly higher $ORAC_{{ROO}{\cdot}}$activity compared to other fractions. CLEA and butanol fraction had significantly higher $ORAC_{{OH}{\cdot}}$ activities than 70% ethanol extract, hexane, chloroform and water fractions. The CLEA exhibited the highest antioxidant activity in CL 70% ethanol extract and its fractions. Thus, effect of CLEA treatment on antioxidant gene expression under the oxidative stress conditions by a high fat diet in animal model was studied by microarray and RT-PCR methods. The 31 antioxidant genes were expressed but the genes were not up-regulated at least a two-fold by CLEA treatment. We concluded that CLEA does not have an indirect antioxidant effect but a direct antioxidant effect by up-regulation of antioxidant genes in high fat diet-induced obese mice.

Association Study between Porcine LEPR-derived Microsatellite Polymorphisms and Economic Traits (돼지 leptin receptor내 초위성체 다형성과 경제형질과의 연관성 구명)

  • Choi, B.H.;Kim, T.H.;Cho, Y.M.;Lee, H.Y.;Jeon, J.T.;Cheong, I.C.
    • Journal of Animal Science and Technology
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    • v.45 no.5
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    • pp.679-688
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    • 2003
  • The leptin receptor gene(LEPR) produces a high affinity receptor that mediates the regulation of the leptin gene. Leptin secreted from adipose tissue plays an important role in regulating feed intake and energy balance. In this study, a microsatellite marker within LEPR was selected and genotyped for the F2 population composed of 354 individuals from an intercross between Korean Native boars and Landrace sows. Totally, six alleles (255, 259, 261, 263, 265 and 267bp) and nineteen genotypes were detected in the population, of which the CE (261/265), CC (261/261) and EE (265/265) types were observed by 20.0%, 10.1% and 9.6%, respectively. Relationships between their genotypes and economic traits were analyzed. We found specific genotypes associated with economic traits such as body weight at 12 weeks of age/body fat including abdominal and trimmed fat/shear force (P〈0.001), body weight of 30 weeks of age (P〈0.01) and body weight of 3 weeks of age/back fat thickness (P〈0.05). The DD (263/263) and DF (263/267) types were associated with body weight at 3, 5, 12 and 30 weeks of age. The DF (263/267) type showed a highly significant effect on back fat thickness and body fat including abdominal and trimmed fat. The DF (263/267) type showed positive effect on shear force, whereas the BB (259/259) and DD (263/263) types negatively affected on tenderness.

Application of Transposable Elements as Molecular-marker for Cancer Diagnosis (암 진단 분자 마커로서 이동성 유전인자의 응용)

  • Kim, Hyemin;Gim, Jeong-An;Woo, Hyojeong;Hong, Jeonghyeon;Kim, Jinyeop;Kim, Heui-Soo
    • Journal of Life Science
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    • v.27 no.10
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    • pp.1215-1224
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    • 2017
  • Until now, various oncogenic pathways were idenfied. The accumulation of DNA mutation induces genomic instability in the cell, and it makes cancer. The development of bioinformatics and genomics, to find the precise and reliable biomarker is available. This biomarker could be applied the early-dignosis, prediction and convalescence of cancer. Recently, Transposable elements (TEs) have been attracted as the regulator of genes, because they occupy a half of human genome, and the cause of various diseases. TEs induce DNA mutation, as well as the regulation of gene expression, that makes to cancer development. So, we confirmed the relationship between TEs and colon cancer, and provided the clue for colon cancer biomarker. First, we confirmed long interspersed nuclear element-1 (LINE-1), Alu, and long terminal repeats (LTRs) and their relationship to colon cancer. Because these elements have large composition and enormous effect to the human genome. Interestingly, colon cancer specific patterns were detected, such as the hypomethylation of LINE-1, LINE-1 insertion in the APC gene, hypo- or hypermethylation of Alu, and isoform derived from LTR insertion. Moreover, hypomethylation of LINE-1 in proto-oncogene is used as the biomarker of colon cancer metastasis, and MLH1 mutation induced by Alu is detected in familial or hereditary colon cancer. The genes, effected by TEs, were analyzed their expression patterns by in silico analysis. Then, we provided tissue- and gender-specific expression patterns. This information can provide reliable cancer biomarker, and apply to prediction and diagnosis of colon cancer.

Dependency on p53 in Expression Changes of ATF3 and NAG-1 Induced by EGCG, Genistein, and Resveratrol (EGCG, genistein, resveratrol 처리에 의한 ATF3와 NAG-1 유전자 발현변화의 p53 의존성 분석)

  • Kim, Min-Jeong;Kim, Hyun-Ji;Seo, Yu-Mi;Lee, Eun-Joo;Kim, Jong-Sik
    • Journal of Life Science
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    • v.28 no.5
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    • pp.615-620
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    • 2018
  • Epigallocatechin-3-gallate (EGCG), one of catechins of green tea, has been known to possess anti-oxidation, anti-inflammation, and anti-cancer effects. The present study analyzed global gene expression changes in EGCG-treated HCT116 cells and p53-null HCT116 cells by oligo DNA microarray analysis. Among the differentially expressed genes in EGCG-treated HCT116 cells, four were selected that are known as tumor suppressor genes (activating transcription factor 3 [ATF3], cyclin dependent kinase inhibitor 1A [CDKN1A], DNA damage-inducible transcript 3 [DDIT3] and non-steroidal anti-inflammatory drug activated gene [NAG-1]) and their expression was compared to the expression of genes in p53-null HCT116 cells. We found that the expression of these genes was not dependent on their p53 status except for NAG-1, which was only up-regulated in HCT116. The results of RT-PCR and Western blot analysis showed that ATF3 up-regulation by EGCG was not affected by the presence of p53, whereas NAG-1 expression was not induced in p53-null HCT116 cells. We also detected ATF3 and NAG-1 expression changes through genistein and resveratrol treatment. Interestingly, genistein could not up-regulate ATF3 regardless of p53 status, but genistein could induce NAG-1 only in HCT116 cells. Resveratrol could significantly induce NAG-1 as well as ATF3 independent of p53 presence. These results indicate that EGCG, genistein and resveratrol may have different anti-cancer effects. Overall, the results of this study may help to increase our understandings of molecular mechanisms on anti-cancer activities mediated by EGCG, genistein and resveratrol in human colorectal cancer cells.

Effect of Dexamethasone on Gene Expression of Surfactant Protein B and Surfactant Protein C (스테로이드제가 백서 폐의 Surfactant B와 C 유전자 발현에 미치는 영향)

  • Park, Ik Soo;Sohn, Jang Won;Yoon, Ho Joo;Shin, Dong Ho;Park, Sung Soo
    • Tuberculosis and Respiratory Diseases
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    • v.54 no.4
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    • pp.439-448
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    • 2003
  • Background : Surfactant protein B(SP-B) and surfactant protein C(SP-C) are important in accelerating surface spreading of surfactant phospholipid. The glucocorticoids accelerate the morphologic differentiation of epithelial cells into type II cells and increase the rate of phosphatidylcholine synthesis. The hydrophobic surfactant protein has been shown to be upregulated by glucocorticoids in vitro, however, its regulation in vivo is not well established. Methods : The authors investigated the effects of glucocorticoid on the accumulation of mRNA encoding SP-B and SP-C protein content of the lung. Adult rats were given different doses of subcutaneous dexamethasone and sacrificed at 24 hours and 1 week. SP-B and SP-C mRNA were measured by a filter hybridization method. Results : 1) The accumulation of SP-B mRNA at 24 hours after 0.2 mg/kg dexamethasone treatment was increased by 23.7%. 2) The accumulation of SP-B mRNA at 1 week after 2 mg/kg dexamethasone treatment was significantly increased by 96.6%(P<0.001). 3) The accumulation of SP-C mRNA at 24 hours after 0.2 mg/kg dexamethasone treatment was significantly increased by 42.7%(P<0.01). 4) The accumulation of SP-C mRNA at 1 week after 2 mg/kg dexamethasone treatment was significantly increased by 60.0% (P<0.01). Conclusion : The authors concluded that dexamethasone treatment in vivo resulted in increased levels of SP-B mRNA and SP-C mRNA. These results suggested that dexamethasone stimulates the synthesis of hydrophobic proteins associated with surfactant.

THE EFFECT OF FIBROBLAST GROWTH FACTOR SIGNALING ON CARTILAGE FORMATION (FGF signaling이 연골 형성에 미치는 영향)

  • Park, Choong-Je;Lee, Sang-Won;Nam, Soon-Hyun;Kim, Young-Jin;Ryoo, Hyhn-Mo;Kim, Hyun-Jung
    • Journal of the korean academy of Pediatric Dentistry
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    • v.30 no.4
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    • pp.643-653
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    • 2003
  • Fibroblast growth factor (FGF) / FGF receptor (FGFR) mediated signaling is required for skeletogenesis in cluding intramembranous and endochondral ossifications Runx2 ($Cbfa1/Pebp2{\alpha}A/AML3$) is an essential transcription factor for osteoblast differentiation and bone formation. Murine calvaria and mandible are concurrently undergoing both intramembranous bone and cartilage formations in the early developmental stage. However the mechanism by which these cartilage formations are regulated remains unclear. To elucidate the effect of FGF signaling on development of cranial sutural cartilage and Meckel's cartilage and to understand the role of Runx2 in these process, we have done both in vivo and in vitro experiments. Alcian blue staining showed that cartilage formation in sagittal suture begins from embryonic stage 16 (E16), Meckel's cartilage formation in mandible from E12. We analyzed by in situ hybridization the characteristics of cartilage cells that type II collagen, not type X collagen, was expressed in sagittal sutural cartilage and Meckel's cartilage. In addition, Runx2 was not expressed in Meckel's cartilage as well as sagittal sutural cartilage, except specific expression pattern only surrounding both cartilages. FGF signaling pathway was further examined in vitro. Beads soaked in FGF2 placed on the sagittal suture and mandible inhibited both sutural and Meckel's cartilage formations. We next examined whether Runx2 gene lies in FGF siganling pathway during regulation of cartilage formation. Beads soaked in FGF2 on sagittal suture induced Runx2 gene expression. These results suggest that FGF signaling inhibits formations of sagittal sutural and Meckel's cartilages, also propose that FGF siganling is involved in the proliferation and differentiation of chondroblasts through regulating the transcription factor Runx2.

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Antioxidant Effect of Hot water and Ethanol extracts from Cheonnyuncho (Opuntia humifusa) on Reactive Oxygen Species (ROS) Production in 3T3-L1 Adipocytes (3T3-L1 지방세포내 ROS 생성에 대한 천년초 열수 및 에탄올 추출물의 항산화 효과)

  • Yoon, Bo-Ra;Lee, Young-Jun;Kim, Sun-Gu;Jang, Jung-Young;Lee, Hyo-Ku;Rhee, Seong-Kap;Hong, Hee-Do;Choi, Hyeon-Son;Lee, Boo-Yong;Lee, Ok-Hwan
    • Food Science and Preservation
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    • v.19 no.3
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    • pp.443-450
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    • 2012
  • Recently, NADPH oxidase 4 (NOX4)-mediated generation of intracellular reactive oxygen species (ROS) was proposed to accelerate adipogenesis of 3T3-L1 cell. We have previously shown that Cheonnyuncho (Opuntia humifusa) extract significantly inhibited adipocyte differentiation via downregulation of $PPAR{\gamma}$ (peroxisome proliferator-activated receptor gamma) gene expression. In this study, we focused on the molecular mechanism(s) of NOX4, G6PDH (glucose-6-phosphate dehydrogenase) and antioxidant enzymes in anti-oxidative activities of 3T3-L1 adipocytes. Our results indicate that Cheonnyuncho extracts markedly inhibits ROS production during adipogenesis in 3T3-L1 cells. Cheonnyuncho extracts suppressed the mRNA expression of the pro-oxidant enzyme such as NOX4 and the NADPH-producing G6PDH enzyme. In addition, treatment with Cheonnyuncho extract was found to upregulate mRNA levels of antioxidant enzymes such as Mn-SOD (manganese-superoxide dismutase), Cu/Zn-SOD (copper/zinc-SOD), glutathione peroxidase (GPx), glutathion reductase (GR), and catalase, all of which are important for endogenous antioxidant responses. These data suggest that Cheonnyuncho extract may be effective in preventing the rise of oxidative stress during adipocyte differentiation through mechanism(s) that involves direct down regulation of NOX4 and G6PDH gene expression or via upregulation of endogenous antioxidant responses.

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.