• Title/Summary/Keyword: the transcription factors

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APEX-1 Regulates Cell Proliferation through GDNF/GFRα1 Signaling (APEX-1은 GDNF/GFRα1 시그널을 통해 세포증식을 조절한다)

  • Kim, Hong-Beum;Hariharasudhan, Gurusamy;Youn, Cha-Kyung
    • Journal of Life Science
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    • v.23 no.10
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    • pp.1183-1191
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    • 2013
  • Human apurinic/apyrimidinic endonuclease (APEX-1) is a multifunctional protein that is capable of repairing abasic sites and single-strand breaks in damaged DNA. In addition, it serves as a redox-modifying factor for a number of transcription factors. Identifying the transcriptional targets of APEX-1 is essential for understanding how it affects various cellular outcomes. Expression array analysis was used to identify glial cell-derived neurotropic factor receptor ${\alpha}1$ ($GFR{\alpha}1$), which is an encoding receptor for the glial cell-derived neurotropic factor (GDNF) family, the expression of which is induced by APEX-1. A target of GDNF/$GFR{\alpha}$ signaling, c-Src (Tyr418) was strongly phosphorylated by GNDF in the APEX-1 expressing cells. Moreover, GDNF initiated cell proliferation, measured by counting the number of cells, in the APEX-1 expressing cells. Importantly, the down-regulation of APEX-1 by siRNA caused a marked reduction in the $GFR{\alpha}1$ expression level, and it reduced the ability of GDNF to phosphorylate c-Src (Tyr418) and stimulate cell proliferation. These results demonstrate an association between APEX-1 and GDNF/$GFR{\alpha}$ signaling and suggest a potential molecular mechanism for the involvement of APEX-1 in cell survival and proliferation.

G1 Arrest of U937 Human Monocytic Leukemia Cells by Sodium Butyrate, an HDAC Inhibitor, Via Induction of Cdk Inhibitors and Down-regulation of pRB Phosphorylation (Cdk inhibitors의 발현 증가 및 pRB 인산화 저해에 의한 HDAC inhibitor인 sodium butyrate에 의한 인체백혈병세포의 G1 arrest유발)

  • Choi, Yung-Hyun
    • Journal of Life Science
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    • v.19 no.7
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    • pp.871-877
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    • 2009
  • We investigated the effects of sodium butyrate, a histone deacetylase inhibitor, on the cell cycle progression in human monocytic leukemia U937 cells. Exposure of U937 cells to sodium butyrate resulted in growth inhibition, G1 arrest of the cell cycle and induction of apoptosis in a dose-dependent manner as measured by MTT assay and flow cytometry analysis. The increase in G1 arrest was associated with the down-regulation in cyclin D1, E, A, cyclin-dependent kinase (Cdk) 4 and 6 expression, and up-regulation of Cdk inhibitors such as p21 and p27. Sodium butyrate treatment also inhibited the phosphorylation of retinoblastoma protein (pRB) and p130, however, the levels of transcription factors E2F-1 and E2F-4 were not markedly modulated. Furthermore, the down-regulation of phosphorylation of pRB and p130 by this compound was associated with enhanced binding of pRB and E2F-1, as well as p130 and E2F-4, respectively. Overall, the present results demonstrate a combined mechanism involving the inhibition of pRBjp130 phosphorylation and induction of Cdk inhibitors as targets for sodium butyrate that may explain some of its anti-cancer effects in U937 cells.

Melittin inhibits cell migration and invasion via blocking of the epithelial-mesenchymal transition (EMT) in lung cancer cells (EMT 억제를 통한 멜리틴의 폐암세포 이동 및 침투 억제 효과)

  • Cho, Hyun-Ji;Jeong, Yun-Jeong;Kim, Mun-Hyeon;Chung, Il-Kyung;Kang, Dong Wook;Chang, Young-Chae
    • Korean Journal of Food Science and Technology
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    • v.50 no.1
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    • pp.105-110
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    • 2018
  • Melittin is the main component of apitoxin (bee venom) that has been reported to have anti-inflammatory and anti-cancer effects. Herein, we demonstrated that inhibition of epithelial-mesenchymal transition (EMT) by melittin causes suppression of cancer cell migration and invasion. Melittin significantly suppressed the epidermal growth factor (EGF)-induced cell migration and invasion in lung cancer cells. Moreover, melittin up-regulated the expression of epithelial marker protein, E-cadherin, and down-regulated the expression of EMT related proteins, vimentin and fibronectin. Mechanistic studies revealed that melittin markedly suppressed the expression of EMT mediated transcription factors, ZEB2, Slug, and Snail. The EGF-induced phosphorylation of AKT, mTOR, P70S6K, and 4EBP1 was also inhibited by melittin, but not that of ERK and JNK. Therefore, the inhibitory effect of melittin on migration and invasion of lung cancer cells may be associated with the inhibition of EMT via blocking of the AKT-mTOR-P70S6K-4EBP1 pathway.

Isolation and characterization of Auxin/indole-3-acetic acid 1 (Aux/IAA1) gene from poplar (Populus alba × P. glandulosa) (현사시나무에서 Auxin/indole-3-acetic acid 1 (Aux/IAA1) 유전자 분리 및 발현 특성 구명)

  • Bae, Eun-Kyung;Choi, Young-Im;Lee, Hyoshin;Choi, Ji Won
    • Journal of Plant Biotechnology
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    • v.46 no.3
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    • pp.180-188
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    • 2019
  • Auxin plays a crucial regulatory role in plant growth and development processes. Three major classes of auxin-responsive transcription factors controlled by the Auxin/indole-3-acetic acid (Aux/IAA), Gretchen Hagen 3 (GH3), and small auxin up RNA (SAUR) genes regulate auxin signaling. Aux/IAA, in particular, encodes short-lived nuclear proteins that accumulate rapidly in response to auxin signaling. In this study, we isolated a PagAux/IAA1 gene from poplar (Populus alba ${\times}$ P. glandulosa) and investigated its expression characteristics. The PagAux/IAA1 cDNA codes for putative 200 amino acids polypeptide containing four conserved domains and two nuclear localization signals (NLSs). Utilizing Southern blot analysis, we confirmed that a single copy of the PagAux/IAA1 gene was present in the poplar genome. The expression of this gene is specific to leaves and flowers of the poplar. PagAux/IAA1 expressed in the early exponential growth phase of cell-cultured in suspension. PagAux/IAA1 expression level reduced in drought and salt stress conditions, and the presence of plant hormones such as abscisic acid. However, expression enhanced in cold stress, cambial cell division, and presence of plant hormones such as gibberellic acid and jasmonic acid. Thus, these results suggest that PagAux/IAA1 participates in cold stress response as well as developmental processes in the poplar.

Conservative Genes among 1,309 Species of Prokaryotes (원핵생물 1,309종의 보존적 유전자)

  • Lee, Dong-Geun
    • Journal of Life Science
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    • v.32 no.6
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    • pp.463-467
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    • 2022
  • As a result of applying the COG (Cluster of Orthologous Groups of Protein) algorithm to 1,309 species to confirm the conserved genes of prokaryotes, ribosomal protein S11 (COG0100) was identified. The numbers of conservative genes were 2, 5, 5, and 6 in 1,308, 1,307, 1,306, and 1,305 species, respectively. Twenty-nine genes were conserved in over 1,302 species, and they encoded 23 ribosomal proteins, 3 tRNA synthetases, 2 translation factors, and 1 RNA polymerase subunit. Most of them were related to protein production, suggesting the importance of protein expression in prokaryotes. The highest conservative COG was COG0048 (ribosomal protein S12) among the 29 COGs. The 29 conserved genes usually have one protein for each prokaryote. COG0090 (ribosomal protein L2) had not only the lowest conservation value but also the largest standard deviation of phylogenetic distance value. As COG0090 is not only a member of the ribosome, but also a regulator of replication and transcription, it could be inferred that prokaryotes have large variations in COG0090 to survive in various environments. This study could provide data necessary for basic science, tumor control, and development of antibacterial agents.

Involvement of Multiple Signaling Molecules in Peptidoglycan-induced Expression of Interleukin-1α in THP-1 Monocytes/Macrophages (THP-1 단핵구의 펩티도글리칸 유래 인터루킨-1 알파 발현에서 TLR2, PI3K/Akt/mTOR, MAPKs의 역할)

  • Heo, Weon;Son, Yonghae;Cho, Hyok-rae;Kim, Koanhoi
    • Journal of Life Science
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    • v.32 no.6
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    • pp.421-429
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    • 2022
  • The expression of interleukin-1α (IL-1α) is elevated in monocytic cells, such as monocytes and macro-phages, within atherosclerotic arteries, yet the cellular molecules involved in cytokine upregulation remain unclear. Because peptidoglycan (PG), a major component of gram-positive bacterial cell walls, is detected within the inflammatory cell-rich regions of atheromatous plaques, it was investigated if PG contributes to IL-1α expression in monocytes/macrophages. Exposure of THP-1 monocytic cells to PG resulted in elevated levels of IL-1α gene transcripts and increased secretion of IL-1α protein. The transcription and secretion of IL-1α were abrogated by OxPAPC, an inhibitor of TLR2/4, but not by polymyxin B that inhibits lipopolysaccharide-induced TLR4 activation. To understand the molecular mechanisms of the inflammatory responses due to bacterial pathogen-associated molecular patterns (PAMPs) in diseased arteries, we attempted to determine the cellular factors involved in the PG-induced upregulation of IL-1α expression. Pharmacological inhibition of cell signaling pathways with LY294002 (a PI3K inhibitor), Akti IV (an inhibitor of Akt activation), rapamycin (an mTOR inhibitor), U0126 (a MEK inhibitor), SB202190 (a p38 MAPK inhibitor), SP6001250 (a JNK inhibitor), and DPI (a NOX inhibitor) also significantly attenuated the PG-mediated expression of IL-1α. These results suggest that PG induces the monocytic or macrophagic expression of IL-1α, thereby contributing to vascular inflammation, via multiple signaling molecules, including TLR2, PI3K/Akt/mTOR, and MAPKs.

Defatted Grape Seed Extracts Suppress Adipogenesis in 3T3-L1 Preadipocytes (포도씨 탈지박 추출물 처리가 3T3-L1 Preadipocyte 내 지방 생성에 미치는 영향)

  • Cho, Young-Min;Lee, Seon-Mi;Kim, Young-Hwa;Jeon, Geon-Uk;Sung, Jee-Hy;Jeong, Heon-Sang;Lee, Jun-Soo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.6
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    • pp.927-931
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    • 2010
  • The objective of this study was to evaluate the effect of defatted grape seed extract (DGSE) on adipocyte differentiation in 3T3-L1 preadipocytes. DGSE at 100 ${\mu}g$/mL significantly suppressed lipid accumulation and glycerol-3-phosphate dehydrogenase activity in hormonally stimulated adipocytes, an indicator of adipocyte differentiation. In order to understand the anti-adipogenic effects of DGSE, the changes in the expression of several adipogenic transcription factors including peroxisome proliferator-activated receptor (PPAR) $\gamma$, CCAAT/enhancer-binding protein (C/EBP) $\alpha$ and $\beta$ were investigated using immunoblotting. DGSE suppressed the expression of PPAR$\gamma$, C/EBP$\alpha$, and C/EBP$\beta$ proteins compared with control adipocytes in a dose-dependent manner. This results indicated that DGSE may alter fat mass by directly affecting adipogensis in maturing preadipocytes and thus may have applications for the treatment of obesity.

The Effects of Supungsunki-hwan on High Fat, High Carbohydrate Diet-induced Obese Type 2 Diabetic Mouse Model (수풍순기환 투여가 고지방, 고탄수화물 식이로 유발된 비만형 제2형 당뇨병 동물모델에 미치는 영향)

  • Park, Jong-Seol;Lee, Byung-Cheol;Doo, Ho-Kyung;Ahn, Young-Min;Ahn, Se-Young
    • The Journal of Internal Korean Medicine
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    • v.30 no.2
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    • pp.257-269
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    • 2009
  • Objective : Obesity is an important cause of diabetes, and lipotoxicity causes insulin resistance. Recently a lot of research is being done on PPAR-${\alpha}$. TNF-${\alpha}$. adiponectin, and leptin, which are important obesity related factors. In this study, we investigated the effects of Supungsunki-hwan on high fat. high carbohydrate diet-induced obese type 2 diabetic mouse models. Methods: Diabetes was induced in ICR male mouse (30${\pm}$5g) with Surwit's high fat, high sucrose diet. Mice were divided into 4 groups(n=10) of Normal. Control. Supungsunkj-hwan group. and acarbose group. The Supungsunki-hwsn group was given 10% Supungsunkj-hwan in their diet. and the acarbose group was given 0.5% acarbose in their diet. After 6 weeks. body weight. food intake, FBS and OGTT. lipid profile and liver enzymes, epididymal fat weight, and gene expression of leptin, adiponectin, TNF-${\alpha}$ and PPAR-${\alpha}$ were measured. Leptin. adiponectin. tumor necrosis factor(TNF)-${\alpha}$ and peroxisome proliferator-activated receptor (PPAR)-${\alpha}$ were evaluated by reverse transcription-polymerase chain reaction. Results : Supungsunkj-hwan increased the gene expression of PPAR-${\alpha}$, which reduces lipotoxicity and insulin resistance. Supungsunkj-hwan also significantly reduced triglyceride. AST. ALT serum levels. and 1 hour oral glucose tolerance levels. Conclusion : These results show that Supungsunkj-hwan improves insulin resistance in the liver and muscles, by reducing triglyceride levels and lipotoxicity through increased PPAR-${\alpha}$ gene expression. This is supported by the fact that Supungsunkj-hwan significantly reduces 1 hour oral glucose tolerance levels. Therefore we suggest that Supungsunkj-hwan would be an effective treatment for obese type 2 diabetic patients.

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Identification of Introduced Gene and Its Expression and Gene Stability Assessment for Event Selection of Genetically Modified Plant toward Approval: Cucumber Mosaic Virus Resistant Hot Pepper (상업용 유전자 변형작물 이벤트 선발을 위한 도입유전자 확인, 발현 및 세대간 안정성 평가 : 오이모자이크바이러스 저항성 GM 고추)

  • Kang, Seung-Won;Han, Bal-Kum;Lee, Tae-Ho;Kim, Eun-Ji;Lee, Gung-Pyo
    • Horticultural Science & Technology
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    • v.30 no.2
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    • pp.192-200
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    • 2012
  • For the development of genetically modified plants, it is important to verify various factors which potentially affect the risk assessment as well as to establish an experimental program to produce scientific and reliable data. However, it is a time and cost consuming process to develop GM plants as well as to prepare scientific and convincible data for government's approval. Therefore, using the transgenic hot pepper tolerant to a new CMV pathotype, we attempted to suggest few methodological procedures, such as probe saturation for southern blot analysis and RT-PCR and ELISA for expression analysis, for identification and stability evaluation of inserted gene in genetically modified plant which are required for submission for approval. Ten partially overlapped probes covering full length of inserted gene were produced. We could identify that the inserted gene was stacked as a single copy as well as no partial element existed. Also, we could identify the stability of the inserted gene stacked in hot pepper using probe saturation. In the expression analysis with RT-PCR and ELISA, we also could provide the stable expression of transcript and proteins in leaves and placenta and pericarp of fruits of the CMV-resistant hot pepper.

Correlation between Changes in Microbial/Physicochemical Properties and Persistence of Human Norovirus during Cabbage Kimchi Fermentation

  • Lee, Hee-Min;Lee, Ji-Hyun;Kim, Sung Hyun;Yoon, So-Ra;Lee, Jae Yong;Ha, Ji-Hyoung
    • Journal of Microbiology and Biotechnology
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    • v.27 no.11
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    • pp.2019-2027
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    • 2017
  • Recently, cabbage kimchi has occasionally been associated with the foodborne diseases of enteric viruses such as human norovirus (HuNoV). This study aimed to evaluate the correlation between microbial/physicochemical properties and persistence of HuNoV in experimentally contaminated cabbage kimchi fermented and stored at $4^{\circ}C$ or $10^{\circ}C$ for 28 days. Changes in organic acid content, lactic acid bacteria (LAB), acidity, pH, and salinity were analyzed. The recovery of structurally intact HuNoV was examined for up to 28 days post-inoculation, using a NoV GII.4 monoclonal antibody-conjugated immuno-magnetic separation method combined with quantitative real-time reverse transcription polymerase chain reaction. On day 0, LAB loads were $4.70log_{10}$ colony forming units/g and HuNoV GII.4 titers were $2.57log_{10}\;genomic\;copies/{\mu}l$, at both temperatures. After 28 days, intact HuNoV titers decreased to 1.58 ($4^{\circ}C$) and $1.04(10^{\circ}C)log_{10}\;genomic\;copies/{\mu}l$, whereas the LAB density increased. This correlated with a gradual increase in lactic acid and acetic acid at both temperatures. Our findings support a statistical correlation between changes in physicochemical properties and the recovery of structurally intact HuNoV GII.4. Moreover, we determined that the production of organic acid and low pH could affect HuNoV GII.4 titers in cabbage kimchi during fermentation. However, HuNoV GII.4 was not completely eliminated by microbial/physicochemical factors during fermentation, although HuNoV GII.4 was reduced. Based on this, we speculate that the persistence of HuNoV GII.4 may be affected by the continually changing conditions during kimchi fermentation.