• Title/Summary/Keyword: downregulation

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Inhibition of SIRT1 Sensitizes TRAIL-Resistant MCF-7 Cells by Upregulation of DR5 and Inhibition of c-FLIP (SIRT1 억제에 의한 DR5 발현증강과 c-FLIP 발현저해 작용으로 사람유방암세포 MCF-7의 TRAIL 감수성 증강)

  • Lee, Su-Hoon;Kim, Hak-Bng;Kim, Mi-Ju;Lee, Jae-Won;Bae, Jae-Ho;Kim, Dong-Wan;Kang, Chi-Dug;Kim, Sun-Hee
    • Journal of Life Science
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    • v.22 no.10
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    • pp.1277-1285
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    • 2012
  • The tumor necrosis, factor-related, apoptosis-inducing ligand (TRAIL) is regarded as a potentially useful anticancer agent with excellent selectivity for cancer cells. However, a considerable number of cancer cells are resistant to apoptosis induction by TRAIL. Developing strategies to overcome this resistance are important for the successful use of TRAIL for cancer therapy. Here, we revealed that siRNA-mediated downregulation of SIRT1 or SIRT1 inhibitor Amurensin G upregulated DR5 and c-Myc and downregulated c-$FLIP_{L/S}$ and Mcl-1, which was associated with sensitization of TRAIL-resistant MCF-7 cells to TRAIL. This result was followed by the activation of caspases, PARP cleavage, and downregulation of Bcl-2 in both TRAIL-treated MCF-7 cells transfected with SIRT1 siRNA and cells co-treated with Amurensin G and TRAIL. Our results suggest that the induction of DR5 and downregulation of c-FLIP via suppression of SIRT1 expression may be a useful strategy to increase the susceptibility of TRAIL-resistant cancer cells to TRAIL-induced cell death.

Downregulation of EHT1 and EEB1 in Saccharomyces cerevisiae Alters the Ester Profile of Wine during Fermentation

  • Yang, Xue;Zhang, Xuenan;He, Xi;Liu, Canzhen;Zhao, Xinjie;Han, Ning
    • Journal of Microbiology and Biotechnology
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    • v.32 no.6
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    • pp.761-767
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    • 2022
  • EHT1 and EEB1 are the key Saccharomyces cerevisiae genes involved in the synthesis of ethyl esters during wine fermentation. We constructed single (Δeht1, Δeeb1) and double (Δeht1Δeeb1) heterogenous mutant strains of the industrial diploid wine yeast EC1118 by disrupting one allele of EHT1 and/or EEB1. In addition, the aromatic profile of wine produced during fermentation of simulated grape juice by these mutant strains was also analyzed. The expression levels of EHT1 and/or EEB1 in the relevant mutants were less than 50% of the wild-type strain when grown in YPD medium and simulated grape juice medium. Compared to the wild-type strain, all mutants produced lower amounts of ethyl esters in the fermented grape juice and also resulted in distinct ethyl ester profiles. ATF2, a gene involved in acetate ester synthesis, was expressed at higher levels in the EEB1 downregulation mutants compared to the wild-type and Δeht1 strains during fermentation, which was consistent with the content of acetate esters. In addition, the production of higher alcohols was also markedly affected by the decrease in EEB1 levels. Compared to EHT1, EEB1 downregulation had a greater impact on the production of acetate esters and higher alcohols, suggesting that controlling EEB1 expression could be an effective means to regulate the content of these aromatic metabolites in wine. Taken together, the synthesis of ethyl esters can be decreased by deleting one allele of EHT1 and EEB1 in the diploid EC1118 strain, which may modify the ester profile of wine more subtly compared to the complete deletion of target genes.

Synthesis of Novel Pyrazolinecarbothioamide and Evaluation of Its Anti-Cancer Activity (새로운 피라졸린카르보티오아미드 화합물의 합성과 항암효과)

  • Koh, Dongsoo
    • Journal of Applied Biological Chemistry
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    • v.55 no.3
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    • pp.191-194
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    • 2012
  • Novel pyrazolinecarbothioamide (5) was synthesized from chalcone (3) which was prepared from 2'-hydroxy-1'-acetonaphthone (1) and 2-methoxy benzaldehyde (2). Treatment of pyrazolinecarbothioamide (5) on HCT116 cancer cell showed upregulation of p21 and downregulation of cyclin D1 protein. Flowcytometer analysis revealed that pyrazolinecarbothioamide (5) controls the expression of cell cycle regulatory proteins, which blocks cell cycle progression of HCT116 cancer cell at the G1 phase.

Bisphenol A-induced overall immune downregulation in mice

  • Byun, Jung-A;Pyo, Myoung-Yun
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.118.2-119
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    • 2003
  • This study was undertaken to assess overall effects of bisphenol A, a monomer widely used in manufacturing polycarbonate plastics or epoxy resin, exposure on immune system of mice. For in vitro evaluation, serial concentration of SPA was added into culture of various immune cells from normal female ICR mice, and for in vivo or ex vivo assessment, mice were orally exposed to BPA dissolved in olive oil as doses of 500, 1000, 2000 mg/g b.w. for acute expose or 100, 500, 1000 mg/kg/day b.w. 5days a week for subacute exposure. (omitted)

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Estrogen receptor is downregulated by expression of HIF-1a/VP16

  • Cho, Jung-Yoon;Lee, Young-Joo
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.228.2-229
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    • 2003
  • Estrogen Receptor is a ligand-activated transcription factor. The concentration of the receptor is a major component that regulates expression of estrogen-responsive genes. We have studied mechanism of estrogen receptor alpha (ER${\alpha}$) downregulation by HIF-1 using HIF-1${\alpha}$/VP16 constructs. ER${\alpha}$ is known to be downregulated under hypoxic condition. Transcriptional response under hypoxia is mediated through Hypoxia-inducible factor-1 (HIF-1), a transcription factor that is usullaly degraded but stabilized under hypoxia. (omitted)

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Downregulation of inducible nitric oxide synthase expression by a ceramide analogue in RAW 264.7 murine macrophages

  • Park, Sung-Sik;Chulbu Yim;Kim, Mie-Young;Chun, Young-Jin
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2003.05a
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    • pp.50-50
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    • 2003
  • Nitric oxide (NO) has been studied and found to be an important intracellular modulator. The excess NO produced by the inducible nitric-oxide synthase (iNOS) is implicated in various inflammatory diseases and cellular injury. Inflammatory cytokines such as TNF- or IL-6 increase intracellular ceramide and ceramide may induce NO production and inflammation. (omitted)

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Chemopreventive Allylthiopyridazines, K compounds, Inhibit Invasion, Migration and Angiogenesis in SK-Hep-1 Hepatocarcinoma Cells Possibly via MMP-2 Downregulation

  • Lee, Eun-Jung;Shin, Ilc-Hung;Kwon, Soon-Kyung
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.218.1-218.1
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    • 2003
  • Dietary organosulfur compounds have been shown to inhibit the proliferation of tumor cells. Synthetic sulfur-containing compounds including oltipraz exert chemopreventive and hepatoprotective effects. We previously showed that synthetic allylthiopyridazine derivatives designated as K compounds induced apoptosis in SK-Hep-1 hepatocarcinoma cells (Eur. J. Cancer: 37, 2104-10, 2001). (omitted)

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GATA4 negatively regulates osteoblast differentiation by downregulation of Runx2

  • Song, Insun;Kim, Kabsun;Kim, Jung Ha;Lee, Young-Kyoung;Jung, Hyun-Jung;Byun, Hae-Ok;Yoon, Gyesoon;Kim, Nacksung
    • BMB Reports
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    • v.47 no.8
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    • pp.463-468
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    • 2014
  • Osteoblasts are specialized mesenchymal cells that are responsible for bone formation. In this study, we examine the role of GATA4 in osteoblast differentiation. GATA4 was abundantly expressed in preosteoblast cells and gradually down-regulated during osteoblast differentiation. Overexpression of GATA4 in osteoblastic cells inhibited alkaline phosphatase activity and nodule formation in osteogenic conditioned cell culture system. In addition, overexpression of GATA4 attenuated expression of osteogenic marker genes, including Runx2, alkaline phosphatase, bone sialoprotein, and osteocalcin, all of which are important for osteoblast differentiation and function. Overexpression of GATA4 attenuated Runx2 promoter activity, whereas silencing of GATA4 increased Runx2 induction. We found that GATA4 interacted with Dlx5 and subsequently decreased Dlx5 binding activity to Runx2 promoter region. Our data suggest that GATA4 acts as a negative regulator in osteoblast differentiation by downregulation of Runx2.