• Proceedings of the Korea Society of Environmental Toocicology Conference
• /
• 2002.10a
• /
• pp.170-170
• /
• 2002

College of Pharmacy, Ewha womans University, Seoul, 120-750, Korea 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent halogenated aromatic hydrocarbon congener that induces expression of several genes including CYP1A1. Exposure to TCDD results in many toxic actions such as carcinogenesis, hepatotoxicity, immune suppression, and reproductive and developmental toxicity. Dramatic differences in dioxin toxicity have been observed between the sexes of some animal species, suggesting hormonal modulation of dioxin action. Many studies have been reported and propose several mechanisms of anti-estrogenic effects of TCDD. In contrast, the effect of estrogen on the regulation of CYP1A1 are not clear at present. There are several reports showing conflicting results. It seems that induction/inhibition of CYP1A1 may be dependent on cell-type and concentration. The purpose of this study was to investigate the regulation of TCDD-induced CYP1A1 gene expression by estradiol and its metabolites. We examined whether estradiol and its metabolites altered TCDD-mediated induction of CYP1A1 enzyme activity. 17 ${\beta}$ estradiol and 16 ${\alpha}$ estriol at non cytotoxic concentrations caused a significant concentration dependent decline of TCDD-induced EROD activity To determine whether reduced EROD activity reflected altered CYP1A1 mRNA expression, we measured CYP1A1 mRNA level by RT-PCR. And to examine whether estradiol and its metabolites have effects on TCDD-induced CYP1A1 gene expression at the transcription level, we also peformed transient transfection with an AhR responsive reporter plasmid containing the 5' flanking region of the human CYP1A1 gene to examine whether estradiol and its metabolites have effects on TCDD-induced CYP1A1 gene expression at the transcription level.

• Biomolecules & Therapeutics
• /
• v.20 no.1
• /
• pp.57-61
• /
• 2012

The matrix metalloproteinase (MMP) family is involved in the breakdown of the extracellular matrix during normal physiological processes such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes such as pathological aging, arthritis, and metastasis. Oxidative conditions generate reactive oxygen species (ROS) (e.g., hydrogen peroxide [$H_2O_2$]) in cells, which subsequently induce the synthesis of matrix metalloproteinase-1 (MMP-1). MMP-1, an interstitial collagenase, in turn stimulates an aging phenomenon. In this study, baicalein (5,6,7-trihydroxyfl avone) was investigated for its in vitro activity against $H_2O_2$-induced damage using a human skin keratinocyte model. Baicalein pretreatment signifi cantly inhibited $H_2O_2$-induced up-regulation of MMP-1 mRNA, MMP-1 protein expression and MMP-1 activity in cultured HaCaT keratinocytes. In addition, baicalein decreased the transcriptional activity of activator protein-1 (AP-1) and the expression of c-Fos and c-Jun, both components of the heterodimeric AP-1 transcription factor. Furthermore, baicalein reduced phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinase (JNK), which are upstream of the AP-1 transcription factor. The results of this study suggest that baicalein is involved in the inhibition of oxidative stress-induced expression of MMP-1 via inactivation of the ERK/JNK/AP-1 signaling pathway.

• Molecules and Cells
• /
• v.26 no.3
• /
• pp.285-290
• /
• 2008

Estrogen-induced proliferation in estrogen receptor (ER)-positive breast cancer cells is primarily mediated through two distinct intracellular receptors, $ER{\alpha}$ and $ER{\beta}$. Although tumor necrosis factor alpha ($TNF{\alpha}$) and $E2/ER{\alpha}$ are known to exert opposing effects on cell proliferation in MCF-7 cells, the mechanism by which $TNF{\alpha}$ antagonizes $E2/ER{\alpha}$-mediated cell proliferation is not well understood. The present study suggests that reduced cell survival in response to $TNF{\alpha}$ treatment in MCF-7 cells may be associated with the down-regulation of $ER{\alpha}$ protein. The decrease in $ER{\alpha}$ protein level was accompanied by an inhibition of $ER{\alpha}$ gene transcription. Cell viability was decreased synergistically by the combined treatment with $ER{\alpha}$-siRNA and $TNF{\alpha}$. Furthermore, pretreatment of cells with the PI3-kinase (PI3K)/ Akt inhibitor, LY294002, markedly enhanced $TNF{\alpha}$-induced down-regulation of the $ER{\alpha}$ protein, suggesting that the PI3K/Akt pathway might be involved in control of the $ER{\alpha}$ level. Moreover, down-regulation of $ER{\alpha}$ by $TNF{\alpha}$ was not inhibited in cells that were pretreated with the proteasome inhibitors, MG132 and MG152, which suggests that proteasome-dependent proteolysis does not significantly influence $TNF{\alpha}$-induced down-regulation of $ER{\alpha}$ protein. In contrast, the effect of the PI3K/Akt inhibitor on $ER{\alpha}$ was blocked in cells that were treated with LY294002 in the presence of the proteasome inhibitors. Collectively, our findings show that the $TNF{\alpha}$ may partly regulate the growth of MCF-7 breast cancer cells through the down-regulation of $ER{\alpha}$ expression, which is primarily mediated by a PI3K/Akt signaling.

• Journal of Marine Bioscience and Biotechnology
• /
• v.1 no.4
• /
• pp.305-310
• /
• 2006

Abnormal activation of the Wnt/${\beta}$-catenin pathway and subsequent up-regulation of ${\beta}$-catenin response transcription (CRT) are associated with the development of colon cancer. Thus, the Wnt/${\beta}$-catenin pathway is an attractive target for chemoprevention and treatment of this cancer. In this study, we used a cell-based screen to identify a methanol extract of Dictyota dichotoma (EDD) that suppresses the Wnt/${\beta}$-catenin pathway without altering the level of ${\beta}$-catenin protein and reduces the expression of cyclin D1, which is a known ${\beta}$-catenin/T cell factor (TCF)-dependent gene. EDD inhibited the growth of various colon cancer cells. Our findings suggest that EDD can potentially be used as a chemopreventive agent against colon cancer.

• Journal of Life Science
• /
• v.22 no.11
• /
• pp.1515-1522
• /
• 2012

The phytohormone abscisic acid (ABA) plays an important role in the adaptive response of plants to abiotic stresses. ABA also regulates many important processes, including seed dormancy, germination, inhibition of cell division, and stomatal closure. OsABF2 (Oryza sativa ABRE binding factor2) is one of the bZIP type transcription factors, which are involved in abiotic stress response and ABA signaling in rice. Expression of OsABF2 is induced by ABA and various stress treatments. Findings show that survival rates of OsABF2 over-expressing Arabidopsis lines were increased under drought, salt, and heat stress conditions. The germination ratio of OsABF2 over-expressing Arabidopsis lines was decreased in the presence of ABA. Results indicate that OsABF2 over-expressing Arabidopsis lines have enhanced abiotic stress tolerance and have increased ABA sensitivity.

• Journal of Ginseng Research
• /
• v.36 no.2
• /
• pp.146-152
• /
• 2012

Panax ginseng (PG) is a globally utilized medicinal herb. The medicinal effects of PG are primarily attributable to ginsenosides located in the root and leaf. The leaves of PG are known to be rich in various bioactive ginsenosides, and the therapeutic effects of ginseng extract and ginsenosides have been associated with immunomodulatory and anti-inflammatory activities. We examined the effect of PG leaf extract and the isolated ginsenosides, on nuclear factor (NF)-${\kappa}B$transcriptional activity and target gene expression by applying a luciferase assay and reverse transcription polymerase chain reaction in tumor necrosis factor (TNF)-${\alpha}$-treated hepatocarcinoma HepG2 cells. Air-dried PG leaf extract inhibited TNF-${\alpha}$-induced NF-${\kappa}B$transcription activity and NF-${\kappa}B$-dependent cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) gene expression more efficiently than the steamed extract. Of the 10 ginsenosides isolated from PG leaves, Rd and Km most significantly inhibited activity in a dose-dependent manner, with $IC_{50}$ values of $12.05{\pm}0.82$ and $8.84{\pm}0.99\;{\mu}M$, respectively. Furthermore, the ginsenosides Rd and Km inhibited the TNF-${\alpha}$-induced expression levels of the COX-2 and iNOS gene in HepG2 cells. Air-dried leaf extracts and their chemical components, ginsenoside Rd and Km, are involved in the suppression of TNF-${\alpha}$-induced NF-${\kappa}B$ activation and NF-${\kappa}B$-dependent iNOS and COX-2 gene expression. Consequently, air-dried leaf extract from PG, and the purified ginsenosides, have therapeutic potential as anti-inflammatory.

• Journal of Microbiology
• /
• v.42 no.2
• /
• pp.103-110
• /
• 2004

In order to understand the molecular basis of selective expression of stationary-phase genes by RNA polymerase containing$\sigma$$\^$38/ (E$\sigma$$\^$38/) in Escherichia coli, we examined transcription from the stationary-phase promoters, katEP, bo1AP, hdeABP, csgBAP, and mcbP, in vivo and in vitro. Although these pro-moters are preferentially recognized in vivo by E$\sigma$$\^$38/, they are transcribed in vitro by both E$\sigma$$\^$38/ and E$\sigma$$\^$70/ containing the major exponential $\sigma$, $\sigma$$\^$70/. In the presence of high concentrations of glutamate salts, how-ever, oldy E$\sigma$$\^$38/ was able to efficiently transcribe from these promoters, which supports the concept that the promoter selectivity of $\sigma$$\^$38/-containing RNA polymerase is observed only under specific reaction con-ditions. The examination of 6S RNA, which is encoded by the ssr1 gene in vivo, showed that it reduced E$\sigma$$\^$70/ activity during the stationary phase, but this reduction of activity did not result in the elevation of E$\sigma$$\^$38/ activity. Thus, the preferential expression of stationary-phase genes by E$\sigma$$\^$38/ is unlikely the con-sequence of selective inhibition of E$\sigma$$\^$70/ by 6S RNA.

• Microbiology and Biotechnology Letters
• /
• v.42 no.1
• /
• pp.89-92
• /
• 2014

The Wnt/${\beta}$-catenin pathway plays important roles in a variety of biological processes, such as cell proliferation, differentiation, and organ development. Here, we used a cell-based reporter assay to identify bryostatin-1, a natural macrocyclic lactone, as an inhibitor of the Wnt/${\beta}$-catenin pathway. Bryostatin-1 suppressed ${\beta}$-catenin response transcription (CRT), which was activated by a Wnt3a-conditioned medium (Wnt3a-CM), through a decrease in the intracellular ${\beta}$-catenin protein levels, without affecting its mRNA level. In addition, pharmacological inhibition of proteasome abrogated bryostatin-1-mediated down-regulation of the ${\beta}$-catenin protein level. Our findings suggest that bryostatin-1 attenuates the Wnt/${\beta}$-catenin pathway through the promotion of proteasomal degradation of ${\beta}$-catenin.

• Korean Journal of Pharmacognosy
• /
• v.45 no.3
• /
• pp.209-213
• /
• 2014

The anti-melanogenic substance was isolated from the root of Angelica gigas Nakai by silica gel column chromatography, preparative HPLC and TLC. As a result of the structure analysis by mass, $^1H$-NMR, and $^{13}C$-NMR spectrometry, the compound was identified as demethylsuberosin. Demethylsuberosin reduced melanin contents of B16F1 melanoma cells in a dose-dependent manner and decreased to about 74% at a concentration $5{\mu}g/ml$. Demethylsuberosin inhibited the expression in microphthalmia associated transcription factor (MITF), tyrosinase, tyrosinase related protein-1 (TRP-1), and tyrosinase related protein-2 (TRP-2) in melanocytes. These results suggest that the whitening activity of demethylsuberosin may be due to the inhibition of the melanin synthesis by down-regulation of MITF, tyrosinase, TRP-1 and TRP-2 expression. Thus, our results provide evidence that demethylsuberosin might be useful as a potential skin-whitening agent.

• Korean Journal of Microbiology
• /
• v.36 no.3
• /
• pp.236-241
• /
• 2000

A defensin is an inducible antibacterial peptide from a fleshfly and contains 40 residues basic peptide with six cysteines. For the consiruction of recombinant S cerevisiae expressing defensin, the structural gene coding for active defensin was chemically synthesized and fused in fiam to GAP promoter, MFul preprosequence and the GAL7 transcription terminator, generating a recombinant plasnlid pGMD18. S. ce~evisine 2805 Gells were transror~ned to uracil prototroph by the pGMDl8 arid the transformed cells showing antibacterial activity against 111. luteus TAM1056 were selected by growth inhibition zone assay. The optimal culture conditions for the unprovement of the defensin production of a selected tmdonnant were investigated. The optirmzed medium containing 0.4% yeast extract, 2% corn steep liquor, 2.5% glucose and 0.05% $C_2CO_3$, could be determined and the optimum lemperature. and initial pH could be detennnied as $28^{\circ}C$ and pH 3, ~mpectively. The optimized conditioiis revealed the trvofold Increase in the cell growth and the fourfold in the antibaclerial activity. coinpar-ed with tllc Yl'D medium.