• Molecules and Cells
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• v.41 no.5
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• pp.444-453
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• 2018

Aberrations in histone modifications are being studied in mixed-lineage leukemia (MLL)-AF9-driven acute myeloid leukemia (AML). In this study, we focused on the regulation of the differentiation of the MLL-AF9 type AML cell line THP-1. We observed that, upon phorbol 12-myristate 13-acetate (PMA) treatment, THP-1 cells differentiated into monocytes by down-regulating Aurora kinase A (AURKA), resulting in a reduction in H3S10 phosphorylation. We revealed that the AURKA inhibitor alisertib accelerates the expression of the H3K27 demethylase KDM6B, thereby dissociating AURKA and YY1 from the KDM6B promoter region. Using Flow cytometry, we found that alisertib induces THP-1 differentiation into monocytes. Furthermore, we found that treatment with the KDM6B inhibitor GSK-J4 perturbed the PMA-mediated differentiation of THP-1 cells. Thus, we discovered the mechanism of AURKA-KDM6B signaling that controls the differentiation of THP-1 cells, which has implications for biotherapy for leukemia.

• Preventive Nutrition and Food Science
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• v.4 no.4
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• pp.260-264
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• 1999

Korean traditional fermented soy paste (doenjang) prolonged the life span of Balb/c mice injected with the sarcoma-180 cells. The activities of liver enzymes, such as xanthine oxidase, aminopyrine N-demethylase, aniline hydroxylase, ${\gamma}$-glutamylcysteine synthetase, glutathione reductase and glutathione S-transferase (GST), and the contents of lipid peroxide and glutathione were determined from the sarcoma-180 cell injected mice that were treated with methanol extracts from doenjang, miso and soybean. The content of lipid peroxide and the activity of xanthine oxidase in the liver of Balb/c mice which were increased by the transplantation of the sarcoma-180 cells were decreased by treatment with the methanol extract from doenjang. But the activities of aminopyrine N-dementhylase and aniline hydroxylase were not affected by the treatment of methanol extracts from doenjang to the mice injected with the sarcoma-180 cells. The content of glutathione, the activities of glutamylcysteine synthetase, glutathione reductase and glutathione S-transferase decreased by the injection of the sarcoma-180 were recovered considerably by the treatment of the methanol extract from doenjang.

• Korean Journal of Pharmacognosy
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• v.28 no.4
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• pp.239-246
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• 1997

The methanol extracts of some marine algae were tested for investigating the effects on the formation of lipid peroxide and the activities of free radical generating enzyme in vitro in bromobenzene-treated rat. The extracts of Enteromorpha compressa, Capsosiphon fulvescens, Gelidium amansii, Hizikia fusiformis, Sargassum siliquastrum and Sargassum thunbergii which decreased the formation of lipid peroxide, inhibited the activity of xanthine and aldehyde oxidases by adding of each extracts. Phloroglucinol isolated from Ecklonia stolonifera reduced bromobenzene-induced hepatic lipid peroxidation. This compound administered daily over one week before intoxication with bromobenzene did not affect the activities of aminopyrine N-demethylase, aniline hydroxylase and glu tathione S-transferase. Epoxide hydrolase activity was decreased by bromobenzene, which was restored by pretreatment of phloroglucinol, The results suggest that the bromobenzene-induced hepatic lipid peroxidation by phloroglucinol is reduced by enhancing the activity of epoxide hydrolase.

• Molecules and Cells
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• v.27 no.4
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• pp.481-490
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• 2009

Diverse posttranslational modifications of histones, such as acetylation and methylation, play important roles in controlling gene expression. Histone methylation in particular is involved in a broad range of biological processes, including heterochromatin formation, X-chromosome inactivation, genomic imprinting, and transcriptional regulation. Recently, it has been demonstrated that proteins containing the Jumonji (Jmj) C domain can demethylate histones. In Arabidopsis, twenty-one genes encode JmjC domain-containing proteins, which can be clustered into five clades. To address the biological roles of the Arabidopsis genes encoding JmjC-domain proteins, we analyzed the temporal and spatial expression patterns of nine genes. RT-PCR analyses indicate all nine Arabidopsis thaliana Jmj (AtJmj) genes studied are actively expressed in various tissues. Furthermore, studies of transgenic plants harboring AtJmj::${\beta}$-glucuronidase fusion constructs reveal that these nine AtJmj genes are expressed in a developmentally and spatially regulated manner.

• Archives of Pharmacal Research
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• v.24 no.6
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• pp.536-540
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• 2001

Hepatic lipid peroxide contents were examined in bromobenzene-treated rats firstly after the oral administration of MeOH extract of Kalopanax pictus stem bark its n-BuOH fraction, EtOAc fraction and an alkaline hydrolysate of the n-BuOH fraction, and secondly after the intraperitoneal administration of hederagenin monodesmosides and bisdesmosides. Two hederagenin monodesmosides, kalopanaxsaponin A (KPS-A) and sapindoside C, exhibited significant anti-lipid peroxidation effects after intraperitoneal administration at doses of $10-30{\;}{\mu}mole/kg$, whereas their bisdesmosides did not exhibit any significant activity. These results suggest that it is the hederagenin monodesmosides that are responsible for anti-lipid peroxidation in vivo. The activity of KPS-A was established by the observation of decreased aminopyrine N-demethylase activity and increased epoxide hydrolase activity.

• Archives of Pharmacal Research
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• v.28 no.12
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• pp.1386-1391
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• 2005

This study examined the role of Kupffer cells in altering the hepatic secretory and microsomal function during ischemia and reperfusion (ls/Rp). Rats were subjected to 60 min of hepatic ischemia, followed by 1 and 5 h of reperfusion. Gadolinium chloride ($GdCl_{3}$, 7.5 mg/kg body weight, intravenously) was used to inactivate the Kupffer cells 1 day prior to ischemia. Is/Rp markedly increased the serum aminotransferase level and the extent of lipid peroxidation. $GdCl_{3}$ significantly attenuated these increases. Is/Rp markedly decreased the bile. flow and cholate output, and $GdCl_{3}$ restored their secretion. The cytochrome P450 content was decreased by Is/Rp. However, these decreases were not prevented by $GdCl_{3}$. The aminopyrine N-demethylase activity was decreased by Is/Rp, while the aniline p-hydroxylase activity was increased. $GdCl_{3}$ prevented the increase in the aniline p-hydroxylase activity. Overall, Is/Rp diminishes the hepatic secretory and microsomal drug-metabolizing functions, and Kupffer cells are involved in this hepatobiliary dysfunction.

• BMB Reports
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• v.54 no.10
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• pp.522-527
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• 2021

Lysine-specific demethylase 1 (LSD1) is an epigenetic regulator that modulates the chromatin status, contributing to gene activation or repression. The post-translational modification of LSD1 is critical for the regulation of many of its biological processes. Phosphorylation of serine 112 of LSD1 by protein kinase C alpha (PKCα) is crucial for regulating inflammation, but its physiological significance is not fully understood. This study aimed to investigate the role of Lsd1-S112A, a phosphorylation defective mutant, in the cigarette smoke extract/LPS-induced chronic obstructive pulmonary disease (COPD) model using Lsd1^SA/SA mice and to explore the potential mechanism underpinning the development of COPD. We found that Lsd1^SA/SA mice exhibited increased susceptibility to CSE/LPS-induced COPD, including high inflammatory cell influx into the bronchoalveolar lavage fluid and airspace enlargement. Additionally, the high gene expression associated with the inflammatory response and oxidative stress was observed in cells and mice containing Lsd1-S112A. Similar results were obtained from the mouse embryonic fibroblasts exposed to a PKCα inhibitor, Go6976. Thus, the lack of LSD1 phosphorylation exacerbates CSE/LPS-induced COPD by elevating inflammation and oxidative stress.

• Molecules and Cells
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• v.42 no.7
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• pp.530-545
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• 2019

Tumor cells can vary epigenetically during ionizing irradiation (IR) treatment. These epigenetic variegations can influence IR response and shape tumor aggressiveness. However, epigenetic disturbance of histones after IR, implicating in IR responsiveness, has been elusive. Here, we investigate whether altered histone modification after IR can influence radiation responsiveness. The oncogenic CXCL12 mRNA and protein were more highly expressed in residual cancer cells from a hepatoma heterotopic murine tumor microenvironment and coculture of human hepatoma Huh7 and normal IMR90 cells after radiation. H3K4 methylation was also enriched and H3K9 methylation was decreased at its promoter region. Accordingly, invasiveness and the subpopulation of aggressive $CD133^+/CD24^-$ cells increased after IR. Histone demethylase inhibitor IOX1 attenuated CXCL12 expression and the malignant subpopulation, suggesting that responses to IR can be partially mediated via histone modifications. Taken together, radiation-induced histone alterations at the CXCL12 promoter in hepatoma cells are linked to CXCL12 upregulation and increased aggressiveness in the tumor microenvironment.

• Journal of the Korean Data and Information Science Society
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• v.19 no.3
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• pp.937-949
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• 2008

The purpose of this meta-analysis was to investigate the anti-hepatotoxic effect of ginseng in rats induced with CC14 or TCDD, the toxicities that cause liver damages. Primary studies were collected from the ScienceDirect database, the DBpia, and the KISS. The data on the effect factors in plasma and in enzyme are listed as many as possible: The effect factors were alanine transaminase(ALT), aspartate transaminase(AST), liver aminopyrine N-demethylase(AD), liver aniline hydroxylase(AH), liver 3,4-Methylenedioxyamphetamine(liver MDA), cytochrome P450(P450), serum alkaline phosphatase(ALP), serum lactate dehydrogenase(LDH), cytochrome b5(Cyto b5), glutathione reductase (GR), Liver glutathione S-transferase(GST), liver glutamyltransferase (GT), Liver($\gamma$-GCS), serum liver 3,4-Methylenedioxyamphetamine(serum MDA), serum sorbitol dehydrogenase(SDH), serum total protein(TP), and serum $\gamma$-glutamyltransferase($\gamma$-GT). In order to investigate the effect of ginseng, the standard mean difference(HG) between the group of rats induced with toxicity(RH) and the group of rats induced with ginseng(RHG) were combined, and the significance of HGs were tested. The combined HGs checked the biases caused by heterogeneity among studies and the publication biases. Then they were adjusted by using the random effect model and trim and fill method. Although the publication biases were assumed, among all plasma factors the HGs of ALT, AST, serum MDA, SDH, TP, and $\gamma$-GT were significant, and among all enzyme factors the HGs of liver MDA, Cyto b5, GR, GST, and GT were significant. The treatment with ginseng significantly affected the plasma and enzyme levels in rats induced with toxicity.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2005.09a
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• pp.139-143
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• 2005

Cytochrome P450 14${\alpha}$-sterol demethylase enzyme (CYP51) is the target a of azole type antifungals. The azole blocks the ergosterol synthesis and thereby inhibits fungal growth. A three-dimensional (3D) homology model of CYP51 from Candida albicans was constructed based on the X-ray crystal structure of CYP51 from Mycobacterium tuberculosis. Using this model, the binding modes for the substrate (24-methylene-24, 25-dihydrolanosterol) and the known inhibitors (fluconazole, voriconazole, oxiconazole, miconazole) were predicted from docking. Virtual screening was performed employing Structure Based Focusing (SBF). In this procedure, the pharmacophore models for database search were generated from the protein-ligands interactions each other. The initial structure-based virtual screening selected 15 compounds from a commercial available 3D database of approximately 50,000 molecule library, Being evaluated by a cell-based assay, 5 compounds were further identified as the potent inhibitors of Candida albicans CYP51 (CACYP51) with low minimal inhibitory concentration (MIC) range. BMD-09-01${\sim}$BMD-09-04 MIC range was 0.5 ${\mu}$g/ml and BMD-09-05 was 1 ${\mu}$g/ml. These new inhibitors provide a basis for some non-azole antifungal rational design of new, and more efficacious antifungal agents.