• Title/Summary/Keyword: Demethylase

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Vitamin C enhances the expression of IL17 in a Jmjd2-dependent manner

  • Song, Mi Hye;Nair, Varun Sasidharan;Oh, Kwon Ik
    • BMB Reports
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    • v.50 no.1
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    • pp.49-54
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    • 2017
  • Previously, we reported that vitamin C facilitates the CpG demethylation of Foxp3 enhancer in $CD4^+Foxp3^+$ regulatory T cells (Tregs) by enhancing the activity of a DNA demethylase ten-eleven-translocation (Tet). However, it is not clear whether vitamin C affects other helper T cell lineages like T helper type 17 (Th17) cells which are related with Tregs. Here, we show that the expression of interleukin-17A (IL17) increases with the treatment of vitamin C but not with other antioxidants. Interestingly, the upregulation of IL17 was not accompanied by DNA demethylation in Il17 promoter and was independent of Tet enzymes. Rather, vitamin C reduced the trimethylation of histone H3 lysine 9 (H3K9me3) in the regulatory elements of the Il17 locus, and the effects of vitamin C were abrogated by knockdown of jumonji-C domain-containing protein 2 (jmjd2). These results suggest that vitamin C can affect the expression of IL17 by modulating the histone demethylase activity.

Anti-Candida Activity of YH-1715R, a New Triazole Derivative

  • Park, Kang-Sik;Kang, Heui-Il;Lee, Jong-Wook;Paik, Young-Ki
    • Journal of Microbiology and Biotechnology
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    • v.14 no.4
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    • pp.693-697
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    • 2004
  • YH-1715R, (2R,3R)-2-(2,4-difluorophenyl)-3-(3-methoxy-1,2,4-isothiazol-3-yl-thio)-1-( 1H-1,2,4-triazol-l-yl)-2-butanol, a new triazole derivative obtained by the structural modification of fluconazole, was found to exhibit potent anti-Candida activity against a wide variety of Candida albicans (C. albicans) (MIC: 0.4-12.5 mg/l). To investigate the mode of action of YH-1715R, its effect on ergosterol biosynthesis in cell-free extracts and whole cells of C. albicans was examined. The inhibitory activity of YH-1715R was approximately ten-fold higher than that of fluconazole. To determine the primary action mechanism of YH-1715R, its inhibitory activity against lanosterol $14\alpha$-demethylase (14$\alpha$-DM), a major target for azole, was measured using gas-liquid chromatography. YH-1715R and fluconazole were found to inhibit 14a-DM with an $IC_{50}$ of 0.015 $\mu$M and 0.01$8\mu$M, respectively, plus the mode of inhibition of YH-1715R and fluconozole was noncompetitive with a $K_i$ of 0.0533$\mu$M and 0.0975$\mu$M.

Influences of Clotrimazole on the Blood Cholesterol and HDL-Cholesterol level in Rats (흰쥐의 혈중 콜레스테롤 및 HDL-콜레스테롤 함량에 미치는 Clotrimazole의 영향에 관한 연구)

  • 김성오;이명렬
    • Journal of environmental and Sanitary engineering
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    • v.12 no.3
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    • pp.87-94
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    • 1997
  • Influences of clotrimazole on the blood cholesterol and HDL-cholesterol level were studied in rats. Rats were provided food and water ad libitum and clotrimazole and methylcellulose were gavaged for 6 days. Clotrimazole was suspended in 1% methylcellulose solution as and administered at concentration 20mg/Kg, 40mg/Kg, 60mg/Kg. Body weight gain and liver weight/body weight ratio, serum cholesterol level, serum HDL-cholesterol level, serum triglyceride level, the activity of cytochrome p450 and erythromycin demethylase were determined at 6th day. Clotrimazole decreased the body weight gain a little as compared with control group and did not show any influence on liver weight/body weight ratio. Clotrimazole increased the serum HDL-cholesterol and serum triglyceride level significantly. Clotrimazole increased the microsomal cytochrome P450 significantly and increased the erythromycin demethylase (cytochrome P450 IIIA) significantly too. It might be conclued that clotrimazole showed a little influence on body weight and increased the serum lipid, especially HDL-cholesterol level. It also increased microsomal cytochrome P450 IIIA significantly. It might be concluded that clotrimazole showed a corelative influence between HDL-cholesterol and cytochrome P450 IIIA. In these results clotrimazole can be used as an anti-atherosclerotic agent by increasing the HDL-cholesterol but it is necessary that cloreimazole will show any adverse or side action on body or not.

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Toxicity and Changes in Hepatic Metabolizing Enzyme System Induced by Repeated Administration of Pectenotoxin 2 Isolated from Marine Sponges (해면체에서 추출한 Pectenotoxin 2의 마우스에서의 반복적인 투여에 의한 독성 및 간대사효소계에 주는 영향)

  • Yoon, Mi-Young;Kim, Young-Chul
    • Korean Journal of Pharmacognosy
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    • v.28 no.4
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    • pp.280-285
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    • 1997
  • Pectenotoxin 2 (PTX2), isolated from marine sponges, was examined for its hepatotoxic potential using male ICR mice. PTX2 $(20\;or\;100\;{\mu}g/kg/day,\;ip)$ was administered to mice repeatedly for one or two week. Histopathological examination revealed an increase in granularity in the liver from the mice treated with PTX2. PTX2 did not alter the parameters for hepatotoxicity and nephrotoxicity such as sorbitol dehydrogenase (SDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and blood urea nitrogen (BUN). Cytochrome P-450, cytochrome $b_5$, or NADPH cytochrome c reductase was net changed by repeated administration of PTX2. Hepatic microsomal activity of p-nitroanisole O-demethylase, but not aminopyrine N-demethylase, was slightly depressed by PTX2 administerd repeatedly $(100\;{\mu}g/kg/day,\;ip)$ fur 2 weeks. The toxicity of PTX2 $(200\;{\mu}g/kg/day,\;ip)$ was determined in mice pretreated with a metabolic inducer or inhibitor such as phenobarbital, 3-methyl-cholanthrene, $CoCl_2$, or SKF 525-A. Significant alterations in lethality and hepatotoxicity of PTX2 were observed in mice pretreated with a metabolic modulator. The results suggest that liver seems to be the target organ for PTX2 toxicity and also that induction of the PTX2 toxicity may be associated with hepatic drug metabolizing activity.

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HIF-1-Dependent Induction of Jumonji Domain-Containing Protein (JMJD) 3 under Hypoxic Conditions

  • Lee, Ho-Youl;Choi, Kang;Oh, Hookeun;Park, Young-Kwon;Park, Hyunsung
    • Molecules and Cells
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    • v.37 no.1
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    • pp.43-50
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    • 2014
  • Jumonji domain-containing proteins (JMJD) catalyze the oxidative demethylation of a methylated lysine residue of histones by using $O_2$, ${\alpha}$-ketoglutarate, vitamin C, and Fe(II). Several JMJDs are induced by hypoxic stress to compensate their presumed reduction in catalytic activity under hypoxia. In this study, we showed that an H3K27me3 specific histone demethylase, JMJD3 was induced by hypoxia-inducible factor (HIF)-$1{\alpha}/{\beta}$ under hypoxia and that treatment with Clioquinol, a HIF-$1{\alpha}$ activator, increased JMJD3 expression even under normoxia. Chromatin immunoprecipitation (ChIP) analyses showed that both HIF-$1{\alpha}$ and its dimerization partner HIF-$1{\beta}$/Arnt occupied the first intron region of the mouse JMJD3 gene, whereas the HIF-$1{\alpha}/{\beta}$ heterodimer bound to the upstream region of the human JMJD3, indicating that human and mouse JMJD3 have hypoxia-responsive regulatory regions in different locations. This study shows that both mouse and human JMJD3 are induced by HIF-1.

Draft genome sequence of humic substance-degrading Pseudomonas sp. PAMC 29040 from Antarctic tundra soil (천연 복합유기화합물인 부식질을 분해하는 남극 툰드라 토양 Pseudomonas sp. PAMC 29040의 유전체 분석)

  • Kim, Dockyu;Lee, Hyoungseok
    • Korean Journal of Microbiology
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    • v.55 no.1
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    • pp.83-85
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    • 2019
  • Pseudomonas sp. PAMC 29040 was isolated from a maritime tundra soil in Antarctica for its ability to degrade lignin and subsequently confirmed to be able to depolymerize heterogeneous humic substance (HS), a main component of soil organic matter. The draft genome sequences of PAMC 29040 were analyzed to discover the putative genes for depolymerization of polymeric HS (e.g., dye-decolorizing peroxidase) and catabolic degradation of HS-derived small aromatics (e.g., vanillate O-demethylase). The information on degradative genes will be used to finally propose the HS degradation pathway(s) of soil bacteria inhabiting cold environments.

Draft genome sequence of humic substances-degrading Pseudomonas kribbensis CHA-19 from temperate forest soil (중위도 산림토양에서 분리한 부식질 분해능이 있는 Pseudomonas kribbensis CHA-19의 유전체 염기서열 초안)

  • Kim, Dockyu;Lee, Hyoungseok
    • Korean Journal of Microbiology
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    • v.55 no.2
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    • pp.177-179
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    • 2019
  • Pseudomonas kribbensis CHA-19 was isolated from a temperate forest soil (mid latitude) in New Jersey, USA, for its ability to degrade humic acids, a main component of humic substances (HS), and subsequently confirmed to be able to decolorize lignin (a surrogate for HS) and catabolize lignin-derived ferulic and vanillic acids. The draft genome sequence of CHA-19 was analyzed to discover the putative genes for depolymerization of polymeric HS (e.g., dye-decolorizing peroxidases and laccase-like multicopper oxidases) and catabolic degradation of HS-derived small aromatics (e.g., vanillate O-demethylase and biphenyl 2,3-dioxygenase). The genes for degradative activity were used to propose a HS degradation pathway of soil bacteria.

Effect of Benzoyl Peroxide on the Activity of Drug-metabolizing Enzyme System and Lipid Peroxidation in Rats (Benzoyl peroxide가 흰쥐의 지질과산화현상에 미치는 영향)

  • Lee, H.W.;Rhee, K.S.;Hong, S.U.
    • The Korean Journal of Pharmacology
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    • v.18 no.1
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    • pp.55-63
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    • 1982
  • Lipid peroxidation is the reaction of oxidative deterioration of polyunsaturated lipids and this peroxidation involves the direct reaction of oxygen and lipid to form free radical intermediates, which can lead to autocatalysis. As results of the extensive studies on the lipid peroxidation by many authors, the relationship between lipid peroxidation and the drug metabolizing system as well as the actions of free radicals on the peroxidation was reasonably well known. For a long time, the mechanism of hepatotoxicity of $CCl_4$ was not clearly understood. However, it is now quite well established that $CCl_4$ is activated in vivo to a free radical which is a highly reactive molecule. Therefore, lipid peroxidation which induces the reduction of cytochrome P-450 and aminopyrine demethylase activity is known as decisive event of $CCl_4$ hepatotoxicity. On the other hand, it was also reported that singlet molecular oxygen produces lipid peroxidation in liver microsomes. In this study the effects of benzoyl peroxide on the lipid peroxidation and drug-metabolizing enzyme were examined. Benzoyl peroxide mixed with starch and phosphates etc. is usually used as a food additive for flour bleaching and maturing purpose because of its oxidative property. Albino rats were used for the experimental animals. Benzoyl peroxide was suspended in soybean oil and sesame oil and administered intraperitoneally or orally. TBA value and aminopyrine demethylase activity were determined in liver microsomal fraction and serum. The results were summerized as following. 1) Body weights of animals administered benzoyl peroxide suspension were decreased while that of oil administered group were increased. 2) The activity of aminopyrine demethylase was generally decreased in animals administered oil suspension of benzoyl peroxide. Furthermore, the marked reduction of the enzyme activity was observed in animals administered benzoyl peroxide intraperitoneally. 3) Generally, microsomal TBA values as well as serum TBA were significantly elevated in benzoyl peroxide group in comparison with the control group. However, the more remarkable increase of serum TBA than microsomal TBA was observed in animals administered orally for 6 days. 4) Specifically, the changing pattern of TBA value was notable in serum rather than in liver microsome by intraperitoneal administration of benzoyl peroxide.

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Effect of the Combination of Ethanol with Toluene Treatment for a Short Time Period on the Toluene Metabolizing Enzyme Activity (흰쥐에 Toluene과 Alcohol의 병행투여가 Toluene 대사 효소활성에 미치는 영향)

  • 윤종국;전재현;신중규
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.25 no.6
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    • pp.976-980
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    • 1996
  • To elucidate the effect of acute ethanol pretreatment on some toluene metabolizing enzyme activities, rats were divided into 4groups: control, alcohol-treated, toluene-treated, rat's and toluene-treated rats pretreated with ethanol. The alcohol or toluene-treated rats showed the significantly increased activities of hepatic aniline hydroxylase(AH) and aminopyrine demethylase(AD) compared to the control group. And the toluene-treated rats pretreated with ethanol showed somewhat decreased tendency of these enzyme activities compared to only toluene-treated rats. Liver benzylalcohol or aldehyde dehydrogenase activities were higher in alcohol or toluene-treated rats than those of the control group. The toluene-treated rats showed the decreased tendency of benzylalcohol dehydrogenase activities by the pretreatment of alcohol. Furthermore, toluene treated-rats showed the markedly decreased activity of benzaldehyde dehydrogenase by the ethanol pretreat-ment. On the other hand, hepatic xanthine oxidase activity in toluene-treated animals pretreated with ethanol was significantly higher than those of the toluene alone-treated rats. These results indicate that the combination of ethanol with toluene treatment for a short period of time possibly results in decreased activity of some toluene metabolizing enzymes in rats.

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Effects of Baicalin on Oral Pharmacokinetics of Caffeine in Rats

  • Noh, Keumhan;Nepal, Mahesh Raj;Jeong, Ki Sun;Kim, Sun-A;Um, Yeon Ji;Seo, Chae Shin;Kang, Mi Jeong;Park, Pil-Hoon;Kang, Wonku;Jeong, Hye Gwang;Jeong, Tae Cheon
    • Biomolecules & Therapeutics
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    • v.23 no.2
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    • pp.201-206
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    • 2015
  • Scutellaria baicalensis is one of the most widely used herbal medicines in East Asia. Because baicalein and baicalin are major components of this herb, it is important to understand the effects of these compounds on drug metabolizing enzymes, such as cytochrome P450 (CYP), for evaluating herb-drug interaction. The effects of baicalin and baicalein on activities of ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), benzyloxyresorufin O-debenzylase (BROD), p-nitrophenol hydroxylase and erythromycin N-demethylase were assessed in rat liver microsomes in the present study. In addition, the pharmacokinetics of caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) in baicalin-treated rats were compared with untreated control. As results, EROD, MROD and BROD activities were inhibited by both baicalin and baicalein. However, there were no significant differences in the pharmacokinetic parameters of oral caffeine and its three metabolites between control and baicalin-treated rats. When the plasma concentration of baicalin was determined, the maximum concentration of baicalin was below the estimated $IC_{50}$ values observed in vitro. In conclusion, baicalin had no effects on the pharmacokinetics of caffeine and its metabolites in vivo, following single oral administration in rats.