• Title/Summary/Keyword: Cytochrome P450 monooxygenase

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Modulation of Cytochrome P-450 Induction by Long-Term Supplementation with Korean Red Ginseng to Rats (홍삼의 장기 투여가 흰쥐 간 대사효소 유도에 미치는 영향)

  • Lim, Heung-Bin
    • Korean Journal of Medicinal Crop Science
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    • v.15 no.6
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    • pp.437-443
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    • 2007
  • This study was carried out to investigate the effect of dietary supplementation with red ginseng water-extracts on the induction of microsomal cytochrome P-450 in rats. Phenobarbital (PB) and 3-methylcholanthrene (3-MC), P-450 inducers, were administered to 3- or 12-month old rats received red ginseng extracts (25 mg/kg) from 6 weeks to 12 months for 3 days. PB and 3-MC increased levels of P-450, P-450 reductase, ethoxycoumarin O-deethylase, benzphetamine N-demethylase and glutathione-S-transferase in the liver of rats. However, chronic administration of red ginseng significantly reduced these increase of enzyme levels induced by P-450 inducers. Chronic administration of red ginseng did not affect the induction of cytochrome $b_5$ and NADH cytochrome $b_5$ reductase by P-450 inducers. It is suggested that the induction of cytochrome P-450 system in the liver in relation to xenobiotics toxicity can be modulated by long-term supplementation with Korean red ginseng to rats.

Effect of Insecticide Carbofuran and Phenobarbital Sodium and 3-Methylcholanthrene on Activity of Enzyme in Israeli Carp(Cyprinus israeli carpio L.) (살충제 Carbofuran과 Phenobarbital Sodium 및 3-Methylcholanthrene이 이스라엘 잉어의 효소활성에 미치는 영향)

  • Rim, Yo-Sup;Jeong, Jae-Hun;Han, Seong-Soo
    • Applied Biological Chemistry
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    • v.39 no.1
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    • pp.77-83
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    • 1996
  • Effects of insecticide carbofuran and Phenobarbital sodium(PB) or 3-methylcholanthrene(3-MC) on activities of several enzymes in israeli carps were investigated. Survival number of Israeli carp was the same as that of control when PB and 3-MC only was treated, individually and that was low compared to control when carbofuran only was treated. But survival rate of Israeli carp was high compared to individual treatment of carbofuran when combination treatment of carbofuran and PB or 3-MC was carried out. These results indicate that PB and 3-MC can intervene to detoxify carbofuran exposed to israeli carp. In in vivo test for the effect of this chemicals on activity of enzyme in israeli carp, activities of acetylcholinesterase(AChE) and glutathione S-transferase(GST) were inhibited in carbofuran treatment, but did not in combination treatment of carbofuran and P3 or 3-MC. Activities of UDP-glucuronosyltransfe-rase (UDPGT) and cytochrome P-450-dependent monooxygenase increased in individual or combined treatments of carbofuran and PB or 3-MC. These results suggest that a simultaneous application of carbofuran and PB or 3-MC is critical for the enhancement of activity of AChE, GST, UDPGT and monooxygenase and the protection of Israeli carp from carbofuran toxicity.

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Cross Resistance and Point Mutation of the Mitochondrial Cytochrome b of Bifenazate Resistant Two-spotted Spider Mite, Tetranychus urticae (Bifenazate 저항성 점박이응애에 대한 교차저항성과 미토콘드리아 cytochrome b의 점돌연변이)

  • Lee, Kyo-Ri;Koo, Hyun-Na;Yoon, Chang-Mann;Kim, Gil-Hah
    • The Korean Journal of Pesticide Science
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    • v.14 no.3
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    • pp.247-254
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    • 2010
  • Two-spotted spider mite, Tetranychus urticae was collected from the rose greenhouse in Chilgok, Gyeongbuk Province in December 2000. This population has been selected for ten years with bifenazate (over 450 times), and increased 855.9 fold in resistance as compared with susceptible strain (S). Cross resistance of bifenazate resistant (BR) strain to eight miticides was investigated. The BR strain exhibited high and low cross resistance to acequinocyl (614.0 fold) and to chlorfenapyr (9.1 fold), respectively. Against fenazaquin (0.3 fold) and fenpyroximate (0.1 fold), however, showed the strain negatively correlated cross resistance. Each strain collected in Choeng-ju (CJ), Kang-jin (KJ), and Chung-ju (CUJ) showed 5.5-, 964.5-, and 21.8-fold resistance to bifenazate, respectively. The detoxifying enzymes of the BR strain showed 1.6-fold activity in cytochrome $P_{450}$-dependent monooxygenase ($P_{450}$) as compared with susceptible one. By comparing the mitochondrial cytochrome b (cytb) sequence, G126S point mutation was detected in the BR and KJ strains.

Effect of Trichloroethylene on the Induction of Rat Liver Microsomal Enzymes

  • Chang, Sung-Keun;Jeong, Hyo-Seok;Chai, Se-Ok;Kim, Ki-Woong;Park, Sang-Shin
    • BMB Reports
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    • v.30 no.4
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    • pp.237-239
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    • 1997
  • The effects of trichloroethylene (TRI) on the induction of cytochrome P-450 (CYP) and several other related enzymes in Sprague Dawley rats were investigated Rats were treated with TRI 150. 300. 600 mg/kg body weight in corn oil intra peritoneally once a day for 2 days. The total contents of microsomal CYP and cytochrome $b_5\;(b_5)$ decreased with the increase of TRI concentration. but the activity of p-nitrophenol hydroxylase increased with the increase of TRI dosage (p<0.05). Western blot analysis which utilized monoclonal antibodies against CYP2E1 also showed a significant increase in the CYP2E band density. The increase of the activity of pentoxyresolufin-O-deethylase also was observed with the TRI treatment (p<0.05) although there was no significant increase in the cytochrome CYP2B1/2 in Western blotting The TRI did not affect the induction of aryl hydrocarbon hydroxylase. These findings suggest that the CYP2E1 is the primary enzyme which could be induced by TRI treatment in rats.

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ROLE OF METABOLISM BY FLAVIN-CONTAINING MONOOXYGENASE IN THIOACETAMIDE-INDUCED IMMUNOSUPPRESSION

  • Woo S. Koh;Lee, Jeong W.;Tae C. Jeong
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.05a
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    • pp.73-73
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    • 2002
  • Thioacetamide has been known to cause immune suppression. The object of the present study is to investigate the role of metabolic activation by flavin- containing monooxygenases (FMO) in thioacetamide-induced immune response. To determine whether the metabolites of thioacetamide produced by FMO causes the immunosuppression, methimazole (MMI), an FMO inhibitor, was used to block the FMO pathway.(omitted)

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Enzymatic Study on Acetanilide p-Hydroxylase in Streptomyces fradiae

  • Jin, Hyung-Jong;Park, Ae-Kyung;Lee, Sang-Sup
    • Archives of Pharmacal Research
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    • v.15 no.3
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    • pp.215-219
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    • 1992
  • S. fradiae exhibited the highest acetanilide p-hydroxylation activity among the Streptomyces spp. screened. Studies with inhibitors (metyrapone, 2. 6-dichloroindophenol, $\alpha,\alpha'$-dipyridyl, o-phenanthroline) and an absorption peak after CO treatment suggested that S. fradiae hydroxylase activity was due to cytochrome p-450. This hydroxylase activity was increased to ten times in the cell extract containing 0.5 mM sodium azide. Furthermore, the sedimentary activity in $105,000\times{g}$ centrifugal forces and solubilization of the activity with Triton-X 100 implied that this enzyme was membrane bound monooxygenase. pH Optimum of the enzyme was 6.5 in membrane bound state.

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Homology Modeling and Molecular Docking Analysis of Streptomyces peucetius CYP125A4 as C26 Monooxygenase

  • Lee, Seung-Won;Lee, Na-Rae;Lee, Ji-Hun;Oh, Tae-Jin
    • Bulletin of the Korean Chemical Society
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    • v.33 no.6
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    • pp.1885-1889
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    • 2012
  • Among 23 cytochrome P450s, CYP125A4 was proposed as a putative monooxygenase based on the high level of amino acid sequence homology (54% identity and 75% similarity) with the well characterized C27-steroid $Mycobacterium$ $tuberculosis$ CYP125A1. Utilizing MTBCYP125A1 as a template, homology modeling of SPCYP125A4 was conducted by Accelrys Discovery Studio 3.1 software. The modeled SPCYP125A4 structure with lowest energy value was subsequently assessed for its stereochemical quality and side-chain environment. The final model was generated by showing its active site through the molecular dynamics. The docking of steroids showed broad specificity of SPCYP125A4 with different orientation of ligand within active site facing the heme. One poses of C27-steroid with C26 facing the heme with distance of 3.734 ${\AA}$ from the Fe were predominant.

Self-Sufficient Catalytic System of Human Cytochrome P450 4A11 and NADPH-P450 Reductase

  • Han, Song-Hee;Eun, Chang-Yong;Han, Jung-Soo;Chun, Young-Jin;Kim, Dong-Hyun;Yun, Chul-Ho;Kim, Dong-Hak
    • Biomolecules & Therapeutics
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    • v.17 no.2
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    • pp.156-161
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    • 2009
  • The human cytochrome P450 4A11 is the major monooxygenase to oxidize the fatty acids and arachidonic acid. The production of 20-hydroxyeicosatetraenoic acid by P450 4A11 has been implicated in the regulation of vascular tone and blood pressure. Oxidation reaction by P450 4A11 requires its reduction partners, NADPH-P450 reductase (NPR). We report the functional expression in Escherichia coli of bicistronic constructs consisting of P450 4A11 encoded by the first cistron and the electron donor protein, NPR by the second. Typical P450 expression levels of wild type and several N-terminal modified mutants was observed in culture media and prepared membrane fractions. The expression of functional NPR in the constructed P450 4A11: NPR bicistronic system was clearly verified by reduction of nitroblue tetrazolium. Membrane preparation containing P450 4A11 and NPR efficiently oxidized lauric acid mainly to $\omega$-hydroxylauric acid. Bicistronic coexpression of P450 4A11 and NPR in E. coli cells can be extended toward identification of novel drug metabolites or therapeutic agents involved in P450 4A11 dependent signal pathways.

Effects of Polycyclic Aromatic Hydrocarbons on Liver and Lung Cytochrome P450s in Mice

  • Kim, Ji-Young;Lee, Sang-Kyu;Kim, Chun-Hwa;Jeon, Tae-Won;Moon, Chang-Kiu;Lee, Hye-Sook;Yoo, Sun-Dong;Lee, Eung-Seok;Jeong, Tae-Cheon
    • Archives of Pharmacal Research
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    • v.26 no.5
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    • pp.394-404
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    • 2003
  • Certain polycyclic aromatic hydrocarbons (PAHs) have been reported to induce cytochrome P450 (CYP) 1A1 and 1A2. In the present study, the effects of six well-known PAHs, such as benzo[a]pyrene, benz[a]anthracene, dibenz[a,h]anthracene, chrysene, benzo[k]fluorancene and benzo[b]fluorancene, on the activities of hepatic and pulmonary CYP enzymes were investigated in male ICR mice. When mice were treated intraperitoneally with 3, 10 and 30 mg/kg of individual PAHs for 3 consecutive days, the activities of ethoxyresorufin- and methoxyresorufin-Ο-dealkylases were significantly and differentially induced in both liver and lung. Moreover, other CYP isozyme-associated monooxygenase activities were also induced significantly in liver and lung with characteristic induction profiles. Our present results suggest that individual PAHs might have inductive effects on CYP isozymes, and that the characteristic inductive effects of individual PAHs on certain CYP isozymes would be developed as a marker for determining exposure to certain PAHs.