• Title/Summary/Keyword: cytochrome P450s

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Expression of Recombinant Human Cytochrome P450 1A2 in Escherichia coli Bacterial Mutagenicity Tester Strain

  • Chun, Young-Jin
    • Archives of Pharmacal Research
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    • v.21 no.3
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    • pp.305-309
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    • 1998
  • Human cytochrome P450 1A2 is one of the major cytochrome P450s in human liver. It is known to be capable of activating a number of carcinogens such as arylamines and heterocyclic amines. In order to develop the new bacterial mutagenicity test system with human P450, a full length of human P450 1A2 cDNA inserted into pCW bacterial expression vector was introduced to Escherichia coli WP2 uvrA strain which is a well-known E. coli strain for bacterial reverse mutagenicity assay. Expressed human P450 1A2 showed typical P450 hemoprotein spectra. Maximum expression was achieved at 48 hrs after incubating at $30^{\circ}C$ in terrific broth containing ampicillin, IPTG and other supplements. High level expression of P450 1A2 in E. coli WP2 uvrA membranes was determined in SDS-PAGE. The well-known mutagens 2-aminoanthracene and MElQ increased the revertant colonies of E. coli WP2 uvrA expressing human P450 1A2 without an exogenous rat hepatic post-mitochondrial supernatant (S9 fraction) in a dose-dependent manner. The results show that the functional expression of human P450 in bacterial mutagenicity tester strain will provide a useful tool for studying the mechanism of the mutagenesis and carcinogenesis of new drugs and environmental chemicals.

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Comparative effects of nicotine and diazinon on larval mortality and activity of cytochrome P-450 monooxygenases in Helicoverpa assulta and Spodoptera exigua (담배나방과 파밤나방의 유충사망률과 cytochrome P-450 monooxygenases의 활성에 미치는 니코틴과 다이아지논의 영향)

  • 이정호;부경생
    • Korean journal of applied entomology
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    • v.32 no.2
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    • pp.225-235
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    • 1993
  • This study was carried out to investigate effects of diazinon, an organophosphate, and nicotine, a plant~originated toxic chemical, on larval mortality and activity of cytochrome P-45D monooxygenases, a major detoxifwation enzyme system, in Helicoverpa assulta and Spodoptera exigua. Diazinon treatment gave a higher mortaliLy to H. assulta larvae than S. exigua larvae. In contrast to the case of diazinon, nicotine caused a higher mortahty to S. exigua than to H. assulla larvae. It was partly due to the fact that nicotine induced the actiVIty of midgut cytochrome P-450 monooxygenases (MFO) more than diazinon did in If assulta larvae. When If. aSSlllta larvae were reared on their host p\am. NicotwlIa tuoocum leaves, other componentS were mostly metabolized with the exception of dietary nicotine.

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Effects of $\Upsilon$-Irradiated Pork Feeding on Preneoplastic Hepatic Lesion, Cytochrome P450 System and Microsome Glucose 6-Phosphatase Activity in Rat Hepatocarcinogenesis (실험적 간 발암모델에서 감마선 조사 돼지고기 섭취가 전암성병변의 생성, 약물대사 효소계 및 소포체 막 안정성에 미치는 영향)

  • 김미정;김정희
    • Journal of Nutrition and Health
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    • v.35 no.6
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    • pp.643-649
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    • 2002
  • This study was done to investigate effects of ${\gamma}$-irradiated pork feeding on the formation of glutathione S-transferase placental form positive (GST-P$^{+}$) foci, lipid peroxidation, cytochrome P450 system and microsomal glucose 6-phosphatase activity in diethylnitrosamine (DEN)-initiated rat hepatocarcinogenesis. Weaning Sprague-Dawley male rats were fed the diet containing ${\gamma}$-irradiated ground pork at the dose of 0, 3, 10, 30 kGy as a 20% of protein source for 8 weeks. One week after feeding, rats were intraperitoneally injected twice with a dose of DEN (50 mg/kg BW). As a promote.,0.05%phenobarbital was fed in drinking water from one week after DEN treatment until the end of experiment. At the end of 8th week, rats were sacrificed and hepatic GST-P$^{+}$ foci, microsomal malondialdehyde (MDA) and conjugated diene contents were determined. In addition, cytochrome P450 content and the activities of NADPH cytochrome P450 reductase and glucose 6-phosphatase were also measured. There was no significant effect by gamma irradiation on microsomal MDA content, conjugated diene, cytochrome P450 content and activities of NADPH cytochrome P450 reductase and glucose 6-phosphatase. However with DEN treatment, microsomal MDA content showed a increasing tendency. Cytochrome P450 content was also significantly increased while microsomal glucose 6-phophatase activity was significantly decreased with DEN treatment. However the activity of NADPH cytochrome P450 reductase was not affected. An interesting finding in this study was that the number and area of hepatic GST-P$^{+}$ foci of rats fed gamma irradiated pork were tended to be decreased by high dose of irradiation, but were not significantly different. These results might imply that the consumption of low dose of gamma irradiated pork does not affect the formation of hepatic GST-P$^{+}$ foci and lipid peroxide and membrane stability.ability.

Proposed Mechanisms and Further study for Korean Traditional medicines-Drug Interaction in a view of Toxicology (한약의 약물상호작용 기전과 연구방향 - 독성학적인 측면을 중심으로 -)

  • Park, Yeong-Chul;Kim, Myung-Dong;Lee, Sun-Dong
    • Journal of Society of Preventive Korean Medicine
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    • v.15 no.1
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    • pp.1-16
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    • 2011
  • Objectives : The mechanisms for korean traditional medicine-drug interaction has not been well reviewed in spite that the chance for co-administration with western drugs or diet supplements has been increased. Especially, it is well known that various cytochrome P450s play a major role in drug-drug interaction. Of course, Korean traditional medicines is not excluded in a view of metabolism or biotransformation by cytochrome P450. This article was focused on reviewing the possible roles of cytochrome P450 in Korean traditional medicine-drug interaction, Also, the directions for further studies were suggested in terms of Korean traditional medicine-drug interaction. Methods : New studies for korean traditional medicine-drug interaction were reviewed and summarized in terms of cytochrome P450 activities by various Korean traditional medicines and western drugs. Results and Conclusions : Even if a few studies related to Korean traditional medicine-drug interactions was carried out, almost no studies for Korean traditional medicine-drug interactions has been found in a view of cytochrome P450. It was suggested that Korean traditional medicines and their decoction should be analyzed that how they effects on cytochrome P450, expecially CYP 1, 2, 3 families and how they interact with western drugs.

Activity of Mixed Function Oxidase in a few Insect Species in Relation to Their Food Source (먹이종류에 따른 몇가지 곤충의 MFO활성 비교)

  • 이정호;부경생
    • Korean journal of applied entomology
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    • v.32 no.3
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    • pp.291-299
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    • 1993
  • Midgut tissues from 4 insect specIes were exammed for the activity of cytochrome P-450 monooxygenases, a major enzyme involved in chemical detoxification. When Helicoverpa assulta larvae were reared on an artificial d;et, the specific activity of the midgut cytochrome P-450 monooxygenases (MFO) was :3 times higher than that of the fat body, The specific activity of the midgut cytochrome P-450 monooxygenases was higher in H. assul/a larvae when reared on Nicotiana tabacum leaves than when on CapsIcum annuum fruits or an artificial diet. In the case of Hyphantria cunea larvae, Tilia megaphyllo leaves were the best in inducing midgut cytochrome P-450 monooxygenases activity. When larvae of H. assulta, Spodoptera exigua, H. cunea and Spodoptera litura were reared on their own artificial diet, the highest activity was seen in S. exigua larvae which is a polyphagous and insecticide-resistant strain.

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Induction of Phase II Enzymes and Inhibition of Cytochrome P450 Isozymes by Chitosanoligosaccharides

  • SHON, YUN-HEE;NAM, KYUNG-SOO
    • Journal of Microbiology and Biotechnology
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    • v.15 no.1
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    • pp.183-187
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    • 2005
  • Abstract The cancer chemopreventive potential of chitosanoligosaccharides was investigated by measuring the induction of quinone reductase and glutathione S-transferase activities and inhibition of cytochrome P450 1A1, 2B1, and 2E1 activities. Chitosanoligosaccharide I (1-${\kappa}$Da${\kappa}$Da) significantly induced glutathione S-transferase activity with a maximal 1.5-fold increase at 500 ${\mu}$g/ml, while chitosanoligosaccharide II (3-${\kappa}$Da${\kappa}$Da) (500 ${\mu}$g/ml) strongly induced quinone reductase (p<0.01) and glutathione S-transferase (p<0.005) activities. The in vitro incubation of rat liver microsomes with chitosanoligosaccharides I and II (2.5, 5, 50, and 500 ${\mu}$g/ml) showed a dose-dependent inhibiton of cytochrome P450 1A1, 2B1, and 2E1 activities. Chitosanoligosaccharide II was a more potent inhibitor of cytochrome P450 2B1 activity than chitosanoligosaccharide I. Accordingly, these findings suggest that chitosanoligosaccharides are potential chemopreventive agents.

Cancer Activation and Polymorphisms of Human Cytochrome P450 1B1

  • Chun, Young-Jin;Kim, Donghak
    • Toxicological Research
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    • v.32 no.2
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    • pp.89-93
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    • 2016
  • Human cytochrome P450 enzymes (P450s, CYPs) are major oxidative catalysts that metabolize various xenobiotic and endogenous compounds. Many carcinogens induce cancer only after metabolic activation and P450 enzymes play an important role in this phenomenon. P450 1B1 mediates bioactivation of many procarcinogenic chemicals and carcinogenic estrogen. It catalyzes the oxidation reaction of polycyclic aromatic carbons, heterocyclic and aromatic amines, and the 4-hydroxylation reaction of $17{\beta}$-estradiol. Enhanced expression of P450 1B1 promotes cancer cell proliferation and metastasis. There are at least 25 polymorphic variants of P450 1B1 and some of these have been reported to be associated with eye diseases. In addition, P450 1B1 polymorphisms can greatly affect the metabolic activation of many procarcinogenic compounds. It is necessary to understand the relationship between metabolic activation of such substances and P450 1B1 polymorphisms in order to develop rational strategies for the prevention of its toxic effect on human health.

Theoretical Study on The Interaction Between Benzo(a)pyrene and Cytochrome P-450 (Benzo(a)pyrene 과 Cytochrome P-450의 대한 상호작용에 대한 이론적 연구)

  • 도성탁
    • Biomedical Science Letters
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    • v.1 no.1
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    • pp.89-94
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    • 1995
  • Considering the planar structure and nonpolar properity of benzo(a)pyrene(B(a)p) and the planar heme part of cytochrome P-450, stacking interaction is probable. MO calculation on B(a)P and heme part of cytochrome P-450 were carried out to dertermine probable stacking interaction models. In this case, orbital interaction is most important. Accordingly, the stacking positions have high eigen vector in frontier orbital and boning type between two molecules. In this way, five probate models were selected and examined by MN2 and MO method. The most probable .stacking interaction model which is the 4, 5, 6 positions of B(a)P overlap carbon atom and pyrrole ring of ring of heme group was determined.

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Inhibitory effect of honokiol and magnolol on cytochrome P450 enzyme activities in human liver microsomes

  • Joo, Jeongmin;Liu, Kwang-Hyeon
    • Mass Spectrometry Letters
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    • v.4 no.2
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    • pp.34-37
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    • 2013
  • Honokiol and magnolol, the major bioactive neolignans of magnolia officinalis, are the most important constituents of the crude drug prescriptions that are used in the therapy of neuroses and various nervous disorders. There have been limited reports on the effects of neolignoid compounds on human cytochrome P450 activity. Therefore, the inhibitory effects of honokiol and magnolol on seven human cytochrome P450 s were evaluated in human liver microsomes. Honokiol and magnolol showed the most potent inhibition of CYP1A2-mediated phenacetin O-deethylase activity ($IC_{50}$ values of 3.5 and 5.4 mM, respectively) among the seven P450s tested. These in vitro data indicate that neolignan compounds can inhibit the activity of CYP1A2 and suggest that these compounds should be examined for potential pharmacokinetic drug interactions in vivo.

Effects of($\pm$)-camphor on Hepatic Cytochrome P450 Enzymes in Male ICR Mice (($\pm$)-Camphor가 ICR 마우스 수컷의 간 cytochrome P450 효소 활성에 미치는 영향)

  • 오은경;박형건;배기헌;최옥진;최은경;최창근;한진희;정태천
    • Environmental Analysis Health and Toxicology
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    • v.17 no.4
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    • pp.307-314
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    • 2002
  • Effects of ($\pm$)-camphor on liver cytochrome P450 enzymes were investigated in male ICR mice. Mice were treated intraperitoneally with 0, 200, 400 and 800 mg/kg of ($\pm$)-camphor in corn oil for 3 consecutive days. Twenty four hr after the final treatment, the animals were subjected to necropsy. The activities of serum aspartate aminotransferase and serum alanine aminotransferase were slightly changed by the treatment with ($\pm$)-camphor at the doses used. Administration of ($\pm$)-camphor to mice significantly induced the hepatic activities of pentoxyresorufin O-depentylase and benzyloxyresorufin O-debenzylase and weakly induced ethoxyresorufin O-deethylase in dose-dependent manners. The present results suggested that ($\pm$)-camphor might act as a relatively specific inducer of hepatic cytochrome P450 2B in male ICR mice.