• Title/Summary/Keyword: Cytochrome P450

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Effect of Dietary Vitamin E on the Microsomal Mixed Function Oxidase System of Liver and Lung in Streptozotocin-induced Diabetic Rats (식이 Vitamin E가 Streptozotocin 유발 당뇨쥐의 간 및 폐조직에서의 Microsomal Mixed Function Oxidase System에 미치는 영향)

  • 박영란;이순재;임영숙;주길재
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.25 no.6
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    • pp.969-975
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    • 1996
  • The purpose of this study was to investigate the effect of dietary vitamin E on microsomal mixed function oxidase system of liver and lung in streptozotocin(STZ) induced diabetic rats. Sprague-Dawley male rats weighing 140 $\pm$ 10mg were randomly assigned to one control and three STZ-diabetic groups. Diabetic groups were divided into DM-0E(vitamin E free diet), DM-40E(40mg vitamin E kg/diet) and DM-400E(400mg vitamin E kg/diet) according to the level of vitamin E supplementation. Diabetes was experimentally induced by intravenous administration of 55mg/kg b.w of STZ in citrate buffer(pH 4.3) after 4 week feeding of three experimental diets. Animals were sacrificed at the 6th day of diabetic state. The contents of cytochrome P$_{450}$ in DM-0E, DM-40E and DM-400E groups of liver were increased by 162%, 150% and 56%, respectively, compared with that of control. Also the contents of cytochrome P$_{450}$ in lung were similar to liver. The activities of cytochrome bs in DM-0E and DM-40E groups of the liver were increased by 70% and 53%, respectively, compared with that of control, but not in DM-400E group. The activities of bs in DM-0E, DM-40E and DM-400E groups of lung were signficantly increased. Activity of cytochrome P$_{450}$ reductase in DM-0E, DM-40E of liver and lung were higher than that of control group, but the activity of DM-400E group was not different from that of control. The lipid peroxide values of DM-0E, DM-40E and DM-400E groups were 143%, 95% and 31% higher than those of control. It was concluded that dietary vitamin E had protective effects on lipid peroxidation accompanied with increased mixed function of oxidase activity in diabetic rats.

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Correlation between microsomal lipid peroxidation levels and drug metabolizing enzymes in rats on various ages (연령증가에 따른 마이크로솜 막지질 과산화수준의 변화와 해독효소계의 관계)

  • Cho, Jong-Hoo;Hwang, DaeWoo;Park, Sang-Youel
    • Korean Journal of Veterinary Research
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    • v.43 no.4
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    • pp.579-585
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    • 2003
  • The studies were carried out on the correlation between microsomal lipid peroxidation level and drug metabolizing enzyme activities in rat liver microsomal suspensions on various ages (2-week-old, 2, 4, 8, and 12-month-old). The lipid peroxidation levels of liver homogenates tended to be elevated in a 4-month-old rat livers, but it was a little decreased in 8 and 12-month-old rat livers. The lipid peroxidation levels of microsomal suspension was not shown any significant differences by ages. Lipid peroxidation levels and microsomal cytochrome P450 and NADPH-cytochrome c reductase activity showed a direct correlation (r=0.72 and r=0.64), respectively. The activities of cytochrome P450-dependent aminopyrine-N-demethylase and benzpyrene hydroxylase in rat liver microsomes were increased by ages up to 8-month-old rats and maintained in 12-month-old rats. The correlation between lipid peroxidation levels and these cytochrome-dependent enzyme activities showed a high direct correlation (r=0.97 and r=0.81), respectively.

Sex- and Tissue-related Expression of Two Types of P450 Aromatase mRNA in the Protandrous Black Porgy, Acanthopagrus schlegeli, during Sex Reversal: Expression Profiles Following Exogenous Hormone Administration

  • Min, Tae-Sun;An, Kwang-Wook;Kil, Gyung-Suk;Choi, Cheol-Young
    • Animal cells and systems
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    • v.13 no.4
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    • pp.439-445
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    • 2009
  • Cytochrome P450 aromatase (P450arom) catalyzes the conversion of androgens to estrogens and plays an important role in reproduction and development in vertebrates. We investigated the expression patterns of ovarian P450arom (P450aromA) and brain P450arom (P450aromB) mRNA during sex change in black porgy. Maturity was divided into seven stages from male to female (immature testis, mature testis, testicular portion of mostly testis, ovarian portion of mostly testis, testicular portion of mostly ovary, ovarian portion of mostly ovary, and mature ovary). P450aromA expression was significantly higher in the ovarian portion of mostly-ovarian stage fish, and P450aromB expression was highest in the brain of black porgy with mostly-ovarian gonads. Histology showed that testicular tissues were disintegrated with the development of ovarian tissue associated with an increase in the expression of the two P450arom mRNAs during sex change. Interestingly, among various tissues, P450aromA was only expressed in the ovary, and P450aromB was only expressed in the brain. To understand the role of gonadotropin-releasing hormone (GnRH) and estradiol ($E_2$), we injected exogenous hormone (GnRH analogue [GnRHa] and $E_2$) into immature black porgy. In the GnRHa group, expression of the two P450arom genes decreased 12 h after injection, and expression of the two P450arom genes were significantly higher at 6 dafter $E_2$ injection. These results provide useful baseline knowledge on the mechanism of natural sex change in black porgy.

A Study of Tissue-Specific Expression and Analysis of Structure and DNA Sequences of Porcine Cytochrome P450 Aromatase Genes

  • Ghimeray, Amal-Kumar;Chae, Sung-Hwa;Lee, Eun-Ju;Quan Feng;Nina Oriero;Park, Inho
    • Proceedings of the KSAR Conference
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    • 2004.06a
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    • pp.196-196
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    • 2004
  • By use of RT-PCR coupled with DHPLC technique (WAVE analysis), pattern of isoforms of porcine cytochrome P450 aromatase gene was investigated. Relatively higher expression of aromatase mRNA was observed in testis than in ovary and this result accounted for the previous findings of higher blood estrogen level in male compared with female in this species. (omitted)

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Role of Metabolic Activation by Cytochrome P450s in Chemical- induced Immunosuppression

  • Jeong, Tae-Cheon;Lee, Eung-Seok;Chae, Whi-Gun
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.201-205
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    • 2002
  • It is generally accepted that the immune system is one of the major target organs for many toxic chemicals. In addition, many toxic chemicals require metabolic activation by cytochrome P450s for their toxicity. Although the immune cells possess a limited amount of drug metabolizing capacity, metabolic activation of certain toxicants in liver and immune organs may have a significant role in immunosuppression. In the present studies, the possible role of metabolic activation by cytochrome P450s in chemical-induced immunosuppression was reviewed, with a particular emphasis on the methodological techniques to detect immunotoxicants requiring metabolic activation in vivo and in vitro. (omitted)

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Hepatic Response in Cytochrome P45O and De-alkylase Activity of Olive Flounder (Paralichthys olivaceus) Exposed to Water-borne Phenanthrene

  • Jee, Jung-Hoon;Park, Dae-Kuk;Kang, Ju-Chan
    • Journal of Aquaculture
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    • v.16 no.2
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    • pp.99-103
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    • 2003
  • Olive flounder (Paralichthys olivaceus) was exposed to water-borne phenanthrene for 4 weeks. After the exposure for 2-weeks, hepatic cytochrome P450 contents were significantly elevated. Induction of hepatic ethoxy resorufin-O-deethylase (PROD) activity was significantly increased in flounders treated with 1.0 and 2.0 $\mu$M phenanthrene, compared to untreated group and 0.5 $\mu$M treated group. However, there were no significant changes in pentoxyresorufin-O-deethylase (PROD) activity in hepatic microsome of all the phenanthrene-treated groups, compared to the untreated group. Phenanthrene has the potential to induce cytochrome P450 and EROD enzyme of the olive flounder.

Mixed-type Inhibition of Human Hepatic Cytochrome P450 1-Catalyzed Ethoxyresorufin O-deethylation by Volatile Allyl Sulfides

  • Kim, Hyun-Jung;Chun, Hyang-Sook
    • Food Science and Biotechnology
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    • v.14 no.2
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    • pp.297-300
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    • 2005
  • Effects of allyl sulfides on kinetic behavior of cytochrome P450 1 (CYP1)-catalyzed ethoxyresorufin O-deethylase (EROD) activity were studied using microsomes from benzo[a]pyrene-treated human hepatoma cells. Apparent $K_m$ and $V_{max}$ values were calculated as $2.8\;{\mu}M$ and $3.0\;{\mu}mol$ resorufin/min/mg protein based on Lineweaver-Burk plot of microsomal EROD activity, respectively. Diallyl disulfide (DADS) and diallyl trisulfide (DATS) affected $K_m$ and $V_{max}$ values of EROD activity and acted as mixed-type inhibitors for CYP1 isozymes. Apparent Ki values of DADS and DATS were calculated as 1.07 and 0.88 mM, respectively, by re-plotting slopes of Lineweaver-Burk plot and inhibitor concentrations.

Modulation of human cytochrome P450 1B1 by 2,3',4,5'-tetramethoxystilbene(TMS) in mammary tumor cells and its application for cancer chemotherapy

  • Lee, Sang-Kwang;Kim, Sanghee;Kim, Mie-Young;Chun, Young-Jin
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2003.05a
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    • pp.77-77
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    • 2003
  • We have previously shown that 2, 3' , 4, 5' -tetramethoxystilbene(TMS), a trans-stilbene analogue, is one of the most potently selective inhibitor of recombinant human cytochrome P450 1B1 in vitro. In the present studies, the effects of TMS on the expression of cytochrome P450 1B1 were investigated in human mammary cell lines such as MCF-7 and MCF-10A. (omitted)

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Isolation of Human CYP4F2 genomic DNA and its $5^I$ End Regulatory Region Structure

  • Jin, Hyung-Jong
    • Archives of Pharmacal Research
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    • v.21 no.1
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    • pp.35-40
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    • 1998
  • Human cytochrome P450 4F2 shows high regioselectivity in hydroxylation of stearic acid and leukotriene $ B_4.$ As a first step of its regulation study, human cytochrome P450 4F2 genomic DNA was isolated from liver of a person who was administered clofibrate for 10 years. From Southern hybridization, restriction enzyme digestion and sequencing experiments, isolated genomic DNA fragment was found to contain around 32 Kb DNA and more than 20 Kb of $5^I$ end regulatory region. Sequences of the structural gene region revealed exon 1 and exon 2. Further regulation studies would elucidate the feedback mechanisms of the oxidative degradation of fatty acids, inflammatory response and the clearance of leukotriene B4 in the liver. Furthermore, regulation study of this gene could explain the species difference in responses to peroxisome proliferator and help in the safety evaluation of peroxisome proliferating chemicals to human being.

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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.