• Title/Summary/Keyword: cytochrome p-450

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ROLE OF 5'FLANKING DNA FOR THE REGULATION OF CYP450IA1 GENE EXPRESSION

  • Sheen, Yhun-Y.
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1995.10a
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    • pp.153-155
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    • 1995
  • To investigate the mechanism of the regulation of cytochrome P450IAl, the 5'-flanking region of a trout cytochrome P4501Al was cloned into the CAT basic expression vector at HindⅢ site. This trout Cytochrome P450IAl upstream DNA containing CAT construct was transfected into Hepa-1 cells .3MC treatment to hepa I cells transfected with trout P450IAl-CAT construct increased CAT protein and mRNA by 2.81 fold when it was compared with that of control. This increase CAT protein and mRNA was decreased by concomitantly treated flavonoids and aminopyrine. The level of CAT protein was 29.2-58.0% of 3MC stimulated CAT protein.

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Modulation of Cytochrome P450 1B1 Expression by A Stilbene Analog and its Effect on the Sensitivity to Anticancer Agents in Human Cancer Cells.

  • Lee, Sang-Kwang;Park, Sung-Sik;Kim, Mie-Young;Chun, Young-Jin
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.209.1-209.1
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    • 2003
  • We have previously shown that 2, 3', 4, 5' -tetramethoxystilbene(TMS) from synthetic trans-stilbene analogues, 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 cancer cell lines such as MCF-7 and HL -60. TCDD-stimulated P450 1B1 protein and mRNA expression was significantly suppressed by TMS in a dose-dependent manner. (omitted)

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독성물질 대사효소 조절기전에 관한 연구

  • 윤여표;홍연탁;김부영
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1992.05a
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    • pp.54-54
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    • 1992
  • 약물, hormone, 독성물질등의 대사능과 발암 가능성등이 간장 장해시 및 ketosis시에 달라지는 원인과 기전, 독성물질 대사효소의 변동과 그 작용기전을 규명하고자, 대표적인 간장장해 물질인 carbon tetrachloride를 rat에 투여하여 간장 장해를 일으키고, 당뇨병, starvation, high-fat diet처리하여 ketosls상태를 만든 후에, specific cytochrome P45O polyclonal antibodies와 cDNA probes를 사용하여, enzyme activitieg, Western immunoblot analysis와 mRNA Northern blot analysis 등을 실험하여, 간장 장해와 ketosis시 cytochrome P45O의 변동과 그 작용기전, regulation을 규명하고자 하였다. 실험 결과, $CCl_4$투여후 P450IIE enzyme (aniline hydroxylase) 활성이 시간 의존적으로 급격히 떨어졌고, P450IIE protein양이 똑같은 방식으로 감소되었으나 mRNA level은 변화가 없었다. $CCl_4$에 의해서 P450IIE는 protein의 특이적인 파괴에 의한 post-translational reduction됨을 알 수 있었다. 반면에 당뇨병, starvation, high-fat diet등 ketosis시에는 P450IIE 효소활성이 2-3배 증가되었고, P450IIE protein양도 같은 수준으로 증가되었으며, mRNA도 증가 되었다. Ketosis시에는 P450IIE가 pretranslational activation됨을 알 수 있었다.

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Overexpression of rice premnaspirodiene oxygenase reduces the infection rate of Xanthomonas oryzae pv. oryzae

  • Nino, Marjohn C.;Song, Jae-Young;Nogoy, Franz Marielle;Kim, Me-Sun;Jung, Yu Jin;Kang, Kwon-Kyoo;Nou, Illsup;Cho, Yong-Gu
    • Journal of Plant Biotechnology
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    • v.43 no.4
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    • pp.422-431
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    • 2016
  • Plants utilize cytochrome P450, a large superfamily of heme-containing mono-oxygenases, in the synthesis of lignins, UV protectants, pigments, defense compounds, fatty acids, hormones, and signaling molecules. Despite the overwhelming assortment of rice P450 accession numbers in the database, their functional studies are lacking. So far, there is no evidence involving rice P450 in disease immunity. Most of our understanding has been based on other plant systems that are mostly dicot. In this study, we isolated the cytochrome P450 (OsCYP71) in rice, and screened the gene using gain-of-function technique. The full-length cDNA of OsCYP71 was constitutively overexpressed using the 35S promoter. We then explored the functions of OsCYP71 in the rice - Xanthomonas oryzae pv. oryzae pathosystem. Using the gene expression assays, we demonstrate the interesting correlation of PR gene activation and the magnitude of resistance in P450-mediated immunity.

Long-Term Feeding of Dietary Fat and Butylated Hydroxytoluene on The Hepatic Microsomal Mixed-Function Oxidase System in 2-Acetylaminofiuorene Treated Rats

  • Kim, Kyung-Min;Yim, Kyeong-Sook;Choi, Hay-Mie
    • Toxicological Research
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    • v.11 no.2
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    • pp.215-221
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    • 1995
  • This paper examines the effects of dietary polyunsaturated fatty acid/saturated fatty acid (p/s) ratios and butylated hydroxytoluene (BHT) on the hepatic microsomaI mixed-function oxidase sy. stem in 2~acetylaminofiuorene (2-AAF) treated rats. Sprague-Dawley male rats were fed the diet of beef tallow (p/s 0.08), beef tallow plus soybean oil (p/s 1.0), and soybean oil (p/s 4.0) at the level of 15%fat and with or without 0.3% BHT. After 2-AAF was injected twice at the ages of 23 and 27 weeks, cholesterol/phospholipid molar ratio, thiobarbituric acid reactive substances (TBARS) level, cytochrome P450, cytochrome $b_5$, NADPH-cytochrome $b_5$, and NADPH-cytochrome c reductase activity were measured from isolated hepatic microsomal fractions. In the beef tallow (p/s 0.08) and beef tallow plus soybean oil (p/s 1.0) groups, cholesterol/phospholipid molar ratio showed decreasing tendency by 2-AAF and BHT. Cytochrome P-450 content was decreased in the group of soybean oil (p/s 4.0) and NADPH-cytochrome c reductase activity was increased by 2-AAF and BHT in all the dietary groups. While TBARS levels were increased by 2-AAF in all the dietary groups, they were reduced by BHT in the soybean oil (p/s 4.0) group. These results suggest that long term intake of soybean oil (p/s 4.0) diet induced changes in the nature of microsomal membrane and induced less cytochrome P-450, low level feeding of BHT increased cytochrome c reductase activity and lowered microsomal lipid peroxidation levels, which were increased by 2-AAF treatment.

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The toxic effect of BPMC in rats (Rats에 있어서 BPMC투여에 의한 독성에 관한 연구)

  • 홍사욱;박승엽;김형식
    • Environmental Analysis Health and Toxicology
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    • v.7 no.3_4
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    • pp.57-67
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    • 1992
  • BPMC (2-Sec-butylphenyl N-methylcarbamate) was treated at the level of 100mg/kg/day in oral administration for 12th days in rat. It was investigated not only that the hematogram and the serological parameters, but also the content of cytochrome P-450, the activity of TBA, glucose-6-phosphatase, cholinesterase and carboxylesterase in rat. The results were as follows: The hematogram was not found any alteration but the value of AST, ALT, LDH and the content of glucose in serum were significantly increased compare with that of control group. The content of cytochrome P-450 in liver was increased significantly on the contrary cytochrome P-450 in kideny and NADPH-cytochrome c reductase in liver and Kidney were not significantly increased. After the final 12th day, the value of TBA and the activity of glucose-6-phosphatase appeared to the tendency of increasement in the liver. The activity of cholinesterase and carboxylesterase both in serum and liver were decreased. Especially the activity of cholinesterase was more significantly decreased. It was conclusion that the function of this insectivide should be due th the inhibition of cholinesterase activity.

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Toxic Effect of Combination of Buprofezin and Carbaryl in Rats (Buprofezin과 Carbaryl의 복합독성에 관한 연구)

  • 홍사욱;이종우
    • Environmental Analysis Health and Toxicology
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    • v.7 no.3_4
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    • pp.17-35
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    • 1992
  • In this study, it was examined the toxic effects of combination of buprofezin and carbaryl on hematological, biological and enzymetic parameters in rats. The administration of buprofezin or carbaryl both induced the tissue content of cytochrome P-450 and furthermore, the combination of the both increased significantly the liver content of cytochrome P-450 in rat. But cytochrome P-450 and NADPH -cytochrome c reductase activities in kidney were slightly increased. Administration of carbaryl and combination of the both also significantly increased hepatic aniline hydroxylase activity. In addition, in the combination group, glucose-6-phosphatase and lipid peroxidase activities were changed in the rat liver. Furthermore, cholinesterase was inhibited in rats treated with carbaryl or the combination of buprofezin and carbaryl. The above results suggested that the combined administration of buprofezin and carbaryl can induce more toxic effects than the single administration of buprofezin or carbaryl.

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Effects of γ-Irradiated Pork Diet on Cytochrome P-450 System, Microsome Glucose 6-Phosphatase Activity and Antioxidative Defense Systems in Rat Hepatocarcinogenesis

  • Kang, Il-Jun;Kim, Jung-Hee;Chung, Cha-Kwon
    • Preventive Nutrition and Food Science
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    • v.8 no.2
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    • pp.158-161
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    • 2003
  • This study investigated the effects of a ${\gamma}$-irradiated pork (0-30 kGy) diet on lipid peroxidation, cytochrome P-450 content, microsomal glucose 6-phosphatase (G-6-Pase) activity and antioxidative defense systems in diethylnitrosamine (DEN)-induced rat hepatocarcinogenesis. The body weight of rats fed irradiated diets did not change significantly. Liver weight was significantly increased by the administration of DEN, but not by irradiated diets at any dose level. There were no significant effects of gamma irradiation on the content of microsomal malondialdehyde (MDA), cytochrome P-450, or on the activity of G-6-Pase. However, with DEN treatment, cytochrome P-450 content was significantly increased while microsomal G-6-Pase activity was significantly decreased. The ${\gamma}$-irradiated diet supplement did not affect serum retinol or $\alpha$-tocopherol concentrations. However, it did cause a significant decrease in hepatic retinol at 30 kGy. With DEN treatment, hepatic retinol content was even more significantly (p<0.05) decreased compared to the non-irradiated control. The enzyme activities related to antioxidative defense systems, including glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rx) and glutathione S-transferase (GST) were not affected by gamma irradiation. Those results suggest that an irradiated pork diet up to 30 kGy may not cause a health hazard in experimental animals.

Responses in Hepatic Xenobiotic Metabolizing Enzymes and Sex Hormones of Yellowfin Goby Acanthogobius flavimanus in Nakdong Estuary (낙동강 하구에서 채집한 문절망둑 Acanthogobius flavimanus의 간장 약물대사효소계와 성호르몬 농도)

  • Lee, Ji-Seon;Jeong, Jee-Hyun;Han, Chang-Hee;Shim, Won-Joon;Jeon, Joong-Kyun
    • Korean Journal of Environmental Biology
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    • v.26 no.2
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    • pp.87-93
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    • 2008
  • To assess effects of contaminants on fish in Nakdong river, feral yellowfin goby Acanthogobius flavimanus were caugt in two different sites and its hepatic monooxygenase enzyme, including cytochrome P450 (CYP), NADPH-cytochrome P450 reductase (P450R), NADH-cytochrome b5 reductase (b5R), ethoxyresorufin deethylase (EROD), glutathione S-transferase (GST) were quantitatively determined. Gonadosomatic index (GSI), hepatosomatic index (HSI) and three sex steroid hormone (17$\beta$-estradiol, E2; testosterone, T; 11-ketotestosterone, 11-KT) levels of the fish were also investigated. HSI of fish from polluted site (site 1) were significantly higher than that of unpolluted site (site 2), but GSI levels were significantly lower in polluted site. No significant differences in plasma 11-KT and T levels were observed in two sites surveyed. E2 level was, however, significantly (p<0.05) higher in female fish from site 1 than site 2. In addition, hepatic EROD activity and CYP level of site 1 fish were lower than those of site 2 fish, whereas relatively high levels of P450R, b5R and GST activities were found in site 1. The results imply that yellowfin goby, especially female fish in Nakdong river estuary are affected from contaminants disrupting sex steroid hormone system.

Regulatory Mechanism of Cytochrome P450IIE in the Rat with Hepatic Injury and Ketosis (간장장해와 Ketosis시에 Cytochrome P450IIE의 Regulatory Mechanism에 관한 연구)

  • 윤여표;강원식;이세창;손동환
    • Journal of Environmental Health Sciences
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    • v.19 no.3
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    • pp.58-63
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    • 1993
  • In order to elucidate the alteration of drug-metabolizing enzymes and mechanism in the animal with hepatic injury and ketosis, the regulation of P450IIE was studied in the rats with heaptic injury caused by CCl$_4$ and with ketosis caused by streptozotocin and high-fat diet. P450IIE expression in liver was examined by the combination of enzyme activities, Western immunoblot, and mRNA Northern blot analyses using specific polyclonal antibody and cDNA probe for P450IIE. Enzyme activity and amounts of immunoreactive P450IIE were rapidly decreased in a time-dependent manner after a single dose of CCl$_4$ . However, the decreases in P450IIE enzyme activity and immunoreactive protein by CCl$_4$ were not accompanied by a decline in its mRNA level. The data thus suggested a post-translational reduction of P450IIE by CCl$_4$. The enzyme activities (aniline hydroxylase) in hepatic microsomes were elevated about 2-3-fold by streptozotocin and feeding with a high fat diet. This increases in enzyme activities were also accompanied by 3-fold increases in immunoreactive P450IIE protein and its mRNA. Our data thus indicated that P450IIE induction during the ketosis appears to be due to pretranslational activation.

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