• 제목/요약/키워드: Microsomal cytochrome P-450 monooxygenase

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Reponses of the Hepatic Microsomal Cytochrome P450 Monooxygenase System in Rock Bream Oplegnathus fasciatus Exposed to Tributyltin (TBT)

  • Hwang, Un-Gi;Lee, Jung-Sik;Kang, Ju-Chan
    • Fisheries and Aquatic Sciences
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    • 제16권4호
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    • pp.261-265
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    • 2013
  • The study was conducted to investigate the responses of the hepatic microsomal cytochrome P450 monooxygenase system in the rock bream Oplegnathus fasciatus after chronic exposure to 0, 1, 2, 4, and $8{\mu}g/L$ tributyltin (TBT) concentrations for 4 weeks. Hepatic cytochrome 450 content and ethoxyresorufin O-deethylation (EROD) activity were found to significantly increase in fish treated with the higher concentration of TBT (${\geq}4{\mu}g/L$); however, no significant changes were observed in penthoxyresorufin O-deethylation (PROD) activity in all treated groups compared to the control group. These findings suggest that exposure to a low TBT concentration (${\geq}4{\mu}g/L$) has the potential to induce cytochrome 450 content and EROD enzyme activity in hepatic tissue in the rock bream.

DIFFERENTIAL INDUCTION OF RAT LIVER MICROSOMAL CYTOCHROME-DEPENDENT MONOOXYGENASE AND UDP-GLUCURONOSYLTRANSFERASE ACTIVITIES BY VARIOUS NARCOTIC DRUGS

  • Hong, Young-Sook;Pae, Young-Sook
    • Toxicological Research
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    • 제5권1호
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    • pp.17-25
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    • 1989
  • Chronic adminstraction of morphine to adult male rats has long been known to lower hepatic cytochrome p-450 content and its dependent mixed-function oxidase activity. Following the treatment of adult male rats with morphine, pethidine pentazocine and codeine and also by concomitant adminstration of naloxone activities of microsomal electron transfer in the adult male rats were examined. In present study, the acute treatment of mature male rats with a dose of narcotic drugs higher than that used chronically also reduces their hepatic cytochrome p-450.

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생쥐에서 Cytochrome P-450 효소계에 의한 ${\alpha}$-Endosulfan의 시험관내 대사시험 (in Vitro Metabolism Study of ${\alpha}$-Endosulfan with Microsomal Cytochrome P-450 Monooxygenase)

  • 김인선;이강봉;심재한;서용택
    • Applied Biological Chemistry
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    • 제38권5호
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    • pp.463-467
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    • 1995
  • 생쥐(Balb/C) 간과 신장의 microsomal cytochrome P-450 효소계에 의한 ${\alpha}$-endosulfan의 시험관내 대사시험을 수행하였다. ${\alpha}$-Endosulfan은 endosulfan lactone(EL), endosulfan hydroxyether(EHE), endosulfan alcohol(EA), endosulfan sulfate(ES), endosulfan ether(EE) 그리고 ${\beta}$-endosulfan(${\beta}$-E) 등으로 대사되었으며 주요 대사산물은 간에서 EL(13.2%) 및 EA(11.5%)이었으며 신장에서 EA(17.4%) 및 EHE(19.3%)이었다. Microsome 배양액중 유기용매 추출성 대사산물은 63.4%이었으며 수용성 대사산물은 37.1%이었다. 수용성 대사산물은 EA(83.9%), EHE(4.5%) 그리고 ES(2.3%)로서 주요 수용성 대사산물은 EA이었다. Piperonyl butoxide는 ${\alpha}$-endosulfan으로부터 EE의 생성을 86%, EA의 생성을 92% 그리고 EHE, EL 및 ES의 생성을 대부분 저해하였다.

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Importance of Cytochrome P450 3A4 Conformation for the Activity Stimulation by Cytochrome b5 : Specific Inhibition of Cytochrome P450 3A4 by Zinc (II) Ion

  • Kim, Joon-Sik;Yun, Chul-Ho
    • 대한약학회:학술대회논문집
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    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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    • pp.149.3-150
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    • 2003
  • CYP3A4 is the most abundant human CYP and oxidizes a diversity of substrates. including various drugs. steroids. and carcinogens. A variety of metal ions are known to affect microsomal monooxygenase activities. Effects of a series of divalent metal ions on the CYP3A4-catalyzed reaction of reconstituted system containing purified CYP3A4. NADPH-P450 reductase (NPR), and cytochrome b5 (b5) were examined. (omitted)

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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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    • 제30권4호
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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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Metabolism-Dependent Cavalent Binding of $S(-)-^3H-Nicotine$ to Lung Microsomes in Vitro

  • Kim, Bong-Hee;Shingenaga, Mark-K.
    • Archives of Pharmacal Research
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    • 제16권2호
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    • pp.89-93
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    • 1993
  • Incubation of $S(-)-^3H$-nicotine with rabbit lung microsomes in the presence of dioxygen and NADPH results in the formation of metabolities that bind covalently to microsomal macro-molecules. The addition of cytochrome P-450 monooxygenase inhibitors, $\alpha$-methylbenzyl ami-nobenzotriazole and aroclor 1260, inhibited both (S)-nicotine metabolism and covalent binding. The relative rates of oxidation of nicotine $\Delta^{1',5'}$ iminium ion to continine indicates that lung $100,000\times{g}$ supematant catalyzed this oxidation approximately 18 times slower than that of liver system based on mg of protein, and increased covalent interactions. Since than that of liver system based on mg of protein, nd increased covalent interactions. Since the activity of lung iminium oxidase appears much lowr than the liver, it is tempting to speculate that localized concentrations of nicotine $\Delta^{1',5'}$ iminium ion in the lung will survive for a longer period of time. These results support that cytochrome P-450 catalyzed oxidation of nicotine leads to the formation of reactive nad electrophilic intemediates capable of chemical interactions with biomacromolecules.

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PCBs노출에 의한 틸라피아, Oreochromis niloticus의 간 cytochrome P450 효소계의 변화 (Changes of Hepatic Microsomal Cytochrome P450 Monooxygenase System in Nile tilapia, Oreochromis niloticus Exposed to PCBs)

  • 강주찬;조규석
    • 한국수산과학회지
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    • 제34권3호
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    • pp.194-198
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    • 2001
  • PCBs의 경구 투여에 의한 틸라피아, Oreochromis niloticus의 간 cytochrome P450 효소계의 변화를 30일간 관찰하였다. 30일 동안 PCBs 0.05, 0.25 및 0.50mg/kg을 투여했을 때, HSI는 각각 1.81, 1.72 및 $1.54\%$ 감소하였으나, 유의한 차이는 인정되지 않았다. PCBs 0.05mg/kg에 노출된 간 cytochrome P450 농도는 30일째 대조구에 비해 1.4배 유의한 증가를 나타냈고, 0.25mg/kg 이상에서는 실험 20일 이후부터 유의적으로 증가하였다. EROD 활성도는 PCBs 0.05 mg/kg에서 실험 30일째부터 유의하게 증가하여 약 8배 높게 나타났다. 또한, PCBs 0.25mg/kg이상에서는 실험 20일째부터 유의하게 증가하여 30일째부터는 각각 18 및 22배의 증가를 나타냈다. PROD는 PCBs $0.05\~0.50mg/kg$에 노출시킨 개체에서 $0.78\~1.93$pmole/mg protein이 측정되어 대조구에 비해 뚜렷한 변화는 관찰되지 않았다. 이상의 결과는 자연 수역에서 PCBs의 잔류에 따라 먹이를 통해 틸라피아의 체내에 적어도 0.05 mg/kg 이상이 30일간 이상 계속적으로 유입될 경우에 간 cytochrome P450농도 및 EROD 활성도는 증가될 것으로 추정된다.

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INDUCTION OF CYTOCHROME P-450 ASSOCIATED MONOOXYGENASE ACTIVITIES BY PHENOBARBITAL AND 3-METHYLCHOLANTHRENE IN PRIMARY CULTURES OF ADULT RAT HEPATOCYTES

  • Park, Seong-Kyu;Ha, Jong-Ryul;Kim, H.M.;Yang, K.H.
    • Toxicological Research
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    • 제3권1호
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    • pp.1-8
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    • 1987
  • In vitro induction of cytochrome 450 associated monooxygenase activities by phenobarbital (PB) and 3-methylcholanthrene (MC) was investigated in primary cultures of adult rat hepatocytes. PB and MC were added to the culture 24 hr after the initial plating of hepatocytes. A signiftcant increase of the activities of 7-ethoxycoumarin 0-deethylase and aryl hydrocarbon hydroxylase were observed in MC and PB treated culture. MC caused about 500% induction of the initial oxidation rates of both enzymes in 48 hr. However the PB maintained both enzyme activities close to the level of freshly isolated hepatocytes. Biphenyl 4-hydroxylase and aminopyrine N-demethylase activities were also induced by MC and PB. But the level of induction was less than that occuring with 7-ethoxycoumarin 0-deethylase and aryl hydrocarbon hydroxylase. When aflatoxin $B_1$ was added to the hepatocyte cultures which have been treated with MC or PB, it caused a significant increase of the unscheduled DNA synthesis at higher dose of aflatoxin $B_1$ as compared to those of untreated control hepatocyte cultures. The results suggest that microsomal enzyme activities can be selectively controlled preferably in hepatocyte cultures by the in vitro induction method. This principle may be useful for studying the metabolism and other toxicological studies.

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Detection of Wound-inducible Trans-Cinnamic Acid-4-Hydroxylase in Avocado, Persea americana, Roots

  • Joo, Eun-Young
    • Preventive Nutrition and Food Science
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    • 제2권4호
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    • pp.333-337
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    • 1997
  • Trans-cinnamic acid-4-hydroxylase(tC4H) is the first cytochrome P450-dependent monooxygenase of the phenylpropanoid pathway. The roots of avocado seedlings were wounded and examined to determine whether the tC4H would be activated in response to wounding and/or whether tC4H activity be modulated by the application of exogenous p-coumarate. At the specified length of times, the wounded and treated roots were either frozen in liquid nitrogen or used immediately to extract microsomal proteins. The microsomal proteins were subjected to immunoblot analysis using polyclonal antibodies against CYP73 of tC4H gene. In this study, tC4H was induced in wounded roots sealed in bags within 6 hours, and in low level({TEX}$10^{-8}${/TEX}M) of p-coumarate solution within 24 hours, whereas the olution without p-coumarate and high levels of p-coumarate solution repressed tC4H induction in wounded roots. These results indicate that tC4H is induced by wounding in the root of avocado, and is inhibited by the application of exogenous p-coumarate.

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

  • 임흥빈
    • 한국약용작물학회지
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    • 제15권6호
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    • pp.437-443
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    • 2007
  • 홍삼의 물추출물을 장기간 흰쥐에 급여했을 때 흰쥐 간의 이물질대사효소 활성도 유도에 미치는 영향을 조사하였다. 홍삼 물추출물의 급여농도는 25 mg/kg body weight이었으며, 간의 이물질대사효소 유도제는 항경련제 PB (80 mg/kg)와 발암제 3-MC (20 mg/kg)을 사용하였다. 간에서 이물질대사에 관여하는 cytochrome P-450의 함량, cytochrome P-450 dependent monooxygenase인 ECOD와 BPDM, cytochrome P-450 reductase와 GST의 활성도는 PB와 3-MC 투여에 의해서 대조군과 홍삼투여군 모두 크게 증가되었다. 흰쥐의 나이가 3개월에서는 두 유도제를 투여했을 때 이물질대사효소의 활성은 대조군이 인삼투여군에 비해 상대적으로 더 많이 유도되었다. 그러나 12개월에서는 두 시험군 모두 유도정도가 감소하였으나 홍삼투여군은 그 활성도 감소정도가 대조군에 비해 상대적으로 크지 않았다. 한편 두 그룹 모두 이물질대사 효소 중 cytochrome $B_5$ 함량과 cytochrome $b_5$ reductase의 활성도는 PB와 3-MC 투여에 의해서 뚜렷한 차이를 보이지 않았다. 따라서 이러한 결과는 흰쥐에 홍삼의 장기간 급여는 간에서 효소유도제의 이물질대사효소유도 정도를 조절하여 무독화에 기여할 수 있다는 것을 의미한다.