• Title/Summary/Keyword: Cytochrome P450 1B1

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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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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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    • v.5 no.1
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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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Inhibitory Effects of Medicinal Herbs on Cytochrome P450 Drug Metabolizing Enzymes (생약추출물의 Cytochrome P450 약물대사 효소계 저해활성)

  • Jeong, Hye-Gwang;You, Ho-Jin;Chang, Young-Su;Park, Sung-Jun;Moon, Young-Hee;Woo, Eun-Rhan
    • Korean Journal of Pharmacognosy
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    • v.33 no.1 s.128
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    • pp.35-41
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    • 2002
  • The MeOH ext., $CH_2Cl_2$ Frac., EtOAc Frac., n-BuOH Frac., and $H_2O$ Frac. of 23 Korean medicinal herbs were prepared and were tested the inhibitory effects on Cytochrome P450 (Cyp) 1A1/2, 2B1/2, 2E1. Among the tested samples, the extracts of Selaginella tamariscina, Euonymus alatus, Salvia miltiorhiza, Angelica acutiloba, Rheum palmatum, Paeonia moutan, Scutellaria barbata, Tribulus terrestris, Hedyotis diffusa, Curcuma zedoaria, Rehmania glutinosa, Trogopterus xanthipes, Melandryum firmum, Achyranthes bidentata, Leonurus sibricus, Panax ginseng, Paeonia lactiflora, Poncirus trifoliata, Cnidium officinale, Cyperus rotundus, Corydalis ternata showed significant inhibitory effects on Cyp 1A1/2, 2B1/2, 2E1. The $IC_{50}$ values of those extracts were found to be below $50\;{\mu}g/ml$.

Induction of Hepatic Microsomal Cytochrome P450 by N,N-dimethylformamide in Sprague-Dawley Rats (흰쥐에서 N,N-dimethylformamide에 의한 간장의 Microsomal Cytochrome P450의 유도)

  • Koh, Sang-Baek;Cha, Bong-Suk;Kang, Seung-Kyu;Joung, Hyo-Seok;Kim, Ki-Woong
    • Journal of Preventive Medicine and Public Health
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    • v.32 no.1
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    • pp.88-94
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    • 1999
  • Objectives. In order to gain a better understanding of the mechanism of DMF toxicity, recent studies have focused on hepatic drug metabolizing enzymes. In this study, we investigated the effects of DMF on the induction of P450 and the activities of other related enzymes in rat liver microsomes. Methods. DMF was administered to male Sprague Daweley rats by intraperitoneal injection at 0(control), 450(D1), 900(D2), 1,800(D3) mg DMF/kg body weight in olive oil once a day for three days. Hepatic P450 was measured by method of Omura and Sato. We evaluated selective assays for the three drug metabolizing cytochrome P450 isoenzymes 1A1, 2B1 and 2E1. Results. The content of microsomal protein, P450 and b5 were tended to be decreased in DMF treated group, but they were not statistically significant. The activity of NADPH-cytochrome P450 reductase was significantly increased dose dependently(p<0.01), but the activity of NADH-b5 reductase was decreased in the treated group(p<0.01). The activities of PROD and EROD were not significant between control and treated group. The activities of pNPH in the DMF treated groups were higher than that of the control group(p<0.01). When Western immunoblottings were carried out utilizing three monoclonal antibodies which were specific against P4501A1/1, P4502B1/2 and P4502E1, the strong density band corresponding to P4502E1 was observed with the microsomes obtained from the rats treated with DMF. But there were no significant increased in the P4501A1/2 and P4502B1/2 band densities in immunoblotting. Conclusions. These result suggested that P4502E1 was inducible by DMF and P4502E1 isozyme might be responsible for the hydroxylation of DMF to HMMF.

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Cytochrome P450 1 gene in Eel, Anguilla japonica: cloning and expression patterns after exposure to benzo[a]pyrene (뱀장어(Anguilla japonica)에서 Cytochrome P450 1 gene 클로닝 및 benzo[a]pyrene 노출에 따른 발현 분석)

  • Jo, Hyun Ho;Kim, Ju An;Lee, Seung Hyun;Chung, Joon Ki
    • Journal of fish pathology
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    • v.33 no.2
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    • pp.153-161
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    • 2020
  • Cytochrome P450(CYP) gene is involved in the biotransformation of drugs and environmental pollutants. In this study, we analyzed the nucleotide sequence of the Anguilla japonica CYP1(AjCYP1) family gene and examined the relative expression of AjCYP1A, AjCYP1B and AjCYP1C1 in response to the exposure to environmental pollutants. After exposure to B[a]P 20mg/kg bw, the expression of AjCYP1 family gene increased over time. Among four tissues examined (liver, spleen, gill and kidney), AjCYP1 family gene was expressed significantly in the kidney. Compared with the control group, AjCYP1A was expressed about 5-fold at 48 hr, AjCYP1B about 6-fold at 24 hr, and AjCYP1C1 about 4-fold at 24 hr. However, after exposure to B[a]P 200mg/kg bw, AjCYP1A did not change in all tissues. On the other hand, AjCYP1B was expressed at about 4-fold at 24 hr in the spleen and 4-fold at 48 hr in the gill. Finally AjCYP1C1 was expressed 3.7-fold and 4.3-fold in the spleen and kidneys at 48 hr, respectively. Taken together, our results suggest that the expression of AjCYP1 gene in eel tissues might be used as a useful tool to assess the exposure to environmental pollutants in aquaculture system.

Preventive Effect of Sarcodon aspratus Extract on the Liver Damage in B(a)P-Treated Mice (벤조피렌을 투여한 마우스에서 향버섯 추출물의 간 손상 예방 효과)

  • 이갑랑;배준태;장종선;박준홍;박선희;김지영;오은정;김현정;김옥미
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.30 no.2
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    • pp.320-324
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    • 2001
  • To investigate the effect of Sarcodon aspratus methanol extract on liver damage in benzo(a)pyrene (B(a)P)-treated mice, mice were divided into 4 groups of control, B(a)P, Sarcodon aspratus methanol extract and Sarcodon aspratus methanol extract-B(a)P. The activities of serum aminotransferase, cytochrome P-450 and hepatic content of lipid peroxide after B(a)P-treatment were increased than control, but those levels were significantly decreased by the treatment of Sarcodon aspratus methanol extract. On the other hand, the hepatic glutathione content and glutathione S-transferase activity were increased by the treatment of Sarcodon aspratus methanol extract. Also the activities of superoxide dismutase, catalase and glutathione peroxidase were decreased by the treatment of Sarcodon aspratus methanol extract. In addition cytochrome P-450 1A1 isozyme protein level, which was remarkably increased by B(a)P treatment from results of immuno blotting, was decreased by the treatment with methanol extract of Sarcodon aspratus. These results suggest that Sarcodon aspratus methanol extract have protective effect on liver damage by decreasing lipid peroxide and activities of free radical generating enzymes.

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Effects of Several Inhibitors of Human Liver Microsomal Cytochrome P450 3A4 on Catalytic Activities of the Enzyme (인체 간 조직의 cytochrome P450 3A4의 활성에 대한 몇가지 억제제의 영향)

  • 오현숙;이갑상;김복량
    • Toxicological Research
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    • v.11 no.1
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    • pp.23-29
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    • 1995
  • Microsomes from human liver sample HL 110 oxidized aflatoxin $B_1$ $(AFB_1)$ to $AFB_1$ exo-8, 9-epoxide which was detected as a glutathione (GSH) conjugate with excess GSH S-transferase and to aflatoxin $Q_1$ ($AFB_1$; 3$\alpha$-hydroxyafiatoxin $B_1$), and testosterone to 6$\beta$-hydroxytestosterone. Anti-P450 3A4 nearly completely inhibited all of the reactions. Some fiavonoids inhibited all of the reactions. While other fiayonolds stimulated 8, 9-epoxidation and inhibited 3$\alpha$-hydroxylation. Gestodene inhibited all of the reactions when gestodene was metabolized by human liver microsomal P450 3A4 prior to adding substrate. But, ges-todene was added in the enzyme mixtures in the presence of $AFB_1$, it could not inhibit 8, 9-epoxidation of $AFB_1$. Nifedipine and troleandomycin inhibited both of the reactions of $AFB_1$ but only 3$\alpha$-hydroxylation was inhibited by the oxidation product of nifedipine. Although, troleandomycin was known as a mechanism-based inhibitor, the chemical did not show any detectable inhibitory effect on 6$\beta$-hydroxylation of testosterone. The results suggest that there are several different substrate-binding sites on P450 3A4.

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Microsomal Mixed Function Oxidase and Lipid Peroxidation in Liver and Lung of Sterptozotocin-Induced Diabetic Rats (Streptozotocin 유발 당뇨쥐의 간장 및 폐조직에서의 Microsomal Mixed Function Oxidase System과 과산화지질 생성)

  • 이순재;김관유
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.25 no.1
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    • pp.21-26
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    • 1996
  • 본 연구는 streptozotocin 유발 당뇨쥐에서의 MFO계활성 변화 및 이에 지질과산화를 관찰하고자 체중이 140kg 내외의 Sprague-Dawley 종 흰쥐 숫컷을 대조군과 당뇨 유발 시험군으로 나누어 4주간 사육하였다. 당뇨군은 STZ로 당뇨를 유발시켰으며 당뇨 유발 6일후 쥐를 희생기켜 간조직 및 폐조직 microsome 중의 cytochrome $P_{450}$ 및 cytochrome $b_[5}$ 함량과 NADPH-cytochrome $P_{450}$ reductase 활성도를 측정하고 아울러 microsome내의 지질과산화물을 측정하여 다음과 같은 결과를 얻었다. 실험군간에 식이 섭취량은 차이가 없었으나, 체중 증가량과 식이 효율은 당뇨군이 STZ군에 비해 현저하게 감소하였다. 간장 및 폐조직의 무게는 대조군과 당뇨군간에 유의적인 차이는 없었다. 간조직 및 GP조직 중의 cytochrome $P_{450}$ 함량은 대조군에 비해 당뇨군이 150%, 175%씩 증가하였다. 간조직 및 폐조직 중의 cytochrome $b_{5}$은 대조군에 비해 당뇨군이 53%,116%씩 각각 증가하였다. 간조직에서의 NADPH-cytochrome $P_{450}$ reductase 활성은 당뇨군이 대조군에 비해 46% 증가하였으며, 폐조직에서는 75%증가하였다. 지질과산화물가는 당뇨군이 대조군에 비해 간족에서는 약 95% 높았으며 폐조직에서는 73%높았다. 이상의 결과에서 STZ 유발 당뇨쥐에서는 MFO system의 활성도가 대조군에 비해 현저하게 증가되고 지질과산화반응이 같으 srudgid이 촉진되었으며 폐조직에서도 간조직에서와 비슷한 경향이었다. 이러한 것은 당뇨군에서는 MFO system의 활성증가로 free radical 생성이 증가되고 그 결과 지질과산화가 촉진되었다고 볼 수 있다.

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Effect of Benzo[a]pyrene on Genes Related to the Cell Cycle and Cytochrome P450 of Saccharomyces cerevisiae

  • Lee, Hyun-Joo;Gu, Man-Bock
    • Journal of Microbiology and Biotechnology
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    • v.13 no.4
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    • pp.624-627
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    • 2003
  • Benzo[a]pyrene (B[a]P) is an environmental pollutant that has been implicated in carcinogenesis. Saccharomyces cerevisiae was treated with B[a]P, and the responses of its cytochrome P450 (CYP) enzyme and DNA-damage checkpoint genes were examined through gene expression profiles using a reverse transcription polymerase chain reaction (RT-PCR). The DNA-damage checkpoint genes tested were the chk1 and pds1 genes, involved in a metaphase arrest, the swi6 gene targeted by G1 arrest, the pol2 gene related to S phase arrest, and the cln2 gene encoding a cyclin protein, all of which are based on rad9 and rad24. Among these genes, no noticeable effect was found when the cells were exposed to various concentrations of B[a]P. However, the transcriptional activity of CYP51 was significantly different when the cells were exposed to B[a]P. Accordingly, the present results indicate that cytochrome P450 plays a more significant role than DNA-damage checkpoint genes in the response of S. cerevisiae to B[a]P.

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.