• Title/Summary/Keyword: CYP1A2

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Effect of methyl jasmonate on the glucosinolate contents and whole genome expression in Brassica oleracea (유묘기 양배추류에서 메틸자스모네이트에 의한 글루코시놀레이트 함량 변화 및 전사체 발현 분석)

  • Lee, Jeongyeo;Min, Sung Ran;Jung, Jaeeun;Kim, HyeRan
    • Journal of Plant Biotechnology
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    • v.46 no.3
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    • pp.189-204
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    • 2019
  • In this study, we analyzed the changes in glucosinolate content and gene expression in TO1000DH3 and Early big seedling upon methyl jasmonate (MeJA) treatment. Analysis of glucosinolate contents after MeJA treatment at $200{\mu}M$ concentration showed that the total glucosinolate content increased by 1.3-1.5 fold in TO1000DH3 and 1.3-3.8 fold in Early big compared to those before treatment. Aliphatic glucosinolates, progoitrin and gluconapin, were detected only in TO1000DH3, and the changes in the content of neoglucobrassicin were the greatest at 48 hours after MeJA treatment in TO1000DH3 and Early big. The transcriptomic analysis showed that transcripts involved in stress or defense reactions, or those related to growth were specifically expressed in TO1000DH3, while transcripts related to nucleosides or ATP biosynthesis were specifically expressed in Early big. GO analysis on transcripts with more than two-fold change in expression upon MeJA treatment, corresponding to 12,020 transcripts in TO1000DH3 and 13,510 transcripts in Early big, showed that the expression of transcripts that react to stimulus and chemical increased in TO1000DH3 and Early big, while those related to single-organism and ribosome synthesis decreased. In particular, the expression increased for all transcripts related to indole glucosinolate biosynthesis, which is associated with increase in glucobrassicin and neoglucobrassicin contents. Upon MeJA treatment, the expression of AOP3 (Bo9g006220, Bo9g006240), TGG1 (Bo14804s010) increased only in TO1000DH3, while the expression of Dof1.1 (Bo5g008360), UGT74C1 (Bo4g177540), and GSL-OH (Bo4g173560, Bo4g173550, Bo4g173530) increased specifically in Early big.

Regulation of CYP1A1 and Inflammatory Cytokine by NCOA7 Isoform 4 in Response to Dioxin Induced Airway Inflammation

  • Cho, Sung-Hwan;Park, Shin Young;Lee, Eun Jeong;Cho, Yo Han;Park, Hyun Sun;Hong, Seok-Ho;Kim, Woo Jin
    • Tuberculosis and Respiratory Diseases
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    • v.78 no.2
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    • pp.99-105
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    • 2015
  • Background: Aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, binds to a wide variety of synthetic and naturally occurring compounds. AhR is involved in the regulation of inflammatory response during acute and chronic respiratory diseases. We investigated whether nuclear receptor coactivator 7 (NCOA7) could regulate transcriptional levels of AhR target genes and inflammatory cytokines in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treated human bronchial epithelial cells. This study was based on our previous study that NCOA7 was differentially expressed between normal and chronic obstructive pulmonary disease lung tissues. Methods: BEAS-2B and A549 cells grown under serum-free conditions were treated with or without TCDD (0.15 nM and 6.5 nM) for 24 hours after transfection of pCMV-NCOA7 isoform 4. Expression levels of cytochrome P4501A1 (CYP1A1), IL-6, and IL-8 were measured by quantitative real-time polymerase chain reaction. Results: The transcriptional activities of CYP1A1 and inflammatory cytokines were strongly induced by TCDD treatment in both BEAS-2B and A549 cell lines. The NCOA7 isoform 4 oppositely regulated the transcriptional activities of CYP1A1 and inflammatory cytokines between BEAS-2B and A549 cell lines. Conclusion: Our results suggest that NCOA7 could act as a regulator in the TCDD-AhR signaling pathway with dual roles in normal and abnormal physiological conditions.

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.

Effects of Apigenin, a Flavonoid, on the Bioavailability of Tamoxifen in Rats (흰쥐에서 아피제닌이 타목시펜의 생체이용률에 미치는 영향)

  • Kim, Yang-Woo;Choi, Jun-Shik
    • YAKHAK HOEJI
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    • v.54 no.5
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    • pp.370-376
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    • 2010
  • The aim of this study is to investigate the effect of apigenin on the pharmacokinetics of tamoxifen in rats. Tamoxifen was administered orally (10 mg/kg) or intravenously (2 mg/kg) without or with oral administration of apigenin (0.4, 2.0 or 8.0 mg/kg) to rats. The effect of apigenin on the P-glycoprotein (P-gp) and CYP3A4 activity was also evaluated. Apigenin inhibited CYP3A4 enzyme activity with 50% inhibition concentration ($IC_{50}$) of 1.8 ${\mu}M$. In addition, apigenin significantly enhanced the cellular accumulation of rhodamine 123 in MCF-7/ADR cells overexpressing P-gp. The plasma concentrations of tamoxifen were increased significantly by apigenin compared to control. The areas under the plasma concentration-time curve (AUC) and the peak concentrations ($IC_{max}$) of tamoxifen with apigenin were significantly higher than those of the control group. Consequently, the relative bioavailability (RB%) of tamoxifen with apigenin was 2-3-fold higher than the control, and absolute bioavailability (AB%) of tamoxifen were significantly higher (p<0.05 with co-administration, p<0.01 with pretreatment) than those of the control. The increased bioavailability of tamoxifen in rats with apigenin might be associated with the inhibition of an efflux pump P-glycoprotein and CYP3A4 by apigenin. From these results, dosage regimen of tamoxifen may be need to adjust when concomitantly administered with apigenin.

THE EFFECT OF COPROPHAGY ON THE EXPRESSION OF HEPATIC CYP2E1 DURING STARVATION

  • Chung, Hye-Chin;Sung, Sang-Hyun;Kim, Jin-Soo;Kim, Young-Choong;Kim, Sang-Geon
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.05a
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    • pp.141-141
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    • 2001
  • Starvation stimulates multiple signaling pathways, which lead to extensive metabolic alterations Starvation potentiates the hepatotoxicity of a variety of small molecules including chlorinated hydrocarbons and nitrosamines through the induction of CYP2E1. A change in CYF2E1 expression during starvation may also alter the pharmacokinetic profiles of xenobiotics.(omitted)

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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.