• BMB Reports
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• v.41 no.6
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• pp.472-478
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• 2008

Three Arabidopsis cDNAs, MAM1, CYP79F1, and CYP83A1, required for aliphatic glucosinolate biosynthesis were introduced into Chinese cabbage by Agrobacterium tumefaciens-mediated transformation. The transgenic lines overexpressing MAM1 or CYP83A1 showed wild-type phenotypes. However, all the lines overexpressing CYP79F1 displayed phenotypes different from wild type with respect to the stem thickness as well as leaf width and shape. Glucosinolate contents of the transgenic plants were compared with those of wild type. In the MAM1 line M1-1, accumulation of aliphatic glucosinolates gluconapin and glucobrassicanapin significantly increased. In the CYP83A1 line A1-1, all the aliphatic glucosinolate levels were increased, and the levels of gluconapin and glucobrassicanapin were elevated by 4.5 and 2 fold, respectively. The three CYP79F1 transgenic lines exhibited dissimilar glucosinolate profiles. The F1-1 line accumulated higher levels of gluconapoleiferin, glucobrassicin, and 4-methoxy glucobrassicin. However, F1-2 and F1-3 lines demonstrated a decrease in the levels of gluconapin and glucobrassicanapin and an increased level of 4-hydroxy glucobrassicin.

• Journal of Marine Life Science
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• v.8 no.2
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• pp.104-114
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• 2023

As plastic usage increases globally, the amount of plastic waste entering the marine environment is steadily rising. Microplastics, in particular, can be ingested by marine organisms and accumulated in their digestive tracts, causing harmful effects on their growth and reproduction. Cytochrome P450 (CYP) enzymes are known to metabolize various environmental pollutants as detoxification enzymes, but their role in crustaceans is not well understood. In this study, sequences of nine CYP genes (CYP370A4, CYP370C5 from clan 2; CYP350A1, CYP350C5, CYP361A1 from clan 3; CYP4AN-like, CYP4AP2, CYP4AP3, CYP4C33-like1 from clan 4) were analyzed using conserved domains in the brackish water flea Diaphanosoma celebensis. Additionally, after exposure to three different sizes of polystyrene beads (0.05-, 0.5-, 6-㎛ PS beads; 0.1, 1, and 10 mg/L) for 48 hours, the expression of these nine CYP genes were investigated using real-time reverse transcription polymerase chain reaction (RT-PCR). The results showed that all CYP genes possessed conserved motifs, indicating that D. celebensis CYP has evolutionarily conserved functions. Among these CYP genes, the expression of CYP370C5, CYP360A1, and CYP4C122 showed a significant increase after exposure to 0.05-㎛ PS beads, suggesting their involvement in PS metabolism. This research will contribute to understanding the molecular mode of actions of microplastics on marine invertebrates.

• Environmental Mutagens and Carcinogens
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• v.24 no.3
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• pp.143-150
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• 2004

In mammalian, cytochrome P4501A1 (CYP1A1) is very important for metabolism of xenobiotics such as PAHs(Polycyclic aromatic hydrocarbon) and heterocyclic amine, and it is induced by environmental contaminants such as PAHs, TCDD(2,3,7,8-tetrchlorodibenzo-p-dioxin) and 3-MC (3-methylcholanthrene). In fish, like mammalian, when it is exposed to environmental contaminants, they cause specific and sensitive induction of CYP1A. Therefore, induction of CYP1A in fish and mammalian is widely used as a biomarker for exposure of environmental contaminants. In this study, to compare the function of Cyp1a1 in fish with it in mammalian, we have used rainbow trout(Oncorhynchys mykiss) hepatoma cells (RTH-149) and mouse hepatocyte (Hepa-I). in order to examine induction of Cyp1a1 by TCDD, we have used the bioassay system. We examined effects of TCDD on the Cyp1a1-luciferase reporter gene activity, 7-ethoxyresorufin O-deethylase(EROD) activity and Cypa mRNA level.

• Archives of Pharmacal Research
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• v.27 no.2
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• pp.232-238
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• 2004

Trolox is a hydrophilic analogue of vitamin E. The aim of this study was to investigate its effects on hepatic injury, especially alteration in cytochrome P450 (CYP)-dependent drug metabolism during polymicrobial sepsis. Rats were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP). The rats were treated intravenously with Trolox (2.5 mg/kg) or vehicle, immediately after CLP. Serum aminotransferases and lipid peroxidation levels were markedly increased 24 h after CLP. This increase was attenuated by Trolox. Total CYP content and NADPH-P450 reductase activity decreased significantly 24 h after CLP. This decrease in CYP content was attenuated by Trolox. At 24 h after CLP, there was a significant decrease in the activity of these CYP isozymes: CYP1A1, 1A2, 2B1, and 2E1. However, Trolox differentially inhibited the decrease in CYP isozyme activity. Trolox had little effect on the decrease in CYP1A1 activity but Trolox significantly attenuated decreases in CYP1A2 and 2E1 activities. In fact, Trolox restored CYP2B1 activity to the level of activity found in control rats. Our findings suggest that Trolox reduces hepatocellular damage as indicated by abnormalities in hepatic drug-metabolizing function during sepsis. Our data also indicates that this protection is, in part, caused by decreased lipid peroxidation.

• Toxicological Research
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• v.9 no.2
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• pp.153-158
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• 1993

Pyridine and acetone are efficacious inducers of CYP2E1 in both rats and rabbits. The response in the elevation of CYP2E1 levels, changes in CYP2E1 mRNA levels, and enhanced translational processing of hepatic CYP2E1 mRNA during the early phase of CYP2E1 induction by the solvents pyridine and acetone were examined. Time-depen-dent incease in CYP2E1 levels occurred at early times (6-24h) following a single dose of pyridine treatmene, as assessed by Western immunoblot analysis, whereas the levels in CYP2E1 mRNA transiently decreased at 12h post-treatment, returning to the level present in untreated animals.

• Journal of Microbiology and Biotechnology
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• v.22 no.12
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• pp.1659-1664
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• 2012

TSAHC [4'-(p-toluenesulfonylamido)-4-hydroxychalcone] is a promising antitumorigenic chalcone compound, especially against TM4SF5 (four-transmembrane L6 family member 5)-mediated hepatocarcinoma. We evaluated the potential of TSAHC to inhibit the catalytic activities of nine cytochrome P450 isoforms and of P-glycoprotein (P-gp). The abilities of TSAHC to inhibit phenacetin O-deethylation (CYP1A2), coumarin 6-hydroxylation (CYP2A6), bupropion hydroxylation (CYP2B6), amodiaquine N-deethylation (CYP2C8), diclofenac 4-hydroxylation (CYP2C9), omeprazole 5-hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), and midazolam 1'-hydroxylation (CYP3A) were tested using human liver microsomes. The P-gp inhibitory effect of TSAHC was assessed by [$^3H$]digoxin accumulation in the LLCPK1-MDR1 cell system. TSAHC strongly inhibited CYP2C8, CYP2C9, and CYP2C19 isoform activities with $K_i$ values of 0.81, 0.076, and $3.45{\mu}M$, respectively. It also enhanced digoxin accumulation in a dose-dependent manner in the LLCPK1-MDR1 cells. These findings indicate that TSAHC has the potential to inhibit CYP2C isoforms and P-gp activities in vitro. TSAHC might be used as a nonspecific inhibitor of CYP2C isoforms based on its negligible inhibitory effect on other P450 isoforms such as CYP1A2, CYP2A6, CYP2B6, CYP2D6, CYP2E1, and CYP3A.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.169-169
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• 2003

CYP1 enzymes, CYP1A1, CYP1A2 and CYP1B1, are known to bioactivate procarcinogens particularly polyaromatic compounds. Flavonoids are a class of natural compounds that are present in edible plants. Structurally, these compounds are polyphenols with two aromatic rings (A, B) and a heterocycyclic ring (C).(omitted)

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2647-2653
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• 2012

Involvement of cytochrome P450 genes (CYPs) in breast cancer (BCa) may differ between populations, with expression patterns affected by tumorigenesis. This may have an important role in the metabolism of anticancer drugs and in the progression of cancer. The aim of this study was to determine the mRNA expression patterns of four cytochrome P450 genes (CYP2W1, 3A5, 4F11 and 8A1) in Mexican women with breast cancer. Real-time PCR analyses were conducted on 32 sets of human breast tumors and adjacent non-tumor tissues, as well as 20 normal breast tissues. Expression levels were tested for association with clinical and pathological data of patients. We found higher gene expression of CYP2W1, CYP3A5, CYP4F11 in BCa than in adjacent tissues and only low in normal mammary glands in our Mexican population while CYP8A1 was only expressed in BCa and adjacent tissues. We found that Ki67 protein expression was associated with clinicopathological features as well as with CYP2W1, CYP4F11 and CYP8A1 but not with CYP3A5. The results indicated that breast cancer tissues may be better able to metabolize carcinogens and other xenobiotics to active species than normal or adjacent non-tumor tissues.

• Natural Product Sciences
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• v.10 no.5
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• pp.197-206
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• 2004

Cytochrome P4501A2 (CYP1A2) is responsible for the metabolic activation of a number of aromatic amines and amides to mutagenic and carcinogenic moieties. Considerable variations in the level of CYP1A2 expression in humans have been reported. Thus, the level of human CYP1A2 may determine an individuals susceptibility to these chemicals. Given its importance, the molecular mechanisms of CYP1A2 regulation have been studied by many groups. Direct interactions between transcription factors with the promoters of the gene represent one of the primary means by which the expression of CYP1A2 is controlled. In this review, several important cis elements, transcription factors and the effects of deacetylation/methylation of promoter regions that play an important role in the induction by PAHs as well as constitutive expression of human CYP1A2 are discussed.

• YAKHAK HOEJI
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• v.57 no.3
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• pp.194-198
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• 2013

In the present study we evaluated drug-drug interaction potential of ambroxol and cetirizine mediated by inhibition of CYP isoforms including CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 using pooled human liver microsomes (HLMs). As measured by liquid chromatography-electrospray ionization tandem mass spectrometry, cetirizine and ambroxol inhibited significantly CYP2E1 but the maximal inhibition was approximately 36% at 10 ${\mu}M$ cetirizine and 28% at 3 ${\mu}M$ ambroxol. In addition, CYP2D6 activity was decreased to approximately 83% of control activity in pooled HLM incubated with 3 ${\mu}M$ ambroxol. Activities of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, and CYP3A4 were not significantly inhibited by cetirizine and ambroxol. Considering their maximal plasma concentration in human ($C_{max}$ of cetirizine is approximately 0.67 ${\mu}M$ and $C_{max}$ of ambroxol is 0.044 ${\mu}M$), these two drugs have very low possibility in drug-drug interaction by CYP inhibition in clinical situations.