• Title/Summary/Keyword: P450 1A2

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Identification of HYIpro-3-1 Metabolites, a Novel Anti-Inflammatory Compound, in Human Liver Microsomes by Quadrupole-Orbitrap High-Resolution Mass Spectrometry

  • Bai, Honghao;Kim, Younah;Paudel, Sanjita;Lee, Eung-Seok;Lee, Sangkyu
    • Mass Spectrometry Letters
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    • v.12 no.4
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    • pp.172-178
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    • 2021
  • HYIpro-3-1 is an adjuvant for preventing or treating inflammatory growth diseases. In this study, we identified the metabolic pathway of HYIpro-3-1 in human liver microsomes (HLMs) by quadrupole-orbitrap high-resolution mass spectrometry (HR-MS) and characterized the major human cytochrome P450 (CYP). Ten metabolites were identified, including one O-demethylation (M1), two O-demethylation and monohydroxylation (M2 and M3), and seven monohydroxylation metabolites (M4-M10). Based on the HR-MS2 spectra, the metabolites are divided into two groups of monohydroxylated metabolites according to the hydroxylation position. We verified that HYIpro-3-1 is metabolized by CYP in HLMs, CYP2B6 is mainly involved in O-demethylation, and various CYPs are involved in the monohydroxylation of HYIpro-3-1.

Hangover relieving effect of Sanghwang mushroom mycelium cultured in germinated buckwheat

  • An, Yoo-Jin;Cho, Sung-Min;Kim, Min-Su;Moon, Hae-Hee;Park, Dong-Soo;Jeon, Nam-Gen;Lee, oungjae;Han, Chang-Hoon
    • Korean Journal of Veterinary Research
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    • v.57 no.3
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    • pp.147-154
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    • 2017
  • The present study was performed to evaluate the hangover relieving effect of germinated buckwheat (GB) and Sanghwang mushroom mycelium cultured in GB (SGB). Both GB and SGB showed 1,1-diphenyl-2-picrylhydrazyl radical scavenging activities and significantly increased (p < 0.001) aldehyde dehydrogenase (ALDH) activities; up to 140% increase at concentrations of $16{\mu}L/mL$. Locomotor activity test results from alcohol-SGB and alcohol-GB groups showed improved motor activities over that of the alcohol-water group at 90 min post-administration. Both alcohol-GB and alcohol-SGB groups had significantly reduced (p < 0.001) alcohol ($40.02{\pm}33.38{\mu}g/mL$, $66.01{\pm}22.04{\mu}g/mL$, respectively) and aldehyde ($5.72{\pm}0.47{\mu}g/mL$, $6.72{\pm}1.70{\mu}g/mL$, respectively) concentrations in blood compared to those in the alcohol-water group ($199.75{\pm}33.83{\mu}g/mL$, $50.43{\pm}13.88{\mu}g/mL$, respectively) at 90 min post-administration. Based on cDNA microarray analysis, expressions of ALDH genes ALDH1a7 and ALDH18a1 and cytochrome P450 (CY450) gene CYP4a30b were upregulated in the alcohol-GB and alcohol-SGB groups compared to levels in the control group. Overall, the results suggest that both GB and SGB have hangover relieving effects by reducing blood acetaldehyde levels. The molecular mechanisms may involve ALDH activation and upregulated expression of alcohol metabolism-related genes such as ALDH and CYP450.

Diagnosis of Lily Plant Fasciation Caused by Rhodococcus fascians in Jeju Island

  • Yong Ho Shin;Min Ju Choi;Hyun Su Kang;Yong Chull Jeun
    • Research in Plant Disease
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    • v.29 no.1
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    • pp.39-44
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    • 2023
  • To diagnose lily fasciation, lily bulbs showing fasciation were collected from several greenhouses in Jeju Island, South Korea. Bacteria were isolated from the lily bulbs and amplified with both primers for fasA in plasmid and for putative glycosyltransferase epsH gene in chromosome of Rhodococcus fascians. Three bacterial isolates were detected with the P450 primer set and identified as R. fascians by NCBI blast analysis. Twelve bacterial isolates were identified as R. fascians using RS02785 primer set, including the three bacterial isolates identified as the same pathogen using the P450 primer set. Pathogenicity of these bacterial strains identified as R. fascians was demonstrated. Apparent symptoms were observed on wounded lily leaves after inoculation with each bacterial suspension whereas no symptom was found on lily leaves treated with H2O. Furthermore, bacteria re-isolated from wounded sites were identified as R. fascians. Based on the results, these two sets of primers are recommended for quarantine of R. fascians.

Luminescence of CaS:Bi

  • 김창홍;편종홍;최 한;김성진
    • Bulletin of the Korean Chemical Society
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    • v.20 no.3
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    • pp.337-340
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    • 1999
  • Luminescence of bismuth activated CaS, CaS:Bi, prepared in sodium polysulfide is studied. Excitation spectrum of CaS:Bi shows a band at 350 nm due to the recombination process between holes in Na+Ca2+ and electrons in conduction bands, in addition to bands at 260 nm from band gap of CaS, and at 320 nm (1S0→1P1) and at 420 nm (1S0→3P1) from electronic energy transitions of Bi. Emission band at 450 nm is from 3P1→1S0 transition of Bi3+, bands at 500 nm and 580 nm correspond to recombinations of electron donors (Bi3+Ca2+ and VS2-) with acceptors (VCa2+ and Na+Ca2+). Emission band of 3P1→1S0 transition is shifted to longer wavelength from CaS:Bi to BaS:Bi, due to the increase of the Stokes shift by the decrease of the crystal field parameter from CaS:Bi to BaS:Bi.

Pharmacogenomics and Schizophrenia (약물유전체학과 정신분열병)

  • Lee, Kyu Young;Chung, In Won
    • Korean Journal of Biological Psychiatry
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    • v.8 no.2
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    • pp.208-219
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    • 2001
  • The pharmacotherapy of schizophrenia exhibits wide inter-individual variabilities in clinical efficacy and adverse effects. Recently, human genetic diversity has been known as one of the essential factors to the variation in human drug response. This suggests that drug therapy should be tailored to the genetic characteristics of the individual. Pharmacogenetics is the field of investigation that attempts to elucidate genetic basis of an individual's responses to pharmacotherapy, considering drug effects divided into two categories as pharmacokinetics and pharmacodynamics. The emerging field of pharmacogenomics, which focuses on genetic determinants of drug response at the level of the entire human genome, is important for development and prescription of safer and more effective individually tailored drugs and will aid in understanding how genetics influence drug response. In schizophrenia, pharmacogenetic studies have shown the role of genetic variants of the cytochrome P450 enzymes such as CYP2D6, CYP2C19, and CYP2A1 in the metabolism of antipsychotic drugs. At the level of drug targets, variants of the dopamine $D_2$, $D_3$ and $D_4$, and 5-$HT_{2A}$ and 5-$HT_{2C}$ receptors have been examined. The pharmacogenetic studies in schizophrenia presently shows controversial findings which may be related to the multiple involvement of genes with relatively small effects and to the lack of standardized phenotypes. For further development in the pharmacogenomics of schizophrenia, there would be required the extensive outcome measures and definitions, and the powerful new tools of genomics, proteomics and so on.

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Effect of Dietary Monascus Koji on the Liver Damage Induced by Bromobenzene in Rats (식이성 홍국이 Bromobenzene에 의한 간 손상의 해독에 미치는 영향)

  • 오정대;윤종국;유대식
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.33 no.6
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    • pp.965-972
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    • 2004
  • In the present study, it is observed that Monascus diet may have a hepatoprotective effect on the liver damage induced by bromobenzene in rats. By treatment with bromobenzene (400 mg/kg, i.p.) once a day for 3 consecutive days, the liver damage was reduced in rats fed 2% Monascus diet, based on the liver functional and histopathological findings. Furthermore, retreatment of bromobenzene to the animals with damaged liver showed higher decreasing rate of hepatic glutathione content and increasing rate of cytochrome P450 dependent aniline hydroxylase activity at 4 h in rats fed 2% Monascus diet than those fed STD diet, and V$_{max}$ in glutathione S-transferase was higher in liver of rats fed 2% Monascus diet than those fed STD diet. On the other hand, activities of antioxidant enzymes such as hepatic glutathione S-transferase, catalase and superoxide dismutase were generally higher both in bromobenzene and 2% Monascus diet treated group than those fed STD diet. In conclusion, the rats fed 2% Monascus diet showed lower liver damage than those fed STD diet, which may be due to the acceleration of bromobenzene metabolism and detoxication of oxygen free radicals.s.

Characterization of CYP125A13, the First Steroid C-27 Monooxygenase from Streptomyces peucetius ATCC27952

  • Rimal, Hemraj;Subedi, Pradeep;Kim, Ki -Hwa;Park, Hyun;Lee, Jun Hyuck;Oh, Tae-Jin
    • Journal of Microbiology and Biotechnology
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    • v.30 no.11
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    • pp.1750-1759
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    • 2020
  • The characterization of cytochrome P450 CYP125A13 from Streptomyces peucetius was conducted using cholesterol as the sole substrate. The in vitro enzymatic assay utilizing putidaredoxin and putidaredoxin reductase from Pseudomonas putida revealed that CYP125A13 bound cholesterol and hydroxylated it. The calculated KD value, catalytic conversion rates, and Km value were 56.92 ± 11.28 μM, 1.95 nmol min-1 nmol-1, and 11.3 ± 2.8 μM, respectively. Gas chromatography-mass spectrometry (GC-MS) analysis showed that carbon 27 of the cholesterol side-chain was hydroxylated, characterizing CYP125A13 as steroid C27-hydroxylase. The homology modeling and docking results also revealed the binding of cholesterol to the active site, facilitated by the hydrophobic amino acids and position of the C27-methyl group near heme. This orientation was favorable for the hydroxylation of the C27-methyl group, supporting the in vitro analysis. This was the first reported case of the hydroxylation of cholesterol at the C-27 position by Streptomyces P450. This study also established the catalytic function of CYP125A13 and provides a solid basis for further studies related to the catabolic potential of Streptomyces species.

Involvement of Kupffer Cell in $CCl_4$ induced Liver Injury: The Role of Calcium (사염화 탄소에 의한 간손상에 있어 Kupffer cell 칼슘의 역할)

  • Yang, Mie-Rha
    • The Korean Journal of Pharmacology
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    • v.32 no.1
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    • pp.75-82
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    • 1996
  • The hypothesis that calcium provoke $O_2^-$ formation by Kupffer cells and may contribute to carbon tetrachloride $(CCl_4)$ induced liver injury was studied in SD rats. In $CCl_4-treated$ animals, hepatic malonaldehyde (nmole/gm liver) and plasma ALT (IU/ml) levels elevated significantly from $119.63{\pm}13.00$ to $268.97{\pm}14.82$ and from $17.3{\pm}0.18$ to $806.08{\pm}37.63$, respectively, compared to those in controls. Activation of Kupffer cells with high dose of retinol (250,000 IU/kg/day, po, for 7 day) significantly enhanced ALT levels, while inactivation of Kupffer cells with gadolinium chloride (7.5 mg/kg/day, ip, for 2 day) attenuated the increase of serum ALT level following $CCl_4$ treatment. Diltiazem (10 mg/kg/day, ip for 2 day) given in combination with retinol led to a marked decrease in ALT levels compare to the level in rats treated only with retinol against $CCl_4$ treatment. In order to determine any alterations in cytochrome P450 activities, the P450 content and the CYP2E1 activity were measured and all $CCl_4-treated$ rats showed significantly lower levels compared to those in controls and vehicle-treated animals. There were significant increases in glutathione peroxidase in all $CCl_4-treated$ rats except diltiazem treated groups. No difference was found among untreated and vehicle-treated rats. It is concluded that Kupffer cells contribute to $CCl_4-induced$ liver injury and that calcium antagonist attenuated the increased $CCl_4-induced$ liver injury due to activation of Kupffer cells.

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Design of a 2.5Gbps Serial Data Link CMOS Transceiver (2.5Gbps 시리얼 데이터 링크 CMOS 트랜시버의 설계)

  • 이흥배;오운택;소병춘;황원석;김수원
    • Proceedings of the IEEK Conference
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    • 2003.07b
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    • pp.1185-1188
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    • 2003
  • This paper describes a design for a 2.5Gb/s serial data link CMOS transceiver based on the InfiniBand$^{TM}$ specification. The transceiver chip integrates data serializer, line driver, Tx PLL, deserializer, clock recovery, and lock detector. The designed transceiver is fabricated in a 0.25 ${\mu}{\textrm}{m}$ CMOS mixed-signal, 1-poly, 5-metal process. The first version chip occupies a 3.0mm x 3.3mm area and consumes 450mW with 2.5V supply. In 2.5 Gbps, the output jitter of transmitter measured at the point over a 1.2m, 50Ω coaxial cable is 8.811ps(rms), 68ps(p-p). In the receiver, VCO jitter is 18.5ps(rms), 130ps(p-p), the recovered data are found equivalent to the transmitted data as expected. In the design for second version chip, the proposed clock and data recovery circuit using linear phase detector can reduce jitter in the VCO of PLL.L.

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