• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.6
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• pp.1201-1206
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• 2002

In oriental medicine, human being is classified into four groups according to their body constitution status (;tae-yang, tae-eum, so-yang, and so-eum persons) considering the differences in function of internal organs and characteristics. Four body constitution, called 'sa-sang' has been recognized as an important factor for diagnosing the patients before madical teratment. Yet, the criteria to divide body constitutions or its scientific principle are not clearly defined. As an initial effort to elucidate biological priciples underlying four body constitution groups, we studied genetic variations among three constitution groups (tae-eum, so-yang, and so-eum persons). Noting distinct responses to ingested food and administered drugs among three groups, SNPs and haplotype experiments were performed in 2D6, 2C9, and 1A2 DNA regions of the cytochrome P450 gene. Significant variability in SNPs types was found in 2D6 region. Moreover, haplotyping in 2D6 region showed relatively high occurrences of haplotype 3 and 5 in so-eum person, haplotype 6 in tae-eum person, and hyplotype 1 in so-yang person. These results indicate that individuals with different body constitutions respond differently to ingested food and drugs, which might reflect constitution-specific genetic background. The genetic approach would therefore be useful to reveal intrinsic differences among four constitution body groups in the responsiveness to various drugs and external stimulations to human body.

• Journal of Life Science
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• v.34 no.3
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• pp.199-207
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• 2024

Cytochrome P450s (CYP) enzymes play a central role in the metabolism of both endogenous and xenobiotic chemical compounds. In particular, therapeutic drugs, natural products and environmental toxicants regulate expression of the tissue-specific CYP enzymes, This can cause CYP-mediated interactions among the chemical compounds such as the ingested drugs and toxicants, resulting in changes in their metabolism. This can lead to the modifications of their therapeutic and toxic effects. Intense investigations in this field throughout the last several decades have resulted in considerable progress in understanding the molecular mechanisms mediating the regulation of CYP gene expression. Now, it is well established that xenobiotic chemicals regulate the expression of specific CYP genes, and the corresponding xenobiotic-sensing receptors that mediate the expression control of specific CYP genes and their signal transduction pathways are involved in this process. This review summarizes the molecular mechanisms by which the well-known major xenobiotic-sensing receptors and other regulators affect the induction of CYP gene expression in response to exposure to various chemicals.

• Toxicological Research
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• v.26 no.1
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• pp.47-52
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• 2010

The Malassezia fungi are responsible for various human skin disorders including dandruff and seborrheic dermatitis. Of the Malassezia fungi, Malassezia globosa (M. globosa) is one of the most common in human scalp. The completed genome sequence of M. globosa contains four putative cytochrome P450 genes. To determine the roles of Malassezia P450 enzymes in the biosynthesis of ergosterol, we isolated MGL3996 gene from M. globosa chromosomal DNA by PCR. The MGL3996 gene encodes an enzyme of 616 amino acids, which shows strong similarity with known CYP52s of other species. MGL3996 gene was cloned and expressed in Pichia pastoris (P. pastoris) heterologous yeast expression system. Using the yeast microsomes expressing MGL3996 protein, a typical P450 CO-difference spectrum was shown with absorption maximum at 448 nm. SDS-PAGE analysis revealed a protein band of apparent molecular weight 69 kDa and Western blot with anti-histidine tag antibody showed that MGL3996 was successfully expressed in P. pastoris. Cloning and expression of a new P450 gene is an important step to study the P450 monooxygenase system of M. globosa and to understand the role of P450 enzymes in pathophysiology of dandruff.

• Journal of the Korean Society of Tobacco Science
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• v.11 no.1
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• pp.103-114
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• 1989

• Journal of the Korean Society of Food Science and Nutrition
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• v.30 no.5
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• pp.928-932
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• 2001

The protective effect of Hericium erinaceus methanol extract was investigated on benzo($\alpha$)pyrene(B($\alpha$)P) induced hepatotoxicity in mice, Hericium erinaceus extract was intraperitioneally injected once a hay for successive 5 days. followed by treatment with B($\alpha$)P on the fifth day. The elevated activities of serum aminotransferase and hepatic cytochrome P-450 by B($\alpha$)P was decreased by pretretament with Hericium erinaceus extract. Moreover, hepatic lipid peroxide content and glutathions S-transferase activity increased by B($\alpha$)P were significantly decrease, but depletion of glutathione content induced by B($\alpha$)P was prevented by Hericium erinaceus extract. In addition, the increased activities of superoxide diamutase, catalase and glutathions peroxidase after B($\alpha$)P-treatment were decreasd. Immunoblott analysis of hepatic microsomes showed that methanol extract of Hericium erinaceus suppressed protein level of the cytochrome P-450 1AI increaed by B($\alpha$)P. These results suggest that Hericium erinaceus extract may protect liver from damage induced by B($\alpha$)P.

• Environmental Analysis Health and Toxicology
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• v.24 no.3
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• pp.213-218
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• 2009

1-bromopropane (1-BP) has been used in numerous purposes such as an intermediate in the synthesis of pharmaceuticals, a solvent for fats, waxes, or resins and a substitute for chlorofluorocarbons that destroy the ozone layer. However, the studies related to the modulation of activities of hepatic cytochrome P450s (CYPs) are not reported yet. This study was the first study to investigate the potential effect for the activities of hepatic CYPs by the treatment of 1-BP in vivo. When 1-BP was treated to male ICR mice by dose-dependently at the dose levels of 200, 500 and 1,000 mg/kg of body weight once, the activity of CYP2E1 was selectively increased for 24 h. The inductive potency for the activity of CYP2E1 by 1-BP was equal to induction by acetone a well-known selective CYP2E1 inducer. The present results indicated that 1-BP would affect the metabolism of 1-BP itself and/or other xenobiotics.

• Mass Spectrometry Letters
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• v.3 no.4
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• pp.104-107
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• 2012

Mollugin isolated from Rubia cordifolia is known to have anti-inflammatory, anti-cancer, and anti-viral activities. In the present study, a cocktail probe assay and LC-MS/MS were used to investigate the modulating effect of mollugin on cytochrome P450 (CYP) enzymes in male ICR mice. After mollugin was orally administrated to mice at the 20, 40, or 80 mg/kg for 3 days, the activities of CYP in hepatic S-9 fractions were investigated. Unlike the selective inhibitory effect of mollugin on CYP1A2-catalyzed phenacetin O-deethylation in vitro, mollugin only significantly inhibited the activity of CYP2E1-catalyzed chlorzoxazone 6-hydroxylase in vivo. The activities of other CYPs were only slightly altered by mollugin. The results of this study suggest that mollugin might cause herb-drug interactions via the selective inhibition of CYP2E1 in vivo.

• Journal of Microbiology and Biotechnology
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• v.20 no.4
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• pp.712-717
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• 2010

Cytochrome P450 enzymes (P450s) are involved in the synthesis of a wide variety of valuable products and in the degradation of numerous toxic compounds. The P450 BM3 (CYP102A1) from Bacillus megaterium was the first P450 discovered to be fused to its redox partner, a mammalian-like diflavin reductase. Here, we report the development of a whole-cell biocatalyst using ice-nucleation protein (Inp) from Pseudomonas syringae to display a hemeand diflavin-containing oxidoreductase, P450 BM3 (a single, 119-kDa polypeptide with domains of both an oxygenase and a reductase) on the surface of Escherichia coli. The surface localization and functionality of the fusion protein containing P450 BM3 were verified by flow cytometry and measurement of enzymatic activities. The results of this study comprise the first report of microbial cell-surface display of a heme- and diflavin-containing enzyme. This system should allow us to select and develop oxidoreductases containing heme and/or flavins into practically useful whole-cell biocatalysts for extensive biotechnological applications, including selective synthesis of new chemicals and pharmaceuticals, bioconversion, bioremediation, live vaccine development, and biochip development.

• Journal of Animal Science and Technology
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• v.46 no.3
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• pp.315-324
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• 2004

Cytochrome P450 aromatase is the enzyme responsible for biosynthesis of female sex hormone(estrogen) and 19-nortestosterone(nandrolone), a unique steroid hormone endogenously synthesized in the pig. By use of RT-PCR coupled with DHPLC technique (WAVE analysis), expression pattern of isoforms of porcine cytochrome P450 aromatase gene was investigated. Relatively higher expression of aromatase mRNA was observed in testis than in ovary and this result accounted for the previous findings of higher blood estrogen level in male compared with female in this species. The result from the DHPLC demonstrated that PCR amplified DNA fragments of ovary and testis tissues. using unique PCR primers for all three types of aromatase genes, were different from those of type II and ill genes. Further nucleotide sequence analyses of the plasmid clones containing the PCR products revealed that nucleotide sequences of all clones were identical to type I aromatase gene(ovary type). Thus, the result from the present study indicates that the ovary and testis express the same type of aromatase gene. Therefore, the efficacy of DHPLC techniques used for this study helped us to analyze tissue-specific expression of isoform of genes containing the nucleotide sequences with high homology.

• Archives of Pharmacal Research
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• v.22 no.2
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• pp.99-107
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• 1999

A series of organosulfur compounds were synthesized with the aim of developing chemopreventive compounds active against hepatotoxicity and chemical carcinogesis. 2-(Allylthio) prazine (2-AP) was effective in inhibiting cytochrome P450 2E1-mediated catalytic activities and protein expression, and in inducing microsomal epoxide hydrolase and major glutathione S-transferases. 2-AP reduced the hepatotoxicity caused by toxicant sand elevated cellular GSH content. Development of skin tumors, pulmonary adenoma and aberrant crypt foci in colon by various chemical carcinogens was inhibited by 2-AP pretreatment. Anticarcinogenic effects of 2-AP at the stage of initiation of tumors were also observed in the aflatoxin B1 ($AFB_1$)-induced three-step medium-term hepatocarcinogenesis model. Reduction of $AFB_1$-DNA adduct by 2-AP appeared to result from the decreased formation of $AFB_1$-8,9-epoxide via suppression of cytochrome P450, while induction of GST 2-AP increases the excretion of glutathione-conjugated $AFB_1$ . 2-AP was a radioprotective agent effective against the lethal dose of total body irradiation and reduced radiation-induced injury in association with the elevation of detoxifying gene expression. 2-AP produces reactive oxygen species in vivo, which is not mediated with the thiol-dependent production of oxidants and that NF-KB activation is not involved in the induction of the detoxifying enzymes. the mechanism of chemoprotection by 2-AP may involve inhibition of the P450-mediated metabolic activation of chemical carcinogens and enhancement of electrophilic detoxification through induction of phase II detoxification enzymes which would facilitate the clearance of activated metabolites through conjugation reaction.