• The Korean Journal of Pharmacology
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• v.32 no.2
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• pp.233-241
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• 1996

Previous studies have shown that glucocorticoid suppresses microsomal epoxide hydrolase(EH) gene expression and that EH expression is altered during pregnancy. The effects of progesterone on the expression of rat EH and certain glutathione S-transferase(GST) genes were examined in this study. Northern RNA blot analysis revealed that progesterone was effective in increasing hepatic EH mRNA levels at 12 h to 48 h after treatment with a maximal 9-fold increase being noted at 12 h time point. Nonetheless, multiple daily treatment with progesterone rather caused minimal relative increases in EH mRNA levels. GST Ya and Yb1/2 mRNA levels were also transiently elevated at 12 h after progesterone treatment, followed by gradual decreases from the maximal Increases at day 1, 2 and 5 post-treatment. These changes in EH and GST mRNA levels were noted only at a relatively high dose of progesterone. Furthermore, immunoblot analyses showed that rats treated with progesterone for 5 days failed to show EH or GST induction, indicating that progesterone-induced alterations in EH and GST mRNA levels do not reflect bona fide induction of the detoxifying enzymes. Concomitant progesterone treatment of rats with the known EH inducers including ketoconazole and clotrimazole failed to additively nor antagonistically alter EH mRNA levels. In contrast, dexamethasone substantially reduced ketoconazole- or clotrimazole-inducible EH expression. These results showed that progesterone stimulates the EH, GST Ya and Yb1/2 gene expression at early times followed by marked reduction in the RNA levels from the maximum after multiple treatment and that the changes in mRNA do not necessarily reflect induction of the proteins.

• The Korean Journal of Pesticide Science
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• v.7 no.1
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• pp.38-44
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• 2003

In vitro inhibitory activity of 34 insecticides and 31 fungicides to glutathione-S-transferase and esterases extracted from rats was determined. Of tested pesticides, the pesticides with high activity on both detoxifying enzymes were mixed with pesticides that are known to be detoxified by detoxifying enzymes. Glutathione-S-transferase was inhibited by thiodicarb $(I_{50}:1.87\times10^{-4}M)$, thiocyclam $(7.40\times10^{-4}M)$, dithianon $(7.55\times10^{-5}M)$, and tolylfluanide $(8.66\times10^{-5}M)$, while esterases by dichlorvos $(8.95\times10^{-8}M)$, pirimicarb $(2.74\times10^{-6}M)$, pyrazophos $(3.31\times10^{-5}M)$, and benomyl $(4.96\times10^{-5}M)$. After acephate known to be detoxified by glutathione-S-transferase was mixed with glutathione-S-transferase-inhibiting pesticides and phenthoate known to be detoxified by esterases was mixed with esterases-inhibiting pesticides, insecticidal activities of such mixtures were determined against diamondback moth (PlutelLa xylostella L.). Synergistic action was observed in all pesticide combinations. The highest synergistic action was obtained when phenthoate was combined with dichlorvos, showing that co-toxicity coefficients were 1512 and 1877 after 24 and 48 hours of treatment, respectively. Several other combinations of pesticides, such as phenthoate with benomyl, and acephate with dithianon, also showed synergism, showing that their co-toxicity coefficients were about 1,000 and 500, after 24 hours of treatment, respectively. Our results showed that combinations of pesticides inhibited by detoxifying enzymes and ones detoxified by detoxifying enzymes resulted in increased toxicities of pesticides, suggesting that such combinations could be used to develop pesticide mixtures with more broad spectrum and high effectiveness.

• Korean Journal of Pharmacognosy
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• v.30 no.1
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• pp.12-17
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• 1999

The youngkaechulgamtang (Y) composed of four herb drugs, including Hoelen (H). Cinnamomi Ramulus (C). Atractylodis Rhizoma Alba (A) and Glycyrrhizae Radix (G). In oriental medicine literatures, Youngkaechulgamtang is described to be effective in headache, inflammation, uremia, gastritis, diarrhea and hypertension. To estimate the clinical effectiveness of Youngkaechulgamtang, several pharmacological experiments were carried out. The results are summerized as follows; On acetaminophen-induced hepatotoxicity, C+A, Y-G, Y-H, MIX and Y showed the significant elevation of glutathione-S-transferase. But, C+A, Y-G, Y-H, MIX and Y showed the significant suppression of serum aminotransferases. On ANIT-induced cholestasis, U (Ursodesoxycholic acid 50 mg/kg)+$Y_l$ (760 mg/kg) showed the significant increase of bile juice volume. $Y_l,\;Y_2$ (1520 mg/kg), U, $U+Y_l$ showed the remarkable increase of cholic acid. U and $U+Y_l$ showed the significant decrease of total bilirubin. From these results, it is suggest that Y shows liver protective effect against various hepatic injury. Especially, Youngkaechulgamtang was more effective than mixture of 4 ingredients in the elevation of glutathione-S-transferase in acetaminophen-induced hepatotoxicity.

• Microbiology and Biotechnology Letters
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• v.17 no.2
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• pp.148-153
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• 1989

A strain of alkalophilic Bacillus sp. YC-335 has been isolated from soil. The strain was capable of producing large amount of cyclodextrin glycosyl transferase (CGTase) in the culture broth. The preferable medium composition has been determined to be as follows : 1.5% soluble starch, 5% corn steep liquor, 0.1% $K_2$HPO$_4$, 0.02%mgSO$_4$.7$H_2O$, 1% CaCO$_3$and 1% Na$_2$CO$_3$(pH 10.3). The highest enzyme production was observed after 48 hours of cultivation at 31$^{\circ}C$. The optimum pH and temperature for the activity of crude enzyme were 6.0 and 5$0^{\circ}C$, respectively. The enzyme was stable between pH 5 and 9, and upto 5$0^{\circ}C$. The enzyme converted starch into $\alpha$-, $\beta$- and ${\gamma}$-CD in the relative amounts of 1:10:1.5, respectively.

• Bulletin of the Korean Chemical Society
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• v.24 no.8
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• pp.1188-1192
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• 2003

In order to study the role of residue in the active site of glutathione S-transferase (GST), Tyr 108 residue in human GST P1-1 was replaced with alanine, phenylalanine and tryptophan by site-directed mutagenesis to obtain mutants Y108A, Y108F and Y108W. These three mutant enzymes were expressed in Escherichia coli and purified to electrophoretic homogeneity by affinity chromatography on immobilized GSH. The substitutions of Tyr108 significantly affected $K_m^{CDNB}$ and $K_m^{ETA}$, whereas scarcely affected $K_m^{GSH}$. The substitutions of Tyr108 also significantly affected $I_{50}$ of ETA, an electrophilic substrate-like compound. The effect of these substitutions on kinetic parameters and the response to inhibition suggests that tyrosine 108 in hGST P1-1 contributes to the binding of the electrophilic substrate and a major determinant in the binding of CDNB is the aromatic ring of Tyr108, not its hydroxyl group.

• Current Research on Agriculture and Life Sciences
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• v.28
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• pp.63-68
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• 2010

The epigenetic therapy of cancers is emerging as an effective and valuable approach to both chemotherapy and the chemoprevention of cancer. The utilization of epigenetic targets that include histone methyltransferase (HMTase), Histone deacetylatase, and DNA methyltransferase, are emerging as key therapeutic targets. SET containing proteins such as the HMTase Setd1b has been found significantly amplified in cancerous cells. In order to shed some light on the histone methyl transferase family, we cloned the Setd1b gene from Mus musculus and build a collection of vectors for recombinant protein expression in E.coli that will pave the way for further structural biology studies. We prospect the role of the Setd1b pathway in cancer therapy and detail its unique value for designing novel anti-cancer epigenetic-drugs.

• Korean Journal of Pharmacognosy
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• v.34 no.1 s.132
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• pp.91-99
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• 2003

Ras proteins play an important role in intracellular signal transduction pathways involved in cell growth and the mutated twas genes have been found in thirty percent of human cancers. Ras proteins (H-, K- and N-Ras) are small guanine nucleotide binding proteins that undergo a series of posttranslational modifications including the farnesylation onto cysteine 186 at C-terminal of Ras by farnesyl protein transferase (FPTase). This is a mandatory process for retention of transforming ability. Therefore, inhibitors of FPTase have a promising to be effective antitumor agents. In our screening program for FPTase inhibitors, the methanol extracts of 193 plants were screened for the inhibitory activity against FPTase partially purified from the rat brain. Extracts of 7species plants including Areca catechu, Saururus chinensis, Curcuma longa, Artemisa princeps, Paeonia suffruticosa, Spatholobus suberectus, Cinnamomum cassia, Cinnamomum japonicum inhibited more than 60% of FPTase activity at a concentration of $100\;{\mu}g/ml$.

• Korean Journal of Medicinal Crop Science
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• v.16 no.6
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• pp.427-433
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• 2008

This study was performed to investigate antioxidant activities and glutathione S-transferase (GST) activity according to parts of the Acer mono and A. okamotoanum. Most extracts showed high scavenging activities on DPPH. Especially, the bark of A. okamotoanum showed higher activity as 98.4% than the control, BHA as 96.5%. A. mono and A. okamotoanum showed high ability on nitrite scavenging, but decreasing tendency according to decreasing of pH. On SOD-like test, the wood of A. okamotoanum showed highest activity as 35.4% at 1.0mg/ml concentration. Also, the extracts obtained high activity on GST test. Therefore, the water extracts from the bark of A. mono and A. okamotoanum have relatively good antioxidant activity and GST activity. Especially, the bark of A. okamotoanum showed the highest activity on all of extracts, could be the use of functional foods and biomaterials.

• Bulletin of the Korean Chemical Society
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• v.26 no.3
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• pp.433-439
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• 2005

To gain further insight on the relationship between structure and functions of glutathione S-transferase (GST), the three tyrosine 108 mutants, Y108A, Y108F, and Y108W, of human GST P1-1 were expressed in Escherichia coli and purified to electrophoretic homogeneity by affinity chromatography on immobilized GSH. The substitution of Tyr 108 with alanine resulted in significant decrease of the GSH-conjugation activity and the GSH peroxidase activity, but approximately 63% increase of steroid isomerase activity toward ${\Delta}^5$–[androstene 3,17-dione. On the other hand, the substitution of Tyr 108 with phenylalanine resulted in decreases of $k_{cat}\;and\;k_{cat}/K_m{^{EPNP}}$ by 2 orders of magnitude, suggesting that Tyr 108 residue of hGSTP1-1 are considered to be important for the catalysis and the binding of the epoxide substrates. The substitution of Tyr 108 with tryptophan resulted in significant decreases of the specific activities toward EPNP, cumene hydroperoxide and ${\Delta}^5$–ndrostene 3,17-dione, but approximately 2-fold increase on the enzyme-catalyzed addition of GSH to DCNB. We conclude from these results that Tyr 108 in hGST P1-1 plays very different roles depending upon the nature of the electrophilic substrates.

• Asian-Australasian Journal of Animal Sciences
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• v.19 no.9
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• pp.1354-1360
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• 2006

Maize-soybean meal diets with 0, 100, 200 and 300 g/kg double zero rapeseed meal ('00' RSM) with and without an enzyme mixture (xylanase, pectinase, cellulase) at a level of 1.6 g/kg were evaluated with 624 day-old broiler chicks for 5 weeks. The birds were randomly allocated to eight dietary treatments with three replicates of 26 birds each. Average daily gain (ADG) and feed intake (FI) were recorded weekly and ileal viscosity, organ weights, serum enzyme activity, hormonal profile and hematological parameters were measured at the end of week 5. Average daily gain during the weekly periods was significantly influenced by the dietary level of '00'RSM (p<0.01). Inclusion of '00' RSM improved the ADG up to day 28 with the increased level; beyond that time no improvement was recorded when compared to control groups. However, ADG from 1-35 days was significantly different between 300 g/kg inclusion level of '00' RSM and the control diet. Inconsistent decline in feed intake and feed conversion ratio was observed up to day 21 and the trend was reversed thereafter. The proportion of '00' RSM in the diet had a significant ($p{\leq}0.05$) influence on thyroid weight but had no effect on the relative weights of liver and heart, serum enzyme activities (${\gamma}$-glutamyl transferase, alanine amino transferase and aspartate amino transferase), thyroid hormones ($T_3$ and $T_4$), hemoglobin level and hematocrit. Significant improvement in ADG was recorded during the 2nd week of age with the addition of enzyme, whereas for all other periods, including the whole period of the trial, higher but non-significant ADG was observed. FI and FCR were not affected by the addition of enzyme but there was a numerical reduction in FCR during the whole period. The addition of enzyme reduced the ileal viscosity at all levels of '00' RSM inclusion. The results suggest that '00' RSM can be included up to 300 g/kg in broiler diets without any adverse effects on health and performance. The addition of commercial enzyme mixture containing xylanase, pectinase, cellulase to broiler diets containing '00'RSM has some effect on growth rate and feed conversion efficiency.