• Environmental Mutagens and Carcinogens
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• v.17 no.2
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• pp.97-108
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• 1997

The drugs or xenobiotics introduced to the body, are detoxified through the process of biotransformation in the body. In this process, most of the insoluble compounds become more polar, soluble and easily excretable. But, parts of introduced materials are metabolized to highly reactive electrophilic carcinogens through activation pathways. These metabolites are toxic and can react with DNA, RNA and proteins which are nucleophilic compounds. The objective of this study is to illustrate the aleactivation pathways of two highly reactive epoxide compounds, vinyl carbamate epoxide (VCO) and 2'-(4-nitrophenoxy)oxirane (NPO). They are the ultimate electrophilic carcinogens of ethyl carbamate(urethane) and 4-nitrophenyl vinyl ether, respectively. In this research, we studied the inhibition of the mutagenic activities of VCO or NPO by nuchieophiles [glutahione(GSH) and N-acetylcysteine(NAC)], detoxifying enzymes[epoxide hydrolase and glutathione-S-transferase(GST)] and intracellular organelles (microsomes and cytosol). In addition we also tested the suppression of DNA adducts formation by GSH and NAC. The results are summerized as follow. 1. The microsomes and cytosol which contain epoxide hydrolase and GST, respectively, decreased the mutagenicity of VCO (74% and 95%, respecfivel), and NPO (35% and 93%, respectively). The nucleophilic GSH and NAC decreased the mutagenicity by 86% (VCO) and 80% (NPO), 76% (VCO) and 40% (NPO), respectively. 2. The purified epoxide hydrolase decreased the mutagenicity of two epoxides in a dose-dependent manner, and GSH also decreased the mutagenicity in the presence of GST. 3. Formation of two DNA adducts, 7-(2'-oxoethyi)guanine (OEG) and N2,3-ethenoguanine(EG), were compared in the presence of calf thymus DNA and epoxide (VCO or NPO) in vitro system. The amounts of DNA adducts were decreased in the presence of GSH (25% and 29% in VCO, 32% and 29% in NPO), and NAC (14% and 16% in VCO, 21% and 11% in NPO), respectively. From these results, it is concluded that the ultimate carcinogenic metabolites, VCO and NPO, can be made in the body, but much of them may be inactivated and detoxified by the nucleophilic GSH, NAC and detoxifying enzymes (epoxide hydrolase and GST). Therefore, by these mechanism, the formation of DNA adducts and mutagenic activities of these two epoxides may be lowered in vivo.

• Journal of Life Science
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• v.18 no.8
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• pp.1059-1065
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• 2008

KIF21A is a member of the Kinesin superfamily proteins (KIFs), which are microtubule-dependent molecular motors, anterograde axonal transporters of cargoes. Recently, congenital fibrosis of the extraocular muscles 1 (CFEOM1) has been shown to result from a small number of recurrent heterozygous missense mutations of KIF21A. CFEOM1 results from the inability of mutated KIF21A to successfully deliver cargoes to the development of the occulo-motor neuron or neuromuscular junction. Here, we used an yeast two-hybrid system to identify a protein that interacts with the WD-40 repeat domain of KIF21A and found a specific interaction with Purkinje cell protein-2 (Pcp-2), a small protein also known as L7. Pcp-2 protein bound to the WD-40 domain of KIF21A and KIF21B but not to other KIFs in yeast two-hybrid assays. In addition, this specific interaction was also observed in the glutathione S-transferase pull-down assay. An antibody to Pcp-2 specifically co-immunoprecipitated KIF21A associated with Pcp-2 from mouse brain extracts. These results suggest that Pcp-2 may be involved in the KIF21A-mediated transport as a KIF21A adaptor protein.

• Korean Journal of Medicinal Crop Science
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• v.8 no.1
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• pp.21-28
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• 2000

The biological activities of water, ethanol and 50% ethanol extracts from Acanthopanax root bark were compared. 94% of Hep3B cell growth was inhibited by adding 1.0g/L of 50% ethanol extracts from A. senticosus root bark. It was also showed that above 90% of A549 cell growth was inhibited by adding 1.0g/L of 50% ethanol extracts. The 50% ethanol extracts of A. sessiliflorum root bark showed that the extracts selectivity were from 1.5 to 3.4 by adding all samples. For screening immunomodulating activities, Jurkat(T-cell) was showed that the cell growth and viability were more increased and activited 275% by adding the 50% ethanol extracts from A. senticosus root bark. The result of anti-mutagenicity of 50% ethanol extracts of A. senticosus root bark was most effective than any other samples. The enhancement of glutathione-S-transferase activity was increased 241% by adding 1.0g/L 1 : 1 extracts of A. senticosus root bark. 72% of oxidation was inhibited by adding 1.0g/L of 50% ethanol extracts from A. senticosus root bark.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.5
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• pp.796-801
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• 2002

To investigate the effects of Ewomia ulmoides olivon extract on the serum and hepatic lipid status and anti-oxidant enzyme activities, male Sprague Dawley (SD) rats were given high fat diets and Eucomia ulmoides olivon ethanol extracts for 6 weeks. Rats were divided into (our groups consisting the control (C), Eucomia ulmoides oliuon extract fed group (CE), high fat diet group (CL) and the extract and high fat fed group (CLE). Eucomia ulmoides oliuon ethanol extract lowered total cholesterol, but increased HDL-cholesterol and HDL-cholesterol/total cholesterol of the serum compared to the control. On the other hand, the ratio of HDL-cholesterol/total cho-lcsterol (HTR) was increased by 55% (p<0.05). High fat diet significantly increased serum cholesterol contents, but decreased HDL-cholesterol level and HTR (p<0.05). Atherogenic index (AI) of CL group was increased by almost four times of the control (p<0.05). Triglycerides (TG) and phospholipids were also increased by high fat diet. Eucomia ulmoides oliuon ethanol extract decreased the levels of TG (p<0.05) and phospholipids (p<0.05). Although liver antioxidant engyme activities including glutathione sulfur transferase (GST), superoxide dismutase (SOD) and catalase were decreased by high fat diet, those were stimulated by the administration of Eucommia ulmoides olivon ethanol extract.

• Journal of Life Science
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• v.19 no.2
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• pp.228-233
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• 2009

The purpose of this study is to evaluate the activities of five different antioxidant enzymes in various tissues of Papilio xuthus during pupal stage. Superoxide dismutase (SOD) activity in haemolymph was the highest just after pupation and then decreased gradually until 7 days after pupation but the activity in other tissue was constant during metamorphosis. This result indicates that primary antioxidant process of reactive oxygen species proceed in haemolymph. Catalase (CAT) activity in studied tissues was also the highest just after pupation and its relative activity was also high during pupal stage, suggesting that CAT is the primary enzyme in catalysis of hydrogen peroxide. Glutathion peroxidase (GPX) activity was constant and its relative activity was very low in all tested tissues. Glutathione S-transferase (GST) activity in haemolymph was high at 3 days and 5 days after pupation, and the activity in fat body was the highest at the 1 day after pupation and then decreased gradually for 7 days after pupation. Glutathion reductase (GR) activity in haemolymph and fat body was high at 1 day after pupation, but relatively low GR activity was detected in the rest tissues. Based on these results, GST activity was higher than that of GPX and GR, and it is also believed that GST was more involved in reduction process through lipid peroxidation than GPX.

• Journal of Food Hygiene and Safety
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• v.16 no.4
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• pp.349-354
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• 2001

Oxidative stress is believed to play an important role in the development of vascular complications associated with diabetes mellitus. We examined the antioxidative effect of sesamin and sesamolin on the preventing the development of insulin dependent diabetes mellitus using streptozotocin-induced Spraque Dawley diabetic rats. From 48 hours after injection of streptozotocin (60 mg/kg body weight), a portion of diabetic rats were fed with 0.2% sesamin and sesamolin containing diet for 3 weeks. There were significant differences of blood glucose and kidney weight between diabetic ports and control. Sesamin and sesamolin increased glutathione-S-transferase activity in kidney. The concentration of the thiobarbituric acid-reactive substances in the serum, liver, and kidney of diabetic rats administered sesamin and sesamolin decreased significantly as compared with that of the non-treated diabetic group. Dietary sesamin and sesamolin suppressed the oxidative stress in the diabetic rats. These results demonstrated that sesamin and sesamolin are potential and effective antioxidants that can protect the complications associated with diabetes.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.1041-1054
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• 2004

Electroacupuncture (EA) has been reported to increase pain threshold, and to enhance the NK cell activity by up-regulation of IFN-γ and endogenous β-endolphin. For the purpose of understanding the molecular mechanism of EA stimulation, we analyzed the gene expression profile of rat hypothalamus, treated on Zusanli (ST36) with EA, in comparison with control group by oligonucleotide chip microarray (Affymetrix GeneChip Rat Neurobiology U34 Array) and real-time RT-PCR. Sprague-Dawley (S-D) male rats were stimulated at the Zusanli (ST36) acupoint in restriction holder. Simultaneously the control group was given only holder stress without EA stimulation. In order to prove the appropriateness of EA treatment, we measured spleen NK cell activity with standard 51Cr release assay. NK cell activity of EA group was significantly increased comparing to control group. The microarray and PCR results show that EA treatment up-regulates expression of genes associated with 1) nerve growth such as NGF induced factor A and VGF, 2) signal transduction such as 5HT3 receptor subunit, AMPA receptor binding protein and Na-dependent neurotransmitter transporter, and 3) anti-oxidation such as superoxide dismutase and glutathione S-transferase. In addition, the activity of the anti-oxidative enzyme, SOD of hypothalamus, liver and RBC was enhanced compared to that of control. The list of differentially expressed genes may implicate further insight on the mechanism of acupuncture effects.

• Nutrition Research and Practice
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• v.4 no.2
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• pp.93-98
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• 2010

Our previous study demonstrated that methanolic extract of Chrysanthemum zawadskii Herbich var. latilobum Kitamura (Compositae) has the potential to induce detoxifying enzymes such as NAD(P)H:(quinone acceptor) oxidoreductase 1 (EC 1.6.99.2) (NQO1, QR) and glutathione S-transferase (GST). In this study we further fractionated methanolic extract of Chrysanthemum zawadskii and investigated the detoxifying enzyme-inducing potential of each fraction. The fraction (CZ-6) shown the highest QR-inducing activity was found to contain (+)-(3S,4S,5R,8S)-(E)-8-acetoxy-4-hydroxy-3-isovaleroyloxy-2-(hexa-2,4-diynyliden)-1,6-dioxaspiro [4,5] decane and increased QR enzyme activity in a dose-dependent manner. Furthermore, CZ-6 fraction caused a dose-dependent enhancement of luciferase activity in HepG2-C8 cells generated by stably transfecting antioxidant response element-luciferase gene construct, suggesting that it induces antioxidant/detoxifying enzymes through antioxidant response element (ARE)-mediated transcriptional activation of the relevant genes. Although CZ-6 fraction failed to induce hepatic QR in mice over the control, it restored QR activity suppressed by $CCl_4$ treatment to the control level. Hepatic injury induced by $CCl_4$ was also slightly protected by pretreatment with CZ-6. In conclusion, although CZ-6 fractionated from methanolic extract of Chrysanthemum zawadskii did not cause a significant QR induction in mice organs such as liver, kidney, and stomach, it showed protective effect from liver damage caused by $CCl_4$.

• Parasites, Hosts and Diseases
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• v.56 no.2
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• pp.135-145
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• 2018

Due to the critical location and physiological activities of the retinal pigment epithelial (RPE) cell, it is constantly subjected to contact with various infectious agents and inflammatory mediators. However, little is known about the signaling events in RPE involved in Toxoplasma gondii infection and development. The aim of the study is to screen the host mRNA transcriptional change of 3 inflammation-related gene categories, PI3K/Akt pathway regulatory components, blood vessel development factors and ROS regulators, to prove that PI3K/Akt or mTOR signaling pathway play an essential role in regulating the selected inflammation-related genes. The selected genes include PH domain and leucine- rich-repeat protein phosphatases (PHLPP), casein kinase2 (CK2), vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), glutamate-cysteine ligase (GCL), glutathione S-transferase (GST), and NAD(P)H: quinone oxidoreductase (NQO1). Using reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), we found that T. gondii up-regulates PHLPP2, $CK2{\beta}$, VEGF, GCL, GST and NQO1 gene expression levels, but down-regulates PHLPP1 and PEDF mRNA transcription levels. PI3K inhibition and mTOR inhibition by specific inhibitors showed that most of these host gene expression patterns were due to activation of PI3K/Akt or mTOR pathways with some exceptional cases. Taken together, our results reveal a new molecular mechanism of these gene expression change dependent on PI3K/Akt or mTOR pathways and highlight more systematical insight of how an intracellular T. gondii can manipulate host genes to avoid host defense.

• Journal of Society of Preventive Korean Medicine
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• v.3 no.2
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• pp.183-210
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• 1999

In order to investigate the protective effect of Injinhotanghapsihosogantang-gagambang on the liver injury of rats induced by $CCl_4$ and d-galactosamine, the serum transaminase(GOT&GPT) alkaline phosphatase(ALP), lactic dehydrogenase(LDH) for enzyme activities, triglyceride for serum component, liver weight and glutathione S-transferase(GST), Superoxide dimutase(SOD) were measured. All animals were divided into 5 groups, those were normal group(untreated), control group(treated with vehicle 0.9% Saline solution), sample I group(10mg/kg administrated), sample II group(30mg/kg administrated), Silymarin 200 administrated group. The results were as follows: 1. The inhibitory effects of the serum GOT activities in rats induced by $CCl_4$ were noted in both sample I (p<0.001) and sample II group(p<0.001). In serum GPT activities, sample I (p<0.01) and sample II group(p<0.01). 2. The inhibitory effects of the serum LDH activities in rats induced by $CCl_4$ were noted in both sample I (p<0.001) and sample II group(p<0.001). 3. The increased effects of the serum ALP activities in rats induced by $CCl_4$ were not recognized. 4. The inhibitory effects of the serum triglyceride content level in rats induced by $CCl_4$ were inhibited in only sample II group(p<0.05). 5. The increased effects of the liver weight level in rats induced by $CCl_4$ were inhibited in both sample I (p<0.05) and sample II group(p<0.05). 6. The inhibitory effects of the GST activities in rats induced by $CCl_4$ were not recognized. In SOD activities, both sample I (p<0.05) and sample II group(p<0.001) showed the inthbitory effects. 7. The inhibitory effects of in the serum GOT, GPT activities in rats induced by d-galactosamine were not recognized. 8. The increases of the serum LDH level in rats induced by d-galactosamine were noted in both sample I (p<0.01) and sample II group(p<0.001). 9. The inhibitory of the serum triglyceride content level in rats induced d-galactosamine were noted in only sample II group(p<0.05). According to the above results, it is considered that Injinhotanghapsihosogantang-gagambang has protective effect against liver injury in rats induced by $CCl_4$ and d-galactosamine.