• Title/Summary/Keyword: Glutathione-S-transferase (GST)

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Differential Effects of Nongenotoxic and Genotoxic Carcinogens on the Preneoplastic Lesions in the gat Liver

  • Kim, Dae-Joong;Lee, Kook-Kyung;Hong, Jin-Tae
    • Archives of Pharmacal Research
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    • v.21 no.4
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    • pp.363-369
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    • 1998
  • Glutathione S-transferase placental form (GST-P) positive foci development and its expression in liver exposed by nongenotoxic carcinogens phenobarbital (PB) and clofibrate (CF), and genotoxic carcinogen 2-amino-3-methylimidazo[4,5-f] quinoline (IQ) were investigated as a measure of carcinogenic potential of these chemicals. Male F344 rats were initially given a single intraperitioneal injection of diethyinitrosamine (200 mg/kg), and 2 weeks later, animals were fed diets containing 0.03% IQ or 0.5% CF or 0.05% PB or basal diet as a control for 6 weeks. All rats were subjected to two-thirds partial hepatectomy (PH) at week 3. Sequential sacrifice of rats was performed at 8 weeks or 52 weeks, and liver tissues were examined for immunohistochemical staining of GST-P positive foci. The numbers (No./$cm^2$) and areas ($mm^2$/ $cm^2$) of GST-P positive foci were increased by IQ or PB, but were decreased by CF compare to the control. Consistent with the development of GST-P positive foci, a time-related increase in the expression of GST-P mRNA was found in the rats treated with IQ, whereas CF decreased it. The incidence of hepatocellular carcinoma at 52 weeks was increased by all three chemicals. These results show that PB and IQ induced GST-P positive foci, but the peroxisome proliferator CF did not, which suggest that the prediction of carcinogenic potency based on the development of prenoplastic foci may cause false negative in a particular category compounds like peroxisome proliferators.

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The Potential of Cnidium officinale Makino as the Component of Gamgungtang to Induce the phase II Enzyme in vivo (감궁탕 처방 중 천궁의 생체에서 Phase II 효소 유도 효과)

  • Han Sang-Hun;Shon Yun-Hee;Kim Hyuck;Lee Hee-Soon;Park In-Kyung;Nam Kyung-Soo;Kim Cheorl-Ho;Lim Jong-Kook
    • Korean Journal of Acupuncture
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    • v.20 no.1
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    • pp.65-70
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    • 2003
  • The activity of phase II enzyme in the liver of mice was examined following the application of Cnidium officinale Makino aqua-acupuncture solution (COMAS). The application of COMAS $CV_{12}$ to mice for 7 days increased quinone reductase(QR) activity. The glutathione S-transferase(GST) activity was also increased with COMAS. A greater increase was observed in the glutathione(GSH) levels than in the QR and GST activities.

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Characteristics of resistance to chlorpyrifos in diamondback moth(Plutella xylostella L.) collected from Chinese cabbage alpine farmland at Gangwon-do, Korea (강원도 고랭지 Chlorpyrifos 포장저항성 배추좀나방(Plutella xylostella L.)의 저항성 특성)

  • Cho, Jun-Mo;Kim, Kyung-Joo;Kim, Seong-Soo;Park, Hong-Ryeol;Lim, Chun-Keun;Hur, Jang-Hyun
    • The Korean Journal of Pesticide Science
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    • v.10 no.1
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    • pp.50-55
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    • 2006
  • A field-resistant strain of the diamondback-moth(Plutella xylostella L.), collected from Chinese cabbage alpine farmland at Gangwon-do, Korea, was used for determination of the characteristics of resistance to chlorpyrifos using the activities of esterases and glutathione-S-transferase(GST), protein sequestration and AChE insenstivity. Although the activities of esterases extracted from resistant strain and susceptible strain were not significantly different, isozyme bands shown on the electrophoresis were different. GST activity from field resistant strain was 1.5-fold higher than that of susceptible. No differences were shown between resistant and susceptible ones in protein sequestration. The insensitivities of AChE to chlorpyrifos, however, extracted from susceptible strain was 460-fold higher than those of resistant. These results indicated that the insensitivity of AChE is the major factor for developing the resistance and activities of GST might be a minor factor.

The Anticancer Effects of Doenjang Made with Various Kinds of Salt (소금 종류를 달리하여 제조한 된장에서의 항암효과)

  • Lee, Kyeoung-Im;Park, Kun-Young;Ahn, Hyung-Ki
    • Culinary science and hospitality research
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    • v.17 no.5
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    • pp.241-252
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    • 2011
  • The study was carried out to evaluate the anticancer effects in Korean soybean paste(doenjang) added with sun-dried salt(S-D), roasted salt(R-D), bamboo salt roasted once(B1-D) or bamboo salt roasted nine times(B9-D). In MTT assay, S-D, R-D, B1-D and B9-D exhibited a significant inhibitory activity(64-87% and 68-92%) against the proliferation of AGS human gastric adenocarcinoma cells by adding 0.05% and 0.1% of methanol extract. Among Balb/c mice injected with sarcoma-180 cells, the bodies, livers, spleens, kidneys and heart weight of the mice administered with 4 kinds of doenjang extracts were heavier than the non-administered ones of the group. However, no difference was found between the control and doenjang administered groups. Four kinds of doenjang inhibited significantly the tumor growth, especially R-D and B1-D showing an inhibition of tumor cell growth up to 97% by the administration of 1.0 mg/kg methanol extracts of doenjang. The activity of natural killer(NK) cells was relatively high in mice administered with four kinds of doenjang. Particularly, mice administered with R-D methanol extract showed a stronger activity of 88.2%. The activity of glutathione S-transferase(GST) in mice administered with four kinds of doenjang was higher than that of the non-administered group. In particular, the GST activity was the strongest in the group with B1-D. As these results indicate the various kinds of salt have different effects on the anticancer activity of doenjang.

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Chemopreventive Potential of Salvia miltiorrhiza Fraction Extracts (단삼 분획추출물의 암예방 효과)

  • Shon Yun-Hee;Cho Hyun-Jung;Chang Hyeun-Wook;Son Kun-Ho;Nam Kyung-Soo
    • Journal of Life Science
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    • v.16 no.3 s.76
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    • pp.369-374
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    • 2006
  • Six fractions of Salvia miltiorrhiza were tested for their chemopreventive potentials using biochemical markers of carcinogenesis such as quinone reductase (QR), glutathione S-transferase (GST) and glutathione (GSH). Seventy percentage of EtOH extract was potent inducer of QR activity in Hepa1c1c7 murine hepatoma cells. GST activity was increased about 1.4-fold with EtOAc extract at concentration of 50 ${\mu}g/ml$. GSH levels were significantly increased with $H_2O$ extract, 70% EtOH extract and water extract at concentration of 50 ${\mu}g/ml$ (p<0.005). From these results, 70% EtOH extract (250 mg/kg) was intragastrically administered to ICR mice for 14 days. QR, GST and GSH levels were significantly increased with the 70% EtOH treatment. These studies suggest that the 70% EtOH extract of S. miltiorrhiza could be considered as a potential agent for cancer chemoprevention.

The Effect of Fungicide Carbendazim on Hepatic detoxication systems of rat (살균제 carbendazim이 랫드 간 해독체계에 미치는 영향)

  • Lee, Je-Bong;Shin, Jin-Sup;Jeong, Mi-Hye;Park, Yeon-Ki;Kang, Kyu-Young
    • The Korean Journal of Pesticide Science
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    • v.9 no.4
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    • pp.338-346
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    • 2005
  • Serum alanine aminotransferase(ALT), aspartate aminotransferase (AST), hepatic glutathione, glutathione S-transferase(GST), cytochrome P450 and cytochrome P450 reductase activity were measured to investigate the effects of hepatic detoxication system and metabolic activities of carbendazim in Sprague Dawley(S.D.) male rat at dose levels of 375, 750 or 1,500 mg/kg body weight. Serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) activities were slightly increased in all test groups after 120 minutes of administration. Glutathione was increased about 20% at high and medium dose level within 120 minutes after administration, while activity of glutathione S-transferase was decreased $36{\sim}50%$. However, the enzyme activity was recovered from all test groups after 240 minutes of administration. Cytochrome P450 and activity of cytochrome P450 reductase were decreased $25{\sim}50%$ until 120 minutes after administration, but recovered after 240 minutes.

Gene Expression of Enzymes Related to Glutathione Metabolism in Anticancer Drug-resistant L1210 Sublines (항암제 내성 L1210세포의 Glutathione 대사 관련효소 유전자의 발현 양상)

  • Kim, Seong-Yong;Kim, Jae-Ryong;Kim, Jung-Hye
    • Journal of Yeungnam Medical Science
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    • v.12 no.1
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    • pp.32-47
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    • 1995
  • Glutathione(GSH) has a very important role in detoxification of cells and is closely related to antitumor drug-resistance of cancer cells. In order to evaluate the importance of glutathione metabolism in the drug-resistant cancer cells, the concentration of celluar GSH and activities of ${\gamma}$-glutamylcysteine synthetase(GCS), ${\gamma}$-glutamyl transpeptidase (GGT) and glutathione S-transferases(GST) in the adriamycin, vincristine, or cisplatin resistant L1210 (L1210AdR, L1210VcR, or L1210Cis) sublines were measured. Expression and amplification of GCS, GGT, and GST-${\pi}$ genes were also observed in the parent Ll210 and the drug-resistant Ll210 sublines. The concentration of GSH was increased 5.34 fold in L1210Cis, 2.83 fold in L1210VcR, and 1.78 fold in L1210AdR, compared to L1210. The activities of GCS and GGT were increased in drug-resistant L1210 sublines. The GST activity was increased in L1210VcR and L1210Cis but decreased in L1210AdR compared to Ll210. Expression of GCS, GGT, and GST-${\pi}$ genes were increased in the resistant L1210 sublines compare to the parent L1210 in northern blot analyses. Overexpression of GCS, GGT, and GST-${\pi}$ were observed in the resistant sublines, and the increases of the concentration of glutathione and the activities of GCS and GGT in the resistant sublines may be involved in a part of the drug-resistance in the resistant sublines.

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The Effect of Doenjang (Korean Soy Paste) on the Liver Enzyme Activities of the Sarcoma-180 Cell Transplanted Mice

  • Kim, Moon-Kyung;Moon, Suk-Hee;Park, Jong-Won;Park, Kun-Young
    • Preventive Nutrition and Food Science
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    • v.4 no.4
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    • pp.260-264
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    • 1999
  • Korean traditional fermented soy paste (doenjang) prolonged the life span of Balb/c mice injected with the sarcoma-180 cells. The activities of liver enzymes, such as xanthine oxidase, aminopyrine N-demethylase, aniline hydroxylase, ${\gamma}$-glutamylcysteine synthetase, glutathione reductase and glutathione S-transferase (GST), and the contents of lipid peroxide and glutathione were determined from the sarcoma-180 cell injected mice that were treated with methanol extracts from doenjang, miso and soybean. The content of lipid peroxide and the activity of xanthine oxidase in the liver of Balb/c mice which were increased by the transplantation of the sarcoma-180 cells were decreased by treatment with the methanol extract from doenjang. But the activities of aminopyrine N-dementhylase and aniline hydroxylase were not affected by the treatment of methanol extracts from doenjang to the mice injected with the sarcoma-180 cells. The content of glutathione, the activities of glutamylcysteine synthetase, glutathione reductase and glutathione S-transferase decreased by the injection of the sarcoma-180 were recovered considerably by the treatment of the methanol extract from doenjang.

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Modulation of Hepatic Lipid Peroxidation and Antioxidant Defenses by Wild Plants Extracts (야생초 추출물에 의한 간장내 활성산소 생성과 항산화 효소계 조절에 관한 연구)

  • Lee, Sang-Young;Kim, Sung-Wan;Kim, Jong-Dai
    • Korean Journal of Pharmacognosy
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    • v.28 no.1
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    • pp.48-53
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    • 1997
  • This study was performed to elucidate the possible antioxidative effects of several wild plant extracts. Wild plants were extracted with methanol or water using general method. In first experiments, antioxidative effects were measured by lipid peroxidation using rat brain homogenate. Coptis japonica extract showed the highest antioxidative activity among the 15 wild plant extracts. In second experiments, rats were fed on the semipurified diets with or without Coptis japonica extracts at the level of 0.5% for 4 weeks. MDA production of liver homogenate were significantly lower in the rats fed Coptis japonica extracts (P<0.05). Cytosolic catalase. GPX, and SOD activities were not changed, whereas the activities of GST and glutathione level were significantly higher in rats fed Coptis japonica extracts (P<0.05). These results suggest that Coptis japonica extract has an antioxidative effect through increasing GST activity and glutathione level and decreasing MDA production.

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Expression in Escherichia coli, Purification, and Characterization of the Tobacco Sulfonylurea Herbicide-Resistant Recombinant Acetolactate Synthase and Its Interaction with the Triazolopyrimidine Herbicides

  • Kil, Mee-Wha;Chang, Soo-Ik
    • BMB Reports
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    • v.31 no.3
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    • pp.287-295
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    • 1998
  • Acetolactate synthase (ALS) is the first common enzyme in the biosynthesis of L-Ieucine, L-isoleucine, and L-valine. The sulfonylurea-resistant ALS gene from Nicotiana tabacum was cloned into the bacterial expression vector pGEX-2T. The resulting recombinant plasmid pGEX-ALS3 was used to transform Escherichia coli strain XL1-Blue, and the mutant tobacco ALS (mALS) was expressed in the bacteria as a protein fused with glutathione S-transferase (GST). The fusion product GST-mALS was purified in a single step on a glutathione-Sepharose column. ALS activities of 0.9-2.5 ${\mu}mol/min/mg$ protein were observed in the GST-mALS, and the Km values for pyruvate, FAD, and TPP were 10.8-24.1, $(1.9-8.9){\times}10^{-3}$, and 0.14-0.38 mM, respectively. The purified GST-mALS was resistant to both the sulfonylurea and the triazolopyrimidine herbicides, and lost its sensitivity to end products, L-valine and L-leucine. For comparision, the tobacco wild-type recombinant ALS fused with GST, GST-wALS, was also characterized with respect to its pyruvate and cofactor bindings. These results suggest that the purified mutant recombinant tobacco ALS was functionally active, that the mutations resulting in herbicide resistance has affected pyruvate and cofactor bindings," and that the two classes of herbicides interact at a common site on the plant ALS.

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