• Title/Summary/Keyword: Glutathione S transferase

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Polymorphic Variation in Glutathione-S-transferase Genes and Risk of Chronic Myeloid Leukaemia in the Kashmiri Population

  • Bhat, Gulzar;Bhat, Ashaqullah;Wani, Aadil;Sadiq, Nida;Jeelani, Samoon;Kaur, Rajinder;Masood, Akbar;Ganai, Bashir
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.1
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    • pp.69-73
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    • 2012
  • Cancer is a complex disease and the genetic susceptibility to it could be an outcome of the inherited difference in the capacity of xenobiotic metabolizing enzymes. Glutathione-S-transferases (GSTs) are phase II metabolizing enzymes whose various genotypes have been associated with increased risk of different types of cancer. Null mutations caused by the deletion of the entire gene result in the absence of the enzymatic activity and increase in the risk of developing cancer including chronic myeloid leukaemia (CML). In the present case-control study we evaluated the effect of null mutations in GSTM1 and GSTT1 genes on the risk of developing CML. The study included 75 CML patients (43 males and 32 females; age (mean ${\pm}$ S.D) $42.3{\pm}13.4$ years) and unrelated non-malignant controls (76 male and 48 females; age (mean ${\pm}$ S.D) $41.5{\pm}12.9$). The distribution of GSTM1 and GSTT1 genotypes in CML patients and controls was assessed by multiplex-PCR method. Logistic regression was used to assess the relationship between GSTM1 and GSTT1 genotypes and risk of CML. Chi-square test was used to evaluate the trend in modulating the risk to CML by one or more potential high risk genotype. Although GSTM1 null genotype frequency was higher in CML patients (41%) than in the controls (35%), it did not reached a statistical significance (OD = 1.32, 95% CI: 0.73-2.40; P value = 0.4295). The frequency of GSTT1 null genotypes was higher in the CML patients (36%) than in the controls (21%) and the difference was found to be statistically significant (OD = 2.12, 95% CI: 1.12-4.02; P value = 0.0308). This suggests that the presence of GSTT1genotype may have protective role against the CML. We found a statistically significant (OD = 3.09, 95% CI: 1.122-8.528; P value = 0.0472) interaction between the GSTM1 and GSTT1 null genotypes and thus individuals carrying null genotypes of both GSTM1 and GSTT1 genes are at elevated risk of CML.

Increase in Hepatic DT-Diaphorase Activity by Chronic Administration of Panax ginseng Extract to Mice (생쥐에서의 인삼추출액의 장기간 투여에 의한 간장 DT-Diaphorase 활성의 증가)

  • Lee, Kang-Mee;Wie, Myung-Bok;Song, Dong-Keun;Kim, Yong-Sik;Kim, Yung-Hi
    • Journal of Ginseng Research
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    • v.17 no.2
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    • pp.123-126
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    • 1993
  • Effects of chronic administration of ginseng extracts (30 or 150 mg/kg/day for 52 days, p.o.) to mice on the activities of DT-diaphorase and glutathione S-transferase (GST) in the liver and the brain were studied. The DT-diaphorase activity in the liver was increased over 2-fold at the dose of both 30 and 150 mg/kg/day, while there was no change in the activity of the enzyme in the brain. The GST activity in the liver was increased in a dose-dependent fashion up to 142% of the control value at the dose of 150 mg/kg/day. while there was no change in the activity of the enzyme in the brain. The ginseng-induced increase in the activities of these hepatic phase II drug-metabolizing enzymes which are involved in the detoxification of carcinogens, is suggested to underlie, at least in part, the anticarcinogenic activity of Panax ginseng.

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The effect of caffeine on initiation step of diethylnitrosamine-initiated hepatic altered foci in a mid-term induction system (Caffeine이 diethylnitrosamine에 의해 유도되는 preneoplastic hepatic altered foci 형성의 initiation 단계에 미치는 효과)

  • Kim, Sung-ho;Lee, Cha-soo
    • Korean Journal of Veterinary Research
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    • v.31 no.3
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    • pp.337-342
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    • 1991
  • Caffeine이 랫트의 간조직에서 diethylnitrosamine(200mg/kg B.W., DEN)에 의해 유도되는 preneoplastic altered foci형성의 initiation단계에 미치는 효과를 관찰한 바 다음과 같은 결과를 얻었다. Altered foci의 지표로 사용되는 glutathione S-transferase(GST-P)-positive foci의 수는 caffeine 음수수 ml 당 2mg병행투여군 $(7.48{\pm}3.33)$ 및 1mg 병행 투여군 $(7.50{\pm}3.32)$ 모두에서 DEN 단독투여대조군$(14.08{\pm}5.16)$에 비하여 현저히 낮게 나타났으며, 면적 또한 caffeine 2mg병행투여군 $(0.29{\pm}0.17)$, 1mg병행투여군 $(0.30{\pm}0.13)$에서 DEN단독투여대조군 $(0.46{\pm}0.21)$에 비하여 유의성 있는 낮은 수치가 관찰되었다. 이러한 결과는 caffeine이 간암발생의 initiation 단계에 작용하여 억제효과를 나타냄을 암시하였다.

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Insecticide Resistance in Increasing Interest

  • Lee, Sung-Eun;Kim, Jang-Eok;Lee, Hoi-Seon
    • Journal of Applied Biological Chemistry
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    • v.44 no.3
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    • pp.105-112
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    • 2001
  • Insect pests can be controlled through direct application of insecticides. Insect control by residual protectants is relatively inexpensive and has an advantage of destroying all stages of infestations. The efficacy of control is largely determined by the concentration of insecticides to which the pest species is exposed. A reduction in the period of control in the field afforded by a specific level of a protectant indicates that resistance has developed. An increase in the level of protectant is required to maintain control, and the efficacy of currently used insecticides has been severely reduced by insecticide resistance in pest species. Development of resistance to particular insecticide varies with species because insecticide resistance is often correlated with increased levels of certain enzymes, which are cytochrome P450-dependent monooxygenases, glutathione S-transferases and esterases. Some sections of insecticide molecules can be modified by one or more of these primary enzymes. A reduction in the sensitivity of the action site of a xenobiotic also constitutes a mechanism of resistance. Acetylcholinesterase is a major target site for insecticide action, as are axonal sodium ion channels and ${\gamma}$-aminobutyric acid receptors. Development of reduced sensitivity of these target sites to insecticides usually occurs. This review not only may contribute to a better understanding of insecticide resistance, but also illustrates the gaps still present for a full biochemical understanding of the resistance.

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Effects of Betaine on the $CCI_4$-Induced Toxicity in Primary Cultured Rat Hepatocytes (일차 배양한 흰쥐의 간세포에서 사염화탄소로 인한 독성에 미치는 비테인의 효과)

  • Kim, Sun-Yeou;Kim, Hong-Pyo;Lee, Mi-Kyeong;Kim, Seung-Hee;Moon, Aree;Han, Hyung-Mi;Huh, Hoon;Kim, Young-Choong
    • YAKHAK HOEJI
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    • v.37 no.5
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    • pp.499-503
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    • 1993
  • Betaine, a major component of Lycii Fructus, was evaluated for its anti-hepatotoxic activity on carbon tetrachloride-induced hepatotoxicity in primary cultured rat hepatocytes. Betaine was found to attenuate carbon tetrachloride-induced hepatotoxicity both morphologically and biochemically. Typical hepatocyte necrosis due to carbon tetrachloride seemed to be reduced by 50 to 500 $\mu{M}$ of betaine under microscopical observation. The value of glutamic pyruvic transaminase released from the hepatocytes into the medium significantly decreased as betaine concentration increased. Betaine also significantly elevated the reduced activities of some enzymes, cytochrome P-450, 7-ethoxycoumarin-0-deethylase and glutathione-S-transferase, involved in xenobiotic metabolism due to carbon tetrachloride-induced hepatotoxicity. These results demonstrate a possible hepato-protective role of betaine against fatty liver that could be easily induced by carbon tetrachloride.

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Oxidative stress and non-specific immune responses in juvenile black sea bream, Acanthopagrus schlegelii, exposed to waterborne zinc

  • Kim, Jun-Hwan;Park, Hee-Ju;Kim, Kyeong-Wook;Kang, Ju-Chan
    • Fisheries and Aquatic Sciences
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    • v.20 no.6
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    • pp.11.1-11.8
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    • 2017
  • Juvenile black sea bream, Acanthopagrus schlegelii, were exposed to waterborne zinc (Zn) at concentrations of 0, 200, and $400{\mu}g/L$, at temperatures of 18 or $26^{\circ}C$ for 4 weeks. Superoxide dismutase (SOD) activities in the liver and gill of A. schlegelii significantly increased following exposure to waterborne Zn. Significant reduction in glutathione S-transferase (GST) activity in the liver and gill was observed following exposure to waterborne Zn. Glutathione (GSH) concentrations in the liver and gill also significantly decreased following exposure to waterborne Zn. Phagocytosis and lysozyme in the plasma and kidney were significantly increased following exposure to waterborne Zn. High water temperature increased alterations in the antioxidant and immune responses. The results of the present study suggest that waterborne Zn induced significant alterations in oxidative stress, increased immune responses and high temperature that trigger Zn toxicity.

Anti-Proliferative and Anti-Carcinogenic Enzyme-inducing Activities of Delphinidin in Hepatoma Cells

  • Jang, Chan-Ho;Lee, In-Ae;Lim, Hyun-Ae;Kim, Ju-Ryoung;Ha, Young-Ran;Yu, Hoon;Sung, Mi-Kyung;Kim, Jong-Sang
    • Food Science and Biotechnology
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    • v.16 no.4
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    • pp.641-645
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    • 2007
  • Delphinidin, an aglycone form of anthocyanins, was demonstrated to have anti-carcinogenic potential. The compound at $50\;{\mu}g/mL$ caused a significant increase of quinone reductase activity, an anti-carcinogenic marker enzyme, in mouse hepatoma cell lines (Hepa1c1c7 and BPRc1). Delphinidin enhanced the expression of other detoxifying or antioxidant enzymes including glutathione s-transferase, gamma-glutamylcysteine synthetase, heme oxygenase 1, and glutathione reductase. It suppressed the proliferation of murine hepatoma cells in a dose-dependent manner, with approximately $IC_{50}$ of $70\;{\mu}g/mL$. These results suggest that delphinidin might be useful for cancer prevention.

Effects of Adenophora triphylla Ethylacetate Extract on mRNA Levels of Antioxidant Enzymes in Human HepG2 Cells (인간 HepG2 Cell에서 항산화 효소의 mRNA 발현에 대한 잔대 에틸아세테이트 추출물 효과)

  • Choi, Hyun-Jin;Kim, Soo-Hyun;Oh, Hyun-Taek;Chung, Mi-Ja;Cui, Cheng-Bi;Ham, Seung-Shi
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.37 no.10
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    • pp.1238-1243
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    • 2008
  • The root of Adenophora triphylla is widely used as traditional herbal medicine in Korea. We studied its effects on sodium nitroprusside (SNP) cytotoxicity and antioxidant genes expression in HepG2 cells. To study whether Adenophora triphylla ethylacetate extract (ATea) inhibited NO-induced cell death, HepG2 cells were preincubated for 24 hr with 50 and 100 $\mu$g/mL ATea followed by 24-hr exposure to 0.5 mM SNP (exogenous NO donor). No-induced cytotoxicity was inhibited by pretreatment of ATea, as assessed by mitochondrial dehydrogenase activity (MTT assay). We further investigated the effects of ATea on mRNA levels of various enzymes of the antioxidant system such as Cu, Zn superoxide dismutase (SOD 1), Mn SOD (SOD 2), glutathione peroxidase (GPx), catalase and several enzymes of the glutathione metabolism [glutathione reductase (GR), $\gamma$-glutamyl-cystein synthetase (GCS), glutathione-S-transferase (GST), $\gamma$-glutamyltranspeptidase ($\gamma$-GT), glucose-6-phosphate dehydrogenase (G6PD)] by RT-PCR. CAT, GCS, GR and G6PD mRNA levels were increased after treatment with ATea. The SOD 1, SOD 2, GPx, GST and $\gamma$-GT mRNA levels were not affected in ATea-treated HepG2 cells. We concluded that ATea have an indirect antioxidant effects, perhaps via induction of CAT, GCS, GR and G6PD.

Association of GSTP1 and RRM1 Polymorphisms with the Response and Toxicity of Gemcitabine-cisplatin Combination Chemotherapy in Chinese Patients with Non-small Cell Lung Cancer

  • Yuan, Zhi-Jun;Zhou, Wen-Wu;Liu, Wei;Wu, Bai-Ping;Zhao, Jin;Wu, Wei;He, Yi;Yang, Shuo;Su, Jing;Luo, Yi
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.10
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    • pp.4347-4351
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    • 2015
  • Background: Previous studies showed that genetic polymorphisms of glutathione S-transferase P1 (GSTP1) were involved in glutathione metabolism and genetic polymorphisms of ribonucleotide reductase (RRM1) were correlated with DNA synthesis. Here we explored the effects of these polymorphisms on the chemosensitivity and clinical outcome in Chinese non-small cell lung cancer (NSCLC) patients treated with gemcitabine-cisplatin regimens. Materials and Methods: DNA sequencing was used to evaluate genetic polymorphisms of GSTP1 Ile105Val and RRM1 C37A-T524C in 47 NSCLC patients treated with gemcitabine-cisplatin regimens. Clinical response was evaluated according to RECIST criteria after 2 cycles of chemotherapy and toxicity was assessed by 1979 WHO criteria (acute and subacute toxicity graduation criteria in chemotherapeutic agents). Results: There was no statistical significance between sensitive and non-sensitive groups regarding the genotype frequency distribution of GSTP1 Ile105Val polymorphism (p>0.05). But for RRM1 C37A-T524C genotype, sensitive group had higher proportion of high effective genotype than non-sensitive group (p=0.009). And according to the joint detection of GSTP1 Ile105Val and RRM1 C37A-T524C polymorphisms, the proportion of type A (A/A + high effective genotype) was significantly higher in sensitive group than in non-sensitive group (p=0.009). Toxicity showed no correlation with the genotypes between two groups (p>0.05). Conclusions: Compared with single detection of genetic polymorphisms of GSTP1 Ile105Val or RRM1 C37A-T524C, joint detection of both may be more helpful for patients with NSCLC to receive gemcitabine-cisplatin regimens as the first-line chemotherapy. Especially, genetic polymorphism of RRM1 is more likely to be used as an important biomarker to predict the response and toxicity of gemcitabine-cisplatin combination chemotherapy in NSCLC.

Production of the recombinant fibronectin-binding protein of Staphylococcus aureus (Staphylococcus aureus의 재조합 fibronectin-binding protein의 생산)

  • kim, Doo;Cheong, Cha-ryong;Park, Hee-myong;Han, Hong-ryul
    • Korean Journal of Veterinary Research
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    • v.37 no.4
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    • pp.875-882
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    • 1997
  • To produce the recombinant fibronectin-binding protein(FnBP) for development of subunit vaccine against Staphylococcus aureus. The fnbp gene was amplified from the chromosomal DNA of S aureus KNU 196 strain using the polymerase chain reaction, and cloned into pGEX-4T-2. Then, the recombinant FnBP fused with glutathione-S-transferase was produced in E coli, purified by affinity chromatography, and identified its antigenicity and immunogenicity by Western blot. The recombinant FnBP produced in this study is considered to have the same property of native FnBP purified from S aureus, and is expected to be useful as a candidate for S aureus subunit vaccine.

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