• Title/Summary/Keyword: Methyl transferase

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Effects of Methly Group Deficiency on Hepatic Lipid Peroxidation in Diethylnitrosamine and 2-Acetylaminofluorene Treated Rats (메틸기 결핍이 Diethylnitrosamine과 2-Acetylaminofluorene을 투여한 쥐 간의 지질과산화도에 미치는 영향)

  • 김현아
    • Journal of Nutrition and Health
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    • v.25 no.2
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    • pp.116-122
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    • 1992
  • This study determined hepatic microsomal lipid peroxide values glucose 6-phosphatase NA-DPH-cytochrome P450 reductase and cytosolic glutathione S-transferase activites to examine the effects of methyl group deficiency on hepatic lipid peroxidation in rats treated with diethylni-trosamine(DEN) and 2-acetylamionfluorene(AAF) Weanling sprague Dawley male rats were fed the diet with methyl group supplemented or deficient. Two weeks after feeding rate were injected with a single of 200mg/kg body weight DEN intraperitoneally and after four weeks 0.02% AAF containing diets were fed for two weeks. Animals were sacrificed at 6th week. Microsomal lipid peroxide values were tended to increase in methyl group deficiency(MD). Especially in case of carcinogen tratments lipid peroxide values were increased significantly in MD. Microsomal glucose 6-phophatase activities were decreased by MD and carcinogens and in MD with carcinogen group (MD+C) the enzyme activites were the lowest Glucose 6-phosphatase activities were negatively correlated with lipid peroxidation. Microsomal NADPH-cytochrome P450 reductase activities were the highest in MD+C and correlated positively with lipid peroxidation. Cytosolic glutathione S-transferase activities were the highest in MD+C Methyl group deficiency induces lipid peroxidation especially in case of being exposed to carcinogens. Therefore the results suggest that lipid peroxidation may be one of the meachanisms of carcinogensis by methyl group deficiency.

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Cloning of the Setd1b gene of Mus musculus, a novel histone methyl transferase target in the epigenetic therapy of cancers

  • Morishita, Masayo;Cho, Minju;Ryu, Juhee;Mevius, Damiaan E.H.F.;Di Luccio, Eric
    • 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.

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Effect of Garlic (allium sativum) on Glutathione S-Transfer Activity and the Level of Glutathione in the Mouse Liver (마늘이 생쥐간에서 Glutathione S-transferase 활성과 Glutathione 생성에 미치는 영향)

  • Kim, So-Hee;Park, Kun-Young;Suh, Meong-Ja;Chung, Hae-Young
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.23 no.3
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    • pp.436-442
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    • 1994
  • The effect of garlic on glutathione S-transferase activity and the level of glutathione in the mouse liver was studied. the intraperitoneal injection of the methanol extract of garlic and ally sulfide which is one of possible active compounds in garlic to ICR mouse before the injection of aflatoxin B1 (AFB1) increased the levels of glutathione and nonprotein-SH in microsomal fraction of the livers. The injection of the chloroform fraction 2 which revealed the highest antimutgenic activity in our previous research in the increase of the activity of glutathione S-transferase and the levels of glutathione and nonprotein -SH. The glutathione itself also had the antimutagenic effect on AFB1 and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Salmonella typhimurium TA98 and TA100 in vitro.

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Site-directed Mutagenesis of Arginine 13 Residue in Human Glutathione S-Transferase P1-1

  • Koh, Jong-Uk;Cho, Hyun-Young;Kong, Kwang-Hoon
    • Bulletin of the Korean Chemical Society
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    • v.28 no.5
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    • pp.772-776
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    • 2007
  • In order to study the role of residue in the active site of glutathione S-transferase (GST), Arg13 residue in human GST P1-1 was replaced with alanine, lysine and leucine by site-directed mutagenesis to obtain mutants R13A, R13K and R13L. These three mutant enzymes were expressed in Escherichia coli and purified to electrophoretic homogeneity by affinity chromatography on immobilized GSH. Mutation of Arg13 into Ala caused a substantial reduction of the specific activity by 10-fold. Km GSH, Km DCNB and Km EPNP values of R13A were approximately 2-3 fold larger than those of the wild type. Mutation of Arg13 into Ala also significantly affected I50 values of S-methyl-GSH that compete with GSH and ethacrynic acid, an electrophilic substrate-like compound. These results appeared that the substitution of Arg13 with Ala resulted in significant structural change of the active site. Mutation of Arg13 into Leu reduced the catalytic activity by approximately 2-fold, whereas substitution by Lys scarcely affected the activity, indicating the significance of a positively charged residue at position 13. Therefore, arginine 13 participates in catalytic activity as mainly involved in the construction of the proper electrostatic field and conformation of the active site in human GST P1-1.

Inhibitory activity of diarylheptanoids on farnesyl protein transferase

  • Kang, Hyun-Mi;Jeon, Sun-Bok;Son, Kwang-Hee;Yang, Deok-Cho;Han, Dong-Cho;Kwon, Byoung-Mog
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.265.2-265.2
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    • 2003
  • Diarylheptanoids [curcumin (1), demethoxycurcumin (2), bisdemethoxycurcumin (3), bisdimethoxymethylcurcumin (4), and 1,2-dihydrobis(de-O-methyl)curcumin (5)] were isolated from the methanolic extract of Curcuma longa L. and A new cyclic diarylheptanoiid (6) and a known compound 7 were isolated from fruits of Alnus japonica S. Diarylheptanoids (1-3) inhibited farnesyl protein transferase (FTPase) with an IC50 of 29-50 $\mu\textrm{m}$. (omitted)

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No Association between Val108/158Met Polymorphism on Catechol-O-Methyl Transferase(COMT) Gene and Smooth Pursuit Eye Movement(SPEM) Abnormality in Korean Schizophrenia Patients (한국인 정신분열병 환자의 안구추적운동 이상과 COMT 유전자의 Val108/158Met 다형성의 연합 연구)

  • Jang, Ho Joon;Moon, Hyun-Il;Lee, Yeon Jung;Kim, Im-Yel;Lee, In-Sang;Seo, Han-Gil;Kim, Ki-Hoon;Shin, Tae-Min;Park, Byung-Lae;Shin, Hyung Doo;Han, Sun Ho;Han, Sang-Woo;Woo, Sung-Il
    • Korean Journal of Biological Psychiatry
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    • v.15 no.4
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    • pp.288-296
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    • 2008
  • Objectives : We investigated the association of Val108/158Met polymorphism on catechol-O-methyl transferase(COMT) gene with smooth pursuit eye movement(SPEM) abnormality in Korean schizophrenia patients. Methods : We measured SPEM in 217 Korean schizophrenia patients(male 116, female 101) and divided them into two groups, one was a good SPEM function group and the other was a poor SPEM function group. Then we analyzed Val108/158Met polymorphism on COMT gene. We compared the differences of genotype and allele distributions of the polymorphism on COMT gene between the two groups. Results : The natural logarithm value of signal/noise ratio(Ln S/N ratio) of the good SPEM function group was $4.39{\pm}0.33$(mean${\pm}$s.d.) and that of poor SPEM function group was $3.17{\pm}0.71$. There were no statistically significant differences of age and male/female ratio between the two groups. There were no significant differences of genotype or allele distributions of the Val108/158Met polymorphism on COMT gene between the two schizophrenic groups. Conclusions : The results suggest that Val108/158Met polymorphism on COMT gene is not related to SPEM function abnormality in schizophrenia.

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