• Title/Summary/Keyword: glutathione transferase

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Human Glutathione S-Transferase P1 Suppresses MEKK1-mediated Apoptosis by Regulating MEKK1 Kinase Activity in HEK293 Cells

  • Zhao, Xin;Fan, Yumei;Shen, Jiayin;Wu, Yifan;Yin, Zhimin
    • Molecules and Cells
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    • v.21 no.3
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    • pp.395-400
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    • 2006
  • Glutathione S-transferase P1 (GSTP1) plays an important role in detoxification and the metabolism of xenobiotics. Here we show that GSTP1 also regulates the MEKK1-MKK7 signaling pathway. Over-expression of GSTP1 in HEK293 cells inhibited both ${\Delta}MEKK1$- and etoposide-induced apoptosis, and inhibited procaspase-3 activation and PARP cleavage. MEKK1- induced apoptosis requires both its kinase activity and proteolytic cleavage. ${\Delta}MEKK1$ activity was inhibited by over-expression of GSTP1 in vivo and MEKK1 kinase activity was also inhibited by GSTP1 in vitro when assayed with bacterially-expressed MKK7(KM) protein as substrate. GSTP1 inhibition of etoposide-induced cell apoptosis was mainly due to its ability to suppress MEKK1 kinase activity. The glutathione-conjugating activity of GSTP1 was essential for the above effects. These findings provide insight into the mechanism by which GSTP1 protects cells from genotoxin-induced apoptosis.

Effects of Acori Graminei Rhizoma Aqua-acupunture Solution(AGRAS) on Induction of Cancer Chemopreventive Enzymes (석창포(石菖蒲) 약침액(藥鍼液)의 암(癌) 예방(豫防) 관련 효소 유도 효과)

  • Roh Dong-Il;Lim Jong-Kook
    • Korean Journal of Acupuncture
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    • v.19 no.2
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    • pp.51-56
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    • 2002
  • Induction of phase II enzymes such as quinone reductase (QR) and glutathione S-transferase (GST) is considered a major mechanism of protection against initiation of carcinogenesis. The present study was performed to evaluate the chemopreventive activity of Acori Graminei Rhizoma aqua-acupuncture solution (AGRAS) and Acori Graminei Rhizoma water-extracted solution (AGRWS) by measuring the induction of phase II enzymes. AGRAS and AGRWS are potent inducers of quinone reductase activity in murine hepatoma Hepa1c1c7 cells. The levels of GSH and GST was increased sightly with AGRAS and AGRWS. These results suggest that AGRAS and AGRWS may act as blocking agents against carcinogenesis by induction of phase II enzymes.

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Site-directed Mutagenesis of Cysteine Residues in Phi-class Glutathione S-transferase F3 from Oryza sativa

  • Jo, Hyun-Joo;Lee, Ju-Won;Noh, Jin-Seok;Kong, Kwang-Hoon
    • Bulletin of the Korean Chemical Society
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    • v.33 no.12
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    • pp.4169-4172
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    • 2012
  • To elucidate the roles of cysteine residues in rice Phi-class GST F3, in this study, all three cysteine residues were replaced with alanine by site-directed mutagenesis in order to obtain mutants C22A, C73A and C77A. Three mutant enzymes were expressed in Escherichia coli and purified to electrophoretic homogeneity by affinity chromatography on immobilized GSH. The substitutions of Cys73 and Cys77 residues in OsGSTF3 with alanine did not affect the glutathione conjugation activities, showing non-essentiality of these residues. On the other hand, the substitution of Cys22 residue with alanine resulted in approximately a 60% loss of specific activity toward ethacrynic acid. Moreover, the ${K_m}^{CDNB}$ value of the mutant C22A was approximately 2.2 fold larger than that of the wild type. From these results, the evolutionally conserved cysteine 22 residue seems to participate rather in the structural stability of the active site in OsGSTF3 by stabilizing the electrophilic substrates-binding site's conformation than in the substrate binding directly.

The Effect of Lycii fructus beer intake on serum lipid profiles and antioxidant activity in rats (구기자 맥주의 섭취가 흰쥐의 혈청 지질패턴 및 항산화효소 활성에 미치는 영향)

  • Chung, Hae-Kyung;Choi, Chang-Suk;Yang, Eun-Ju;Kang, Myung-Hwa
    • Journal of the Korean Society of Food Culture
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    • v.19 no.1
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    • pp.52-60
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    • 2004
  • This study was performed to investigate the effect of Lycii fructus beer on serum lipid profiles and antioxidant activity in rat Sprague-Dawley (SD) rats weighting about 190g were divided into the following 5 groups ; distillate water (Control), 5% ethanol in distillate water (Ethanol), commercial beer (CB), Lycii fructus beer (LFB) and 5% alcohol red wine diluted with distillate water (RW). Body weight, total food intake, FER and percent organ (liver, kidney) weight per body weight were not significantly changed by Lycii fructus beer drinking. After 6 weeks, serum total cholesterol, triglyceride and HDL cholesterol level were not significantly different. But, Lycii fructus beer intake tended to decrease serum triglyceride level and atherogenic index. Also, GOT and GPT levels were expressed lower than Ethanol group. There was not significantly different in hepatic glutatiione (GSH) content and glutathione-S-transferase (GST) activities among 5 groups. Lipid peroxidation in the hepatic was decreased by Lycii fructus beer intake. The results demonstrated that Lycii fructus beer was potential and effective antioxidant that can protect the decrease associated with alcohol.

Effect of Cnidii Rhizoma on Phase II Enzyme and Ornithine Decarboxylase Activities (천궁이 Phase II 효소 유도와 Ornithine Decarboxylase 활성에 미치는 영향)

  • Shon, Yun-Hee;Kim, Mee-Kyung;Cho, Hyun-Jung;Nam, Kyung-Soo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.6
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    • pp.1572-1575
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    • 2006
  • Water extract from Cnidii Rhizoma (CRW) was tested for colon cancer chemopreventive activity by measuring the induction of phase II detoxification enzyme activity [quinone reductase (QR) and glutathione S-transferase (GST)] and glutathion (GSH) levels and ornithine decarboxylase (ODC) activity in cultured human colorectal adenocarcinoma HT-29 cells. CRW inhibited cell proliferation in cultured HT-29 cells. CRW induced QR activity in a dose-dependent manner in a concentration range of 0.1${\sim}$5.0 $mg/m{\ell}$. GST activity was also induced with the treatment of CRW in HT-29 cells. In addition GSH levels was increased with CRW. CRW inhibited ODC activity, a key enzyme of polyamine biosynthesis, which is enhanced in tumor promotion. These results suggest that CRW has colon cancer chemopreventive activity by increasing phase II enzyme activity and GSH levels and inhibiting ODC activity in vitro.

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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Induction of Hepatic Glutathione S-transferase Activity in Mice Administered with Various Vegetable Extracts

  • Kim, Mee-Ree;Lee, Kun-Jong;Kim, Yun-Bae;Sok, Dai-Eun
    • Preventive Nutrition and Food Science
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    • v.2 no.3
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    • pp.207-213
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    • 1997
  • The effect of various vegetables commonly consumed by Koreans on the induction of glutathione S-trasferase(GST) activity in mice was assessd. The extract of vegetable dissolved in propylene glycol (5ml/kg body wt.) was administered to ICR female mice 6 to 8 weeks old via gavage during 5 days. The changes of body weight and liver weight of all treated groups were not significantly different compared with control group. Hepatic protein contents of trated groups compared with control group were not significantly different except BHT treated group. The induction of GST activity in liver cytosol of mice was the greatest with broccoli, followed by radish, wild green onion, turnip, and green onion. The induction of GST activity in liver cytosol increased up to 1.5 to 1.8-folds at a dose of 24 g fresh vegetable/mouse. The induction of combination between vegetables was the highest with the combination of broccoli and radish (1.83-fold), followed by that of broccoli and green onion (1.72-fold), and that of broccoli and turnip (1.50-fold).

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