• Title/Summary/Keyword: Glutathione S transferase

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Studies on Synthetic 1,2-Benzothiazine Anti-inflammatory Agents: Pharmacological Effect and the Expression of Xenobiotic-metabolizing Enzymes (1,2-Benzothiazine계열 새로운 항염진통제에 대한 약리작용 및 대사효소발현 유형의 연구)

  • 김상건;조주연;권순경;이은방
    • YAKHAK HOEJI
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    • v.44 no.4
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    • pp.300-307
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    • 2000
  • Expression of xenobiotic-metabolizing enzymes can be altered by xenobiotics, which represents changes in the production of reactive metabolic intermediates as well as toxicities in tissues. Metabolic intermediates derived from xenobiotics are considered to produce the reactive oxygen species including drug free radicals and hydroxyl free radicals, which would be ultimately responsible for drug-induced toxicities. The effects of 1,2-benzothiazine anti-inflammatory agents on the expression of xenobiotic-metabolizing enzymes including major cytochrome P450s, microsomal epoxide hydrolase (mEH) and glutathione S-transferase (GST) were studied in the liver with the aim of providing the part of information on potential production of reactive metabolites and hepatotoxicity by the agents. The synthetic compounds 24, 36 and 39 exhibited anti-inflammatory effects in rats as assessed by the Randall-Selitto method. The anti-inflammatory effect was detected as early as at 30 min after gavaging the agents with the ED5O being noted at 80 mg/kg, which was comparable to that of ibuprofen. Treatment of rats with each compound (100 mg/kg, 3d) resulted in no significant induction in the immunochemically-detectable cytochromes P45O 1A1/2, P450 2B1/2, P45O 2 Cl1 and P45O 2El. Changes in the mEN expression were also minimal, as evidenced by both Western blot and Northern blot analyses. Hepatic GST expression was slightly increased by the agents: GST Ya protein and mRNA expression was ~1.5-fold increased after treatment with compounds 24 and 39, whereas GST Yb1/2 and Yc1/2 mRNA levels were elevated 2- to 3-fold. In summary the effects of the synthetic 1,2-benzothiazines on the expression of major P45O, mEH and G57 were not significant, providing evidence that metabolic activation of the agents, potential drug interaction and hepatotoxicity would be minimal.

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SCG10, a Microtubule-Destabilizing Factor, Interacts Directly with Kinesin Superfamily KIF1A Protein in Brain (Kinesin superfamily KIF1A와 결합하는 미세소관 불안정화 단백질 SCG10의 규명)

  • Moon, Il-Soo;Seog, Dae-Hyun
    • Journal of Life Science
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    • v.19 no.7
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    • pp.859-865
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    • 2009
  • Microtubules, a major cytoskeleton, form parallel arrays in the axon and are oriented with their plus ends toward the cell periphery. Kinesin superfamily proteins (KIFs) are the molecular motors acting in the microtubule-based motilities of organelles in cells. Here, we used the yeast two-hybrid system to identify the protein that interacts with the coiled-coil domain of KIF1A and found a specific interaction with microtubule-destabilizing factor SCG10. SCG10 bound to the amino acid residues between 400 and 820 of KIF1A, but not to other KIFs in the yeast two-hybrid assay. The coiled-coil domain of SCG10 is essential for interaction with KIF1A. In addition, this specific interaction was also observed in the Glutathione S-transferase pull-down assay. An antibody to SCG10 specifically co-immunoprecipitated KIF1A associated with SCG10 from mouse brain extracts. These results suggest that KIF1A motor protein transports SCG10-containing vesicles along microtubules in neurons.

Isolation of Myrosinase and Glutathione S-transferase Genes and Transformation of These Genes to Develop Phenylethylisothiocyanate Enriching Chinese Cabbage (배추에서 항암물질 phenylethylisothiocyanate의 다량 합성을 위한 myrosinase와 glutathione S-transferase 유전자 분리 및 이를 이용한 형질전환체 육성)

  • Park, Ji-Hyun;Lee, Su-Jin;Kim, Bo-Ryung;Woo, Eun-Teak;Lee, Ji-Sun;Han, Eun-Hyang;Lee, Youn-Hyung;Park, Young-Doo
    • Horticultural Science & Technology
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    • v.29 no.6
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    • pp.623-632
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    • 2011
  • To increase the anti-carcinogens phenylethylisothiocyanate (PEITC), myrosinase (MYR), and glutathione S-transferase (GST), genes related to PEITC pathway were isolated and the gene expressions were regulated by Agrobacterium transformation. Isolated cDNAs, MYR, and GST genes were 1,647 bp and 624 bp, respectively, and the protein expression was confirmed through pET system. Thereafter, we constructed a sense-oriented over-expressing myrosinase (pBMY) and RNAi down-regulated GST (pJJGST) binary vectors for the Chinese cabbage transformation. After the transformation, thirteen over-expressing transgenic Chinese cabbage plants (IMS) with pBMY and five down-regulated ones (IGA) with pJJGST were selected by PCR analysis. Selected $T_0$ transgenic plants were generated to $T_1$ plants by self-pollination. Based on the Southern blot analysis on these $T_1$ transgenic plants, 1-4 copies of T-DNA were transferred to Chinese cabbage genome. Thereafter, RNA expression level of myrosinase gene or GST gene was analyzed through real-time RT PCR of IMS, IGA, and non-transgenic inbred lines. In case of IMS lines, myrosinase gene was increased 1.03-4.25 fold and, in IGA lines, GST gene was decreased by 26.42-42.22 fold compared to non-transgenic ones, respectively. Analysis of PEITC concentrations using GC-MS it showed that some IMS lines and some IGA lines increased concentrations of PEITC up to 4.86 fold and up to 3.89 fold respectively compared to wild type. Finally in this study IMS 1, 3, 5, 12, and 15 and IGA 1, 2, and 4 were selected as developed transgenic lines with increasing quantities of anti-carcinogen PEITC.

Chemopreventive Potential of Angelicae gigantis Radix Aqua-acupuncture Solution (당귀 약침액의 암예방 효과)

  • 김영기;조경희;손윤희;최혜경;김소연;임종국;남경수
    • YAKHAK HOEJI
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    • v.44 no.3
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    • pp.283-292
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    • 2000
  • Angelicae gigantis Radix aqua-acupuncture solution (AGRAS) and Angelicae gigantis Radix water-extracted solution (AGRWS) were prepared and tested for their organ toxicities and chemopreventive potentials. The organ-toxicity of AGRAS to male ICR mice was studied by the measurements of glutamic oxaloacetic transaminase (GOT), glutamic pyruvate transaminase (GPT), lactate dehydrogenase (LDH) and alkaline phosphatase (ALP-s) activities after injection of AGRAS for 7 days. The activities of GOT GPT and LDH were decreased, but the activity of ALP-s was not changed with AGRAS. When AGRAS was administered once daily for 10 days before the tumor implantation, AGRAS exerted antitumor activity by inhibiting the growth of Ehrich ascites tumor cells (EATC) in viva. The inductions of quinone reductase (QR), glutathione (GSH) and glutathione S-transferase (GST) and inhibition of polyamine metabolism were tested for the chemopreventive potentials of AGRAS and AGRWS. AGRAS was potent inducer of QR activity in murine hepatoma Hepalclc7 cells. In cultured rat Ac2F cells, AGRAS was also significantly induced QR activity GSH levels were increased about 1.3 fold with AGRAS. In addition the activity of GST was increased about 2.5 fold with AGRAS at the concentration of $0.1{\;}{\times}{\;}$. The effects of AGRAS and AGRWS were tested on the growth of Acanthamoeba castellanii. Proliferation of Acanthamoeba castellanii in a broth medium was inhibited by AGRAS and AGRWS at the concentration of $1{\;}{\times}{\;}and{\;}5{\;}{\times}{\;}$, respectively: These results suggest that AGRAS has chemopreventive potential by inducing QR activity increasing GSH and GST levels and inhibition of polyamine metabolism.

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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.

Hypoglycemic and Antioxidative Effects of Dietary Sea-Tangle Extracts Supplementation in Streptozotocin-Induced Diabetic Rats (Streptozotocin-유발 당뇨쥐에서 다시마 추출물 첨가식이의 항당뇨 및 항산화 효과)

  • 조영자;방미애
    • Journal of Nutrition and Health
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    • v.37 no.1
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    • pp.5-14
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    • 2004
  • The purpose of this study was to investigate the effect of dietary sea-tangle extracts on blood glucose levels, serum lipid levels, thiobarbituric acid reactive substance (TBARS) and glutathione enzymes in diabetic rats treated with streptozotocin (STZ) Four groups of rats (Sprague-Dawley male rats, 180 - 200g) were consisted of normal rats fed control diet (C), diabetic rats fed control diet (CD), normal rats fed sea-tangl extracts diet (E), and diabetic rats fed sea-tangle extracts diet (ED). Diabetes was induced by single injection of streptozotocin (60 mg/kg B.W.). After 7 weeks, rats were sacrificed, serum glucose, serum total cholesterol, triglyceride levels and glutathione enzymes were measured. Urine was significantly higher in CD and ED groups than those of others (p < 0.05). Levels of amylase, calcium, uric acid, hemoglobin, cholesterol and low density lipoprotein (LDL)-cholesterol were different among four groups. But high density cholesterol (HDL)-cholesterol of ED group was significantly higher (p < 0.05) than other groups (C and E group) And the weekly change of serum glucose was decreased in the 3th,4th and 5th weeks. But serum triglyceride (TG) of diabetic rats fed sea-tangle extracts diet (ED) was lower than diabetic rats fed control diet (CD). Activity of hepatic microsomal G6Pase was significantly increased CD and ED groups higher than C and E group, but kidney was decreased ED group. Hepateic glutathione S-transferase (GST) of CD and ED group were significantly lower than C and E group (p<0.05), glutathione peroxidase (GPX) of E and ED group were significantly higher than C and CD group (p<0.05), glutathione reductase (GR) activities of ED group was significantly lower than other groups, malondialdehyde (MDA) of ED was lower than E and CD group, but kidney was increased significant in ED group compared to liver. These results suggested that dietary sea-tangle extracts reduce .hepatic disorders such as oxidant than kidney. In conclusion, dietary sea-tangle extracts groups reduced blood TG and hepatic MDA levels in STZ-induced diabetic rats.

An Effect of Bromobenzene Treatment on the Liver Damage of Rats Previously Fed Low or High Protein Diet (단백식이 조건을 달리하여 성장시킨 흰쥐에 Bromobenzene 투여가 간손상에 미치는 영향)

  • 신중규;채순님;윤종국
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.23 no.6
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    • pp.894-898
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    • 1994
  • To evaluate an effect of dietary protein on the liver damage, the bromobenzene was intraperitoneally injected to the rats fed a low or high protein diet and then the liver weight per body weight and serum levels of alanine aminotransferase (ALT) activities were determined to demonstrate the differences in liver damage between the groups fed low or high protein diet. Hepatic aniline hydroxylase (AH), glutthione (GSH) content and glutathione s-transferase(GST) activity were also determined to clarify causes of liver damage between the two groups. Increases of liver weight per body weight and serum ALT activities were higher in brombenzene treated rats fed low protein diet than those fed high protein diet. The increasing rate of hepatic AH activity was higher in bromobenzne-treated rats fed low protein diet than that in those fed high protein diet. Furthermore , hepatic glutathione contents and GST activities in bromobenzene-treated rats were higher in rats fed high protein diet than those fed low protein diet. In case of control group, the heaptic glutathione content and GST activity were also higher in rats fed high protein diet than those fed low protein diet.

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Enhancement of Phase II and Antioxidant Enzymes in Mice by Soybeans Fermentation with Basidiomycetes

  • Shon, Yun-Hee;Kim, So-Yeun;Lee, Jae-Sung;Nam, Kyung-Soo
    • Journal of Microbiology and Biotechnology
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    • v.10 no.6
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    • pp.851-857
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    • 2000
  • The activities of phase II and antioxidant enzymes in the liver, lung, kidney, stomach, and colon of mice were examined following intragastric application of polysaccharides extracted from soybeans fermented with either Agrocybe Cylindracea (AC) or Phellinus ignarius (PI). The intragastric application of the extracts to mice for 14 days significantly increased the activities of quinone reductase (QP) and glutathione S-transferase (GST) in the liver and kidney, glutathione (GSH) and superoxide dismutase (SOD) in the liver, kidney, lung, and stomach, and glutathione peroxidase (GSH-Px) in the liver, lung, and kidney. In general, the elevation of the phase II and antioxidant enzymes activities was more pronounced in the liver and kidney as compared to the lung, stomach, and colon. Accordingly, these finding suggest that polysaccharides extracted from soybeans fermented with A. cylindracea or P. igniarius have a cancer chemopreventive potential in various target organs.

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Quantitative Assay for the Binding of Jun-Fos Dimer and Activator Protein-1 Site

  • Lee, Sang-Kyou;Park, Se-Yeon;Jun, Gyo;Hahm, Eun-Ryeong;Lee, Dug-Keun;Yang, Chul-Hak
    • BMB Reports
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    • v.32 no.6
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    • pp.594-598
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    • 1999
  • The Jun and Fos families of eukaryotic transcription factors form heterodimers capable of binding to their cognate DNA enhancer elements. We are interested in searching for inhibitors or antagonists of the binding of the Jun-Fos heterodimer to the activator protein-1 (AP-1) site. The basic-region leucine zipper (bZIP) domain of c-Fos was expressed as a fusion protein with glutathione S-transferase, and allowed to form a heterodimer with the bZIP domain of c-Jun. The heterodimer was bound to glutathione-agarose, to which were added radiolabeled AP-1 nucleotides. After thorough washing, the gel-bound radioactivity was counted. The assay is faster than the coventional electrophoretic mobility shift assay because the gel electrophoresis step and the autoradiography step are eliminated. Moreover, the assay is very sensitive, allowing the detection of picomolar quantities of nucleotides, and is not affected by up to 50% dimethylsulfoxide, a solvent for hydrophobic inhibitors. Curcumin and dihydroguaiaretic acid, recently known inhibitors of Jun-Fos-DNA complex formation, were applied to this Jun-GST-fused Fos system and revealed to decrease the dimer-DNA binding.

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Effects of Korean Green Tea, Oolong Tea and Black Tea Beverage on the Antioxidative Detoxification in Rat Poisoned with Cadmium (한국산 녹차, 우롱차 및 홍차가 카드뮴에 중독된 흰쥐 간조직의 항산화적 해독작용에 미치는 영향)

  • 윤연희
    • Journal of Nutrition and Health
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    • v.27 no.10
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    • pp.1007-1017
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    • 1994
  • In order to investigate the effect of Korean green tea, oolong tea and black tea beverage on the antioxidative detoxification in cadmium(Cd) poisoned rat liver, male Sprague-Dawley rat weighing 143$\pm$3.2g were divided into control and experimental groups. The experimental groups were fed standard diet containing 40ppm Cd and were given distilled water(CD), 5% black tea(BT), oolong tea(OT) and green tea(GT), respectively. Tea beverages were extracted from 5G dry leaves of teas in 100ml hot distilled water by the treatment at 85$^{\circ}C$ for 3 min. Liver xanthine oxidase(XOD) activity was increased by the administration of Cd except GT group. Liver superoxide dismutase(SOD), glutathione peroxidase(GSH-px), glutathione S-transferase(GST) activities were decreased by te administration of Cd but did not decreased by the administration of green tea(in GT group). Vitamin E and reduced glutathione contents were significantly decreased in Cd administered groups. Liver lipid peroxide value in Cd administered groups were increased compared to control group, but was not increased in GT group. Serum glutamic oxaloacetic transaminase(GOT) activities in CD, OT, BT groups were higher than control, but that in GT group was similar to control group. Serum glutamic pyruvic transaminase(GPT) activity was not significantly different among various groups. It was concluded that green tea might alleviate peroxidative damage in Cd-administered rat liver by reinforcing antioxidative detoxification system.

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