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

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PEP-1-GSTpi protein enhanced hippocampal neuronal cell survival after oxidative damage

  • Sohn, Eun Jeong;Shin, Min Jea;Kim, Dae Won;Son, Ora;Jo, Hyo Sang;Cho, Su Bin;Park, Jung Hwan;Lee, Chi Hern;Yeo, Eun Ji;Choi, Yeon Joo;Yu, Yeon Hee;Kim, Duk-Soo;Cho, Sung-Woo;Kwon, Oh Shin;Cho, Yong-Jun;Park, Jinseu;Eum, Won Sik;Choi, Soo Young
    • BMB Reports
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    • v.49 no.7
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    • pp.382-387
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    • 2016
  • Reactive oxygen species generated under oxidative stress are involved in neuronal diseases, including ischemia. Glutathione S-transferase pi (GSTpi) is a member of the GST family and is known to play important roles in cell survival. We investigated the effect of GSTpi against oxidative stress-induced hippocampal HT-22 cell death, and its effects in an animal model of ischemic injury, using a cell-permeable PEP-1-GSTpi protein. PEP-1-GSTpi was transduced into HT-22 cells and significantly protected against H2O2-treated cell death by reducing the intracellular toxicity and regulating the signal pathways, including MAPK, Akt, Bax, and Bcl-2. PEP-1-GSTpi transduced into the hippocampus in animal brains, and markedly protected against neuronal cell death in an ischemic injury animal model. These results indicate that PEP-1-GSTpi acts as a regulator or an antioxidant to protect against oxidative stress-induced cell death. Our study suggests that PEP-1-GSTpi may have potential as a therapeutic agent for the treatment of ischemia and a variety of oxidative stress-related neuronal diseases.

Systematic Identification of Hepatocellular Proteins Interacting with NS5A of the Hepatitis C Virus

  • Ahn, Ji-Won;Chung, Kyung-Sook;Kim, Dong-Uk;Won, Mi-Sun;Kim, Li-La;Kim, Kyung-Shin;Nam, Mi-Young;Choi, Shin-Jung;Kim, Hyoung-Chin;Yoon, Mi-Chung;Chae, Suhn-Kee;Hoe, Kwang-Lae
    • BMB Reports
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    • v.37 no.6
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    • pp.741-748
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    • 2004
  • The hepatitis C virus is associated with the development of liver cirrhosis and hepatocellular carcinomas. Among the 10 polyproteins produced by the virus, no function has been clearly assigned to the non-structural 5A (NS5A) protein. This study was designed to identify the hepatocellular proteins that interact with NS5A of the HCV. Yeast two-hybrid experiments were performed with a human liver cDNA prey-library, using five different NS5A derivatives as baits, the full-length NS5A (NS5A-F, amino acid (aa) 1~447) and its four different derivatives, denoted as NS5A-A (aa 1~150), -B (aa 1~300), -C (aa 300~447) and D (aa 150~447). NS5A-F, NS5A-B and NS5A-C gave two, two and 10 candidate clones, respectively, including an AHNAK-related protein, the secreted frizzled-related protein 4 (SFRP4), the N-myc downstream regulated gene 1 (NDRG1), the cellular retinoic acid binding protein 1 (CRABP-1), ferritin heavy chain (FTH1), translokin, tumor-associated calcium signal transducer 2 (TACSTD2), phosphatidylinositol 4-kinase (PI4K) and $centaurin{\delta}$ 2 ($CENT{\delta}2$). However, NS5A-A produced no candidates and NS5A-D was not suitable as bait due to transcriptional activity. Based on an in vitro binding assay, CRABP-1, PI4K, $CENT{\delta}2$ and two unknown fusion proteins with maltose binding protein (MBP), were confirmed to interact with the glutathione S-transferase (GST)/NS5A fusion protein. Furthermore, the interactions of CRABP-1, PI4K and $CENT{\delta}2$ were not related to the PXXP motif (class II), as judged by a domain analysis. While their biological relevance is under investigation, the results contribute to a better understanding of the possible role of NS5A in hepatocellular signaling pathways.

Biological Activities in roots of Glycyrrhiza uralensis Fisch (감초 세근의 생리활성 탐색)

  • Chung, Woo-Teak;Lee, Seo-Ho;Cha, Moon-Suk;Sung, Nak-Sul;Hwang, Baek;Lee, Hyeon-Yong
    • Korean Journal of Medicinal Crop Science
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    • v.9 no.1
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    • pp.45-54
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    • 2001
  • The biological activities of ethanol, ethanol: water(1 : 1v/v) and water extracts from Glycyrrhiza uralensis Fisch, glycyrrhizin and enzymatically hydrolyzed glycyrrhizin were compared. About 50% of the growth of MCF7, A549, Hep3B and AGS cells were inhibited in adding 1.0 g/L of the crude extracts, glycyrrhizin and enzymatically hydrolyzed glycyrrhizin. For example, the ethanol extract inhibited 76%, 66% in MCF7 and Hep3B cells by adding 1.0 g/L. For cytotoxicity on human normal liver cell(WRL-68), the crude extracts were scored as above 26%. For the result of antimutagenecity using CHO V79 cell, the crude extracts proved more effective than other samples. The growth of human immune B and T cells were enhanced up to $1.2{\sim}1.3$ times by adding the crude extracts. In inhibitory effect of ${\alpha}-glucosidase$ activity was showed that the ethanol extract, water extract and ethanol: water (1 : 1v/v) extract were appeared 65%, 68%, 62% in adding 1.0 g/L. The higher enhancement of glutathione -S-transferase activity was observed in the ethanol extract as 257% compared to the control in adding 1.0 g/L. From the results, the biological activities of the crude extracts were equivalent or higher than glycyrrhizin and enzymatically hydrolyzed glycyrrhizin.

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Anti-obesity Effects of Capsule-filled Cheonggukjang Added with Arrowroot (Pueraria thunbergiana) Extracts in ob/ob Mice (칡(Pueraria thunbergiana)추출물 청국장 캡슐의 ob/ob Mice에 대한 항비만 효과)

  • Kim, Kil-Soo;Hong, Joo-Heon;Kim, Dae-Ik
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.6
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    • pp.782-789
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    • 2012
  • This study was designed to evaluate the anti-metabolic syndrome effects of capsule-filled cheonggukjang (CGJ) added with arrowroot (Pueraria thunbergiana) extracts on body weight, adiposity and lipid metabolism in ob/ob mice. Experimental groups were normal control group (NC: basal diet), positive control group (PC: 2% CGJ), CGJ added with arrowroot extracts group (AR: 2% arrowroot in CGJ), and capsule-filled CGJ added with arrowroot extracts group (ARC: 2% arrowroot CGJ capsule). Each group was fed experimental diet for 10 weeks. Final body weight gain and atherogenic index were significantly lower in the ARC than NC group. Serum levels of total cholesterol, LDL-cholesterol, and triglycerides, blood glucose and atherogenic index were significantly lower in the ARC than NC group. Furthermore, fatty liver and regional lipid accumultion in ob/ob mice were inhibited in the ARC group. The hepatic activities of superoxide dismutase, catalase and glutathione S-transferase were significantly higher in the ARC than NC group. Therefore, the anti-matabolic syndrome effects of the ARC group were higher than the AR group. In conclusion, these results indicated that CGJ added with arrowroot mediates its anti-obesity effects in ob/ob mice by improving lipid metabolism and antioxidant enzyme.

The Relationship between the Polymorphism of CYP1A1, GSTM1, GSTT1, GSTP1 and p53 Overexpression in Head and Neck Squamous Cell Carcinoma (두경부 편평세포암종에서 CYP1A1, GSTM1, GSTT1, GSTP1 유전자 다형성 및 p53 과발현)

  • Tae Kyung;Park Hye-Kyung;Lee Seung-Hwan;Kim Kyung-Rae;Lee Hyung-Seok
    • Korean Journal of Head & Neck Oncology
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    • v.19 no.2
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    • pp.148-157
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    • 2003
  • Background and Objectives: Individual genetic susceptibilities to chemical carcinogens have been recognized as a major important host factors in human cancers. The cytochrome P450 family (CYPs) and glutathione S-transferase(GST) have been reported to be associated with risks to the smoking-related human cancers. Inactivation of tumor suppressor genes like p53 playa key role in tumor progression. The purpose of this study is to demonstrate an association between p53 overexpression and the prevalence of the genetic polymorphisms of CYP1A1 and GSTs in Korean head and neck squamous cell carcinoma (HNSCC). Materials and Methods: The polymorphisms of CYPIA1 and GSTs were analyzed by PCR and PCR-RFLP in 98 Korean head and neck squamous cell carcinoma patients. The expression of p53 was analyzed by immunohistochemistry with anti-p53 Ab (DO7). Results: Overexpression of p53 detected in 45.9% of HNSCC. The odds ratio for p53 overexpression in GSTM1(-), GSTT1(-), GSTP1(val/val) and CYP1A1(val/val) were 1.53, 1.83, 1.17 and 1.47, respectively. Among the combined genotypes, the odds ratio of the CYP1A1 val/val, GSTM1 (-), CYP1A1 val/val, GSTT1(-), and CYP1A1 val/val, GSTT1(-) were 2.0, 2.34 and 4.68, respectively. Conclusion: Based on our results, it might be suggested that p53 overexpression is slightly increased in GSTM1(-), GSTT1(-), GSTP1 val/val, CYP1A1 val/val genotypes. The further study is needed to evaluate the relationship and mechanism between the p53 overexpression and the specific CYP1A1 and GSTs genotypes.

Effect of Beni-Koji with Chitosan-Ascorbate on Serum Lipid Profile of Rats Fed a High Fat Diet (Chitosan-Ascorbate 함유 홍국이 고지방 식이 흰쥐의 혈청지질에 미치는 영향)

  • Shin Jin-Gi;Lee Sang-Il;Kwon Jung-Ho;Kim Soon-Dong
    • Journal of the East Asian Society of Dietary Life
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    • v.15 no.5
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    • pp.524-530
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    • 2005
  • Dietary effect of soyfiber beni-koji (SBK) with chitosan-ascorbate (CA) on the level of serum lipids in rats fed a high fat diet was investigated The experimental groups which were divided into high fat diet control group(HC-group), $2\%\;SBK+0.1\%$ CA mixture diet group(CA1-group), $2\%\;SBK+0.15\%$ CA mixture diet group(CA2-group), and $2\%\;SBK+0.2\%$ CA mixture diet group (CA2-group) were fed for 4 weeks. Weight gains in CA2- and CA3-group were $5.3\%\;and\;9.5\%$ lower than that of HC-group, respectively, while there was no significant difference in feed intakes, feed efficiency ratio and organs weight Level of serum triglyceride in $C_3-group\;was\;21\%$ lower than that of HC-group. Level of serum total cholesterol and LDL-cholesterol in CA2- and CA3-group were $22.1\~22.7\%\;and\;58.6\~64.3\%$ lower than those of HC-group, respectively. Atherogenic index decreased with the higher level of CA. Level of lipid peroxide in CA3-group was $24\%$ lower than that of HC-group, while there was no significant difference in GSH(Glutathione-S-transferase) content O type activities of XOD(xanthine oxidase) in the treated groups were lower, especially the activity in CA3-group was $51.6\%$ lower than that of HC-group. Also, O/T ratio of XOD was lower, showing $21.7\~23.5\%$ in treated groups and $34.0\%$ in HC-group(p<0.05). GST activities were 332.52 units in HC-group and $350.28\~355.63$ units in the treated groups, but there were no significant differences among them.

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Effect of Ramaria botrytis Methanol Extract on Hepatotoxicity in Benzo(α) Pyrene-treated Mice and Expression of Cytochrome P-450 1A1 Isozyme (벤조피렌 유발 마우스에서 싸리버섯 메탄올 추출물의 간 독성 억제효과 및 사이토크롬 P-450 1A1 Isozyme의 발현에 미치는 영향)

  • Kim, Hyun-Jeong;Lee, In-Seon;Bae, Jun-Tae;Kim, Ok-Mi;Park, Sun-Hee;Chang, Jong-Sun;Park, Jun-Hong;Lee, Kap-Rang
    • The Korean Journal of Mycology
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    • v.31 no.1
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    • pp.34-39
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    • 2003
  • This study was conducted to investigate effects of Ramaria botrytis methanol extract on liver damage in benzo$({\alpha})$pyrene(B$({\alpha})$P)-treated mice. The activities of serum amminotransferase, cytochrome P-450, aminopyrine N-demethylase, aniline hydroxylase and hepatic content of lipid peroxide after B$({\alpha})$P-treatment were increased than control, but those levels were significantly decreased by the treatment of Ramaria botrytis methanol extract. Whereas, the hepatic glutathione content and activities of glutathionie S-transferase and r-glutamylcysteine syntherase were increased by the treatment of Ramaria botrytis methanol extract. In addition, cytochrome P-450 1A1 izozyme protein level, remarkably increased by B$({\alpha})$P-treatment was decreased by the treatment with methanol extract of Ramaria botrytis. These results suggest that the protective effect of methanol extract of Ramaria botrytis on liver injury in B$({\alpha})$P-treated mice may be due to reduction of oxygen free radical.

Effect of Dietary Supplementation of Vitamin A or β-Carotene on Oxidative Damage Induced by Acute Ethanol Administration in Rats (비타민 A와 β-Carotene의 급여가 에탄올의 급성 투여에 의한 흰쥐의 산화적 손상에 미치는 영향)

  • 장정현;양경미;서정숙
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.31 no.1
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    • pp.81-86
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    • 2002
  • The present study was conducted to investigate the effect of dietary supplementation of vitamin A or $\beta$-carotene on oxidative damage induced by acute ethanol administration. Sprague-Dawley rats were fed on the experimental diets supplemented with retinyl acetate (2.86 mg/kg diet) or $\beta$-carotene (15.2 mg/kg diet) for 5 weeks. After fed the diet, rats were administered 20% ethanol solution (3g/kg B.W.) acutely. Lipid peroxide values in hepatic tissue, hepatic antioxidative enzyme activities and contents of antioxidative nutrient such as vitamins A and E in serum and hepatic tissue were measured. Hepatic level of malondialdehyde decreased in $\beta$-carotene group compared to the control group. However, there was no significant difference between retinal acetate and $\beta$-carotene groups. Superoxide dismutase activity was higher in retinal acetate group than in the control group. Hepatic glutathione-S-transferase activity of retinal acetate and $\beta$-carotene groups significantly decreased as compared with that of control group. The hepatic content of retinol increased in retinal acetate and $\beta$-carotene groups, especially, in retinyl acetate group. But there was no significant difference in serum content of retinol among the groups. Hepatic content of $\alpha$-tocopherol was significantly increased in retinyl acetate and $\beta$-carotene groups. In conclusion, acute ethanol administration might induce lipid peroxidation, and the dietary supplementation of retinyl acetate or $\beta$-carotene improve partly the antioxidative system through activation of superoxide dismutase and retention of hepatic $\alpha$-tocopherol in ethanol-treated rats.

Modulation of Cytochrome P-450 Induction by Long-Term Supplementation with Korean Red Ginseng to Rats (홍삼의 장기 투여가 흰쥐 간 대사효소 유도에 미치는 영향)

  • Lim, Heung-Bin
    • Korean Journal of Medicinal Crop Science
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    • v.15 no.6
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    • pp.437-443
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    • 2007
  • This study was carried out to investigate the effect of dietary supplementation with red ginseng water-extracts on the induction of microsomal cytochrome P-450 in rats. Phenobarbital (PB) and 3-methylcholanthrene (3-MC), P-450 inducers, were administered to 3- or 12-month old rats received red ginseng extracts (25 mg/kg) from 6 weeks to 12 months for 3 days. PB and 3-MC increased levels of P-450, P-450 reductase, ethoxycoumarin O-deethylase, benzphetamine N-demethylase and glutathione-S-transferase in the liver of rats. However, chronic administration of red ginseng significantly reduced these increase of enzyme levels induced by P-450 inducers. Chronic administration of red ginseng did not affect the induction of cytochrome $b_5$ and NADH cytochrome $b_5$ reductase by P-450 inducers. It is suggested that the induction of cytochrome P-450 system in the liver in relation to xenobiotics toxicity can be modulated by long-term supplementation with Korean red ginseng to rats.

Effects of Scutellaria baicalensis Water Extract on Lipid Metabolism and Antioxidant Defense System in Rats Fed High Fat Diet (황금추출물이 고지방 식이를 급여한 흰쥐의 지질대사 및 항산화방어계에 미치는 영향)

  • Yoon, Hye-Jin;Park, Young-Sook
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.2
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    • pp.219-226
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    • 2010
  • The objective of this study was to determine the effects of a Scutellaria baicalensis water extract (SDWE) on lipid levels, lipid peroxidation and antioxidant enzyme activities on rats fed a high fat diet for 6 weeks. Thirty-two male Sprague-Dawley rats (4-weeks-old) were randomly divided into four groups: normal diet and deionized water (ND), normal diet and Scutellaria baicalensis water extract (NDS), high fat diet and deionized water (HFD), high fat diet and Scutellaria baicalensis water extract (HFDS). The food intakes were significantly lower, but the food efficiency ratios were significantly higher in the high fat diet groups than those in other groups. The level of HDL-cholesterol and HDL-cholesterol/total cholesterol ratio in plasma were significantly higher and AI (atherogenic index) in HFDS group was significantly lower than that in HFD group. The level of triglyceride in plasma was significantly decreased in SDWE groups. The triglyceride of liver was significantly increased in the high fat diet groups and the total cholesterol of liver in the HFDS group was significantly lower than that in the HFD group. The plasma and liver concentrations of thiobarbituric acid reactive substances (TBARS) in the NDS group were significantly lower than those in the ND group. The total antioxidant status (TAS) in plasma was significantly increased in the HFDS group compared to the HFD group. The activities of SOD, catalase and GST were significantly increased in SDWE groups compared to ionized water groups. The activity of GSH-Px and the concentration of GSH in liver in the HFDS group were significantly higher than those in the HFD group. These results suggest that a supplement of SDWE on rats fed high fat diet reduce levels of lipid and lipid peroxidation in plasma and liver and improve the antioxidant defense systems.