• Title/Summary/Keyword: glutathione- S-transferase

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Toluene Tolerance in Solvent Tolerant Pseudomonas sp. Strains By Antioxidant Defense Systems (항산화 방어 시스템에 의한 유기용매 내성세균 Pseudomonas sp. 균주에서의 톨루엔 내성)

  • Joo, Woo Hong;Choi, Hye Jung;Kim, Da Som;Cho, Yong-Kweon;Kim, Dong Wan
    • Journal of Life Science
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    • v.29 no.12
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    • pp.1401-1407
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    • 2019
  • To elucidate whether or not solvent-tolerant bacteria use anti-oxidative defense systems to defend themselves against toxic solvents, oxidative enzyme activity and total anti-oxidative capacity (T-AOC) were investigated in two tolerant strains of Pseudomonas sp. under toluene stress. The superoxide dismutase (SOD) activities of solvent tolerant BCNU 106 exhibited relatively increased levels at a toluene concentration of 100 mg/l, where those of solvent tolerant BCNU 171 increased at 200 mg/l. A greater than three-fold increase in catalase (CAT) levels was observed at concentrations of 200 and 300 mg/l in BCNU 106, and a two-fold increase was monitored at the same concentrations in BCNU 171. High glutathione S-transferase (GST) levels were also observed in the solvent tolerant bacteria. Higher levels of T-AOC was expressed in the solvent tolerant strains than in the ordinary non-tolerant KACC 10266. The highest plateau of SOD in BCNU 171 was observed at 1 hr of toluene exposure. CAT levels plateaued at 1 hr and 14 hr in BCNU 106 and reached the highest plateau at 3 hr in BCNU 171. The highest peak of T-AOC occurred at 9 hr in BCNU 106, and two high peaks occurred in BCNU 171, at 1 hr and at 9 hr of toluene exposure. The solvent-tolerant bacteria showed active antioxidant responses and could survive under harsh environments, including the presence of solvents, through means of antioxidant defense systems.

Interaction of GAT1 with Ubiquitin-Specific Protease Usp14 in Synaptic Terminal (GAT1과 ubiquitin-specific protease Usp14의 결합)

  • Seog, Dae-Hyun;Kim, Sang-Jin;Joung, Young-Ju;Yea, Sung-Su;Park, Yeong-Hong;Kim, Moo-Seong;Moon, Il-Soo;Jang, Won-Hee
    • Journal of Life Science
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    • v.20 no.7
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    • pp.1005-1011
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    • 2010
  • $\gamma$-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system. GABA transporters (GATs) control extracellular GABA levels by reuptake of released GABA from the synaptic cleft. However, how GATs are regulated has not yet been elucidated. Here, we used the yeast two-hybrid system to identify the specific binding protein(s) that interacts with the carboxyl (C)-terminal region of GAT1, the major isoform in the brain and find a specific interaction with the ubiquitin-specific protease 14 (Usp14), a deubiquitinating enzyme. Usp14 protein bound to the tail region of GAT1 and GAT2 but not to other GAT members in the yeast two-hybrid assay. The C-terminal region of Usp14 is essential for interaction with GAT1. In addition, these proteins showed specific interactions in the glutathione S-transferase (GST) pull-down assay. An antibody to GAT1 specifically co-immunoprecipitated Usp14 from mouse brain extracts. These results suggest that Usp14 may regulate the number of GAT1 at the cell surface.

A Case-Control Study on Effects of Genetic Polymorphisms of GSTM1, GSTT1, CYP1A1 and CYP2E1 on Risk of Lung Cancer (GSTM1과 GSTT1, 그리고 CYP1A1, CYP2E1 다형성이 폐암발생에 미치는 영향에 대한 환자-대조군연구)

  • Nan, Hong-Mei;Kang, Jong-Won;Bae, Jang-Whan;Choe, Kang-Hyeon;Lee, Ki-Hyeong;Kim, Seung-Taik;Won, Choong-Hee;Kim, Yong-Min;Kim, Heon
    • Journal of Preventive Medicine and Public Health
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    • v.32 no.2
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    • pp.123-129
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    • 1999
  • Objectives: This study was performed to investigate sweets of genetic polymorphisms of glutathione S-transferase M1 (GSTM1), glutathione S-transferase M1 (GSTT1), cytochrome P450 1A1 (CYP1A1) and cytoehrome P450 2E1 (CYP2E1) on lung cancer development. Methods: Ninety-eight lung cancer patients and 98 age-sex matched non-cancer patients hospitalized in Chungbuk National University Hospital form March 1997 to August 1998, were the subjects of this case-control study. Direct interview was done and genotypes of GSTM1, GSTT1, CYP1A1 and CYP2E1 were investigated using multiplex PCR or PCR-RFLP methods with DNA extracted from venous blood. Effects of the polymorphisms of GSTM1, GSTT1, CYP1A1 and CYP2E1, lifestyle factors including smoking, and their interactions on lung rancor were statistically analyzed. Results: GSTM1 was deleted in 67.01% of the cases and 58.16% of the controls, and the odds ratio(95% CI) was 1.46(0.82-2.62). GSTT1 deletion was 58.76% for the lung cancer patients and 50.00% for the controls[OR:1.43(0.81-2.51)]. The frequencies of lle/lle, lle/Val and Val/Val of the CYP1A1 polymorphisms were 59.18-18%, 35.71%, and 5.10% for the cases, and 52.04%, 45.92%, 2.04% for the controls, respectively. Risk of lung cancer was not associated with polymorphism of CYP1A1 ($x^2trend=0.253$, p-value>0.05). The respective frequency of c1/c1 c1/c2, c2/c2 genotypes for CYP2E1 were 50.00%, 42.86%, 7.14% for the lung cancer patients, and 66.33%, 30.61%, 3.06% for the controls $(x^2trend=5.783,\;p<0.05)$. c2 allele was a significant risk factor for lung cancer. We also observed a significant association of cigarette smoking history with lung cancer risk. The odds ratio(95% Cl) of cigarette smoking was 3.03(1.58-5.81). In multiple logistic analysis including genotypes of GSTM1, GSTT1, CYP1A1 and CYP2E1, and smoking habit, only snaking habit came out to be a significant risk factor for lung cancer. Conclusion: Genetic polymorphisms of GSTM1, GSTT1, CYP1A1 and CYP2E1 are not so strongly associated with lung cancer as lifestyle factors including cigarette smoking.

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CYP1A1 (Ile462Val), CYP1B1 (Ala119Ser and Val432Leu), GSTM1 (null), and GSTT1 (null) Polymorphisms and Bladder Cancer Risk in a Turkish Population

  • Berber, Ufuk;Yilmaz, Ismail;Yilmaz, Omer;Haholu, Aptullah;Kucukodaci, Zafer;Ates, Ferhat;Demirel, Dilaver
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.6
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    • pp.3925-3929
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    • 2013
  • We aimed to investigate bladder cancer risk with reference to polymorphic variants of cytochrome p450 (CYP) 1A1, CYP1B1, glutathione S-transferase (GST) M1, and GSTT1 genes in a case control study. Polymorphisms were examined in 114 bladder cancer patients and 114 age and sex-matched cancer-free subjects. Genotypes were determined using allele specific PCR for CYP1A1 and CYP1B1 genes, and by multiplex PCR and melting curve analysis for GSTM1 and GSTT1 genes. Our results revealed a statistically significant increased bladder cancer risk for GSTT1 null genotype carriers with an odds ratio of 3.06 (95% confidence interval=1.39-6.74, p=0.006). Differences of CYP1A1, CYP1B1 and GSTM1 genotype frequencies were not statistically significant between patients and controls. However, the specific combination of GSTM1 null, GSTT1 null, and CYP1B1 codon 119 risk allele carriers and specific combination of GSTM1 present, GSTT1 null, and CYP1B1 432 risk allele carriers exhibited increased cancer risk in the combined analysis. We did not observe any association between different genotype groups and prognostic tumor characteristics of bladder cancer. Our results indicate that inherited absence of GSTT1 gene may be associated with bladder cancer susceptibility, and specific combinations of GSTM1, GSTT1 and CYP1B1 gene polymorphisms may modify bladder cancer risk in the Turkish population, without any association being observed for CYP1A1 gene polymorphism and bladder cancer risk.

Inhibition of Vinyl Carbamate Epoxide- and 2`-(4-Nitrophenoxy)oxirane-induced Mutagenicity by Various Nucleophilic Compounds and Detoxifying Enzymes (Vinyl Carbamate Epoxide와 2`-(4-Nitrophenoxy)oxirane으로 유발된 돌연변이에 대한 친핵성 물질 및 해독작용 효소에 의한 억제)

  • 박광균;이자현;김혜원;김종우;김윤수
    • Environmental Mutagens and Carcinogens
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    • v.17 no.2
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    • pp.97-108
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    • 1997
  • The drugs or xenobiotics introduced to the body, are detoxified through the process of biotransformation in the body. In this process, most of the insoluble compounds become more polar, soluble and easily excretable. But, parts of introduced materials are metabolized to highly reactive electrophilic carcinogens through activation pathways. These metabolites are toxic and can react with DNA, RNA and proteins which are nucleophilic compounds. The objective of this study is to illustrate the aleactivation pathways of two highly reactive epoxide compounds, vinyl carbamate epoxide (VCO) and 2'-(4-nitrophenoxy)oxirane (NPO). They are the ultimate electrophilic carcinogens of ethyl carbamate(urethane) and 4-nitrophenyl vinyl ether, respectively. In this research, we studied the inhibition of the mutagenic activities of VCO or NPO by nuchieophiles [glutahione(GSH) and N-acetylcysteine(NAC)], detoxifying enzymes[epoxide hydrolase and glutathione-S-transferase(GST)] and intracellular organelles (microsomes and cytosol). In addition we also tested the suppression of DNA adducts formation by GSH and NAC. The results are summerized as follow. 1. The microsomes and cytosol which contain epoxide hydrolase and GST, respectively, decreased the mutagenicity of VCO (74% and 95%, respecfivel), and NPO (35% and 93%, respectively). The nucleophilic GSH and NAC decreased the mutagenicity by 86% (VCO) and 80% (NPO), 76% (VCO) and 40% (NPO), respectively. 2. The purified epoxide hydrolase decreased the mutagenicity of two epoxides in a dose-dependent manner, and GSH also decreased the mutagenicity in the presence of GST. 3. Formation of two DNA adducts, 7-(2'-oxoethyi)guanine (OEG) and N2,3-ethenoguanine(EG), were compared in the presence of calf thymus DNA and epoxide (VCO or NPO) in vitro system. The amounts of DNA adducts were decreased in the presence of GSH (25% and 29% in VCO, 32% and 29% in NPO), and NAC (14% and 16% in VCO, 21% and 11% in NPO), respectively. From these results, it is concluded that the ultimate carcinogenic metabolites, VCO and NPO, can be made in the body, but much of them may be inactivated and detoxified by the nucleophilic GSH, NAC and detoxifying enzymes (epoxide hydrolase and GST). Therefore, by these mechanism, the formation of DNA adducts and mutagenic activities of these two epoxides may be lowered in vivo.

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Comparison of biological activity according to extracting solvents of four Acanthopanax root bark (추출 용매에 따른 오갈피속 근피의 생리활성 기능 탐색 및 비교)

  • Kim, Sung-Kyoung;Kim, Young-Gil;Lee, Mi-Kyoung;Han, Jong-Soo;Lee, Jin-Ha;Lee, Hyeon-Yong
    • Korean Journal of Medicinal Crop Science
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    • v.8 no.1
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    • pp.21-28
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    • 2000
  • The biological activities of water, ethanol and 50% ethanol extracts from Acanthopanax root bark were compared. 94% of Hep3B cell growth was inhibited by adding 1.0g/L of 50% ethanol extracts from A. senticosus root bark. It was also showed that above 90% of A549 cell growth was inhibited by adding 1.0g/L of 50% ethanol extracts. The 50% ethanol extracts of A. sessiliflorum root bark showed that the extracts selectivity were from 1.5 to 3.4 by adding all samples. For screening immunomodulating activities, Jurkat(T-cell) was showed that the cell growth and viability were more increased and activited 275% by adding the 50% ethanol extracts from A. senticosus root bark. The result of anti-mutagenicity of 50% ethanol extracts of A. senticosus root bark was most effective than any other samples. The enhancement of glutathione-S-transferase activity was increased 241% by adding 1.0g/L 1 : 1 extracts of A. senticosus root bark. 72% of oxidation was inhibited by adding 1.0g/L of 50% ethanol extracts from A. senticosus root bark.

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Antioxidant Enzyme Activities in Tissues of Papilio xuthus during Pupal Stage (호랑나비의 용기 동안 조직 내 항산화 효소의 활성)

  • Shin, Myung-Ja;Kim, Kyoung-Keun;Lim, Jae- Hwan;Jeong, Hyung-Jin;Seo, Eul-Won
    • Journal of Life Science
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    • v.19 no.2
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    • pp.228-233
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    • 2009
  • The purpose of this study is to evaluate the activities of five different antioxidant enzymes in various tissues of Papilio xuthus during pupal stage. Superoxide dismutase (SOD) activity in haemolymph was the highest just after pupation and then decreased gradually until 7 days after pupation but the activity in other tissue was constant during metamorphosis. This result indicates that primary antioxidant process of reactive oxygen species proceed in haemolymph. Catalase (CAT) activity in studied tissues was also the highest just after pupation and its relative activity was also high during pupal stage, suggesting that CAT is the primary enzyme in catalysis of hydrogen peroxide. Glutathion peroxidase (GPX) activity was constant and its relative activity was very low in all tested tissues. Glutathione S-transferase (GST) activity in haemolymph was high at 3 days and 5 days after pupation, and the activity in fat body was the highest at the 1 day after pupation and then decreased gradually for 7 days after pupation. Glutathion reductase (GR) activity in haemolymph and fat body was high at 1 day after pupation, but relatively low GR activity was detected in the rest tissues. Based on these results, GST activity was higher than that of GPX and GR, and it is also believed that GST was more involved in reduction process through lipid peroxidation than GPX.

Antioxidant Effects of Sesamin and Sesamolin in Streptozotocin-induced Diabetes Mellitus Rat (Streptozotocin유발 당뇨쥐에서 세사민과 세사몰린의 항산화효과)

  • 성하정;강명화;정혜경;송은승;정미혜
    • Journal of Food Hygiene and Safety
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    • v.16 no.4
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    • pp.349-354
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    • 2001
  • Oxidative stress is believed to play an important role in the development of vascular complications associated with diabetes mellitus. We examined the antioxidative effect of sesamin and sesamolin on the preventing the development of insulin dependent diabetes mellitus using streptozotocin-induced Spraque Dawley diabetic rats. From 48 hours after injection of streptozotocin (60 mg/kg body weight), a portion of diabetic rats were fed with 0.2% sesamin and sesamolin containing diet for 3 weeks. There were significant differences of blood glucose and kidney weight between diabetic ports and control. Sesamin and sesamolin increased glutathione-S-transferase activity in kidney. The concentration of the thiobarbituric acid-reactive substances in the serum, liver, and kidney of diabetic rats administered sesamin and sesamolin decreased significantly as compared with that of the non-treated diabetic group. Dietary sesamin and sesamolin suppressed the oxidative stress in the diabetic rats. These results demonstrated that sesamin and sesamolin are potential and effective antioxidants that can protect the complications associated with diabetes.

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Modulated Gene Expression of Toxoplasma gondii Infected Retinal Pigment Epithelial Cell Line (ARPE-19) via PI3K/Akt or mTOR Signal Pathway

  • Zhou, Wei;Quan, Juan-Hua;Gao, Fei-Fei;Ismail, Hassan Ahmed Hassan Ahmed;Lee, Young-Ha;Cha, Guang-Ho
    • Parasites, Hosts and Diseases
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    • v.56 no.2
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    • pp.135-145
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    • 2018
  • Due to the critical location and physiological activities of the retinal pigment epithelial (RPE) cell, it is constantly subjected to contact with various infectious agents and inflammatory mediators. However, little is known about the signaling events in RPE involved in Toxoplasma gondii infection and development. The aim of the study is to screen the host mRNA transcriptional change of 3 inflammation-related gene categories, PI3K/Akt pathway regulatory components, blood vessel development factors and ROS regulators, to prove that PI3K/Akt or mTOR signaling pathway play an essential role in regulating the selected inflammation-related genes. The selected genes include PH domain and leucine- rich-repeat protein phosphatases (PHLPP), casein kinase2 (CK2), vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), glutamate-cysteine ligase (GCL), glutathione S-transferase (GST), and NAD(P)H: quinone oxidoreductase (NQO1). Using reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), we found that T. gondii up-regulates PHLPP2, $CK2{\beta}$, VEGF, GCL, GST and NQO1 gene expression levels, but down-regulates PHLPP1 and PEDF mRNA transcription levels. PI3K inhibition and mTOR inhibition by specific inhibitors showed that most of these host gene expression patterns were due to activation of PI3K/Akt or mTOR pathways with some exceptional cases. Taken together, our results reveal a new molecular mechanism of these gene expression change dependent on PI3K/Akt or mTOR pathways and highlight more systematical insight of how an intracellular T. gondii can manipulate host genes to avoid host defense.

The effects of Injinhotang-sihosogantang-gagambang on liver injury (인진호탕합시호소간탕가감방(茵陳蒿湯合柴胡疏肝湯加減方)이 간손상(肝損傷)에 미치는 영향(影響))

  • Kim Tae-Sik;Kang Jae-Chun
    • Journal of Society of Preventive Korean Medicine
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    • v.3 no.2
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    • pp.183-210
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    • 1999
  • In order to investigate the protective effect of Injinhotanghapsihosogantang-gagambang on the liver injury of rats induced by $CCl_4$ and d-galactosamine, the serum transaminase(GOT&GPT) alkaline phosphatase(ALP), lactic dehydrogenase(LDH) for enzyme activities, triglyceride for serum component, liver weight and glutathione S-transferase(GST), Superoxide dimutase(SOD) were measured. All animals were divided into 5 groups, those were normal group(untreated), control group(treated with vehicle 0.9% Saline solution), sample I group(10mg/kg administrated), sample II group(30mg/kg administrated), Silymarin 200 administrated group. The results were as follows: 1. The inhibitory effects of the serum GOT activities in rats induced by $CCl_4$ were noted in both sample I (p<0.001) and sample II group(p<0.001). In serum GPT activities, sample I (p<0.01) and sample II group(p<0.01). 2. The inhibitory effects of the serum LDH activities in rats induced by $CCl_4$ were noted in both sample I (p<0.001) and sample II group(p<0.001). 3. The increased effects of the serum ALP activities in rats induced by $CCl_4$ were not recognized. 4. The inhibitory effects of the serum triglyceride content level in rats induced by $CCl_4$ were inhibited in only sample II group(p<0.05). 5. The increased effects of the liver weight level in rats induced by $CCl_4$ were inhibited in both sample I (p<0.05) and sample II group(p<0.05). 6. The inhibitory effects of the GST activities in rats induced by $CCl_4$ were not recognized. In SOD activities, both sample I (p<0.05) and sample II group(p<0.001) showed the inthbitory effects. 7. The inhibitory effects of in the serum GOT, GPT activities in rats induced by d-galactosamine were not recognized. 8. The increases of the serum LDH level in rats induced by d-galactosamine were noted in both sample I (p<0.01) and sample II group(p<0.001). 9. The inhibitory of the serum triglyceride content level in rats induced d-galactosamine were noted in only sample II group(p<0.05). According to the above results, it is considered that Injinhotanghapsihosogantang-gagambang has protective effect against liver injury in rats induced by $CCl_4$ and d-galactosamine.

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