• Title/Summary/Keyword: glutathione transferase

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Mechanisms of Parathion Resistance in a Ethyl Fenitrothion-Selected Yumenoshima III Strain of House Flies (페니트로치온 도태 Yumenoshima 저항성 집파리에 있어서의 파라치온 저항성 메카니즘)

  • ;;Toshio SHONO
    • Korean journal of applied entomology
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    • v.35 no.3
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    • pp.254-259
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    • 1996
  • The biochemical factors responsible for parathion resistance in a ethyl fenitrothion-selected Yumenoshima I11 (EF-30) strain of the housefly were examined. Great difference (167-fold) in the Iso was observed between the resistant EF-30 (R) and susceptible SRS (S) strains in vitro, suggesting that altered acetylcholinesterase (AChE) in the housefly strain was an important factor in the resistance. The in vitro degradative activity of parathion and paraoxon in both strains was associated with the microsomal and soluble fractions and required NADPH and reduced glutahione (GSH), respectively. The R strain possessed higher activity for GSH S-transferase than the S strain, and this enzyme appears to be important in the resistance mechanism. The R strain was highly resistant to parathion (101,487-fold), but substitution of the methoxy group for ethoxy group decreased the resistance level (25,914-fold) and parathion could be a substrate of GSH S-transferase. It is concluded that the combination of some factors (altered AChE, and enhanced activity of cytochrome P450 dependent monooxygenase and GSH S-transferase) could be sufficient to account for the extremely high level of resistance to parathion and parathion-methyl, although a possible involvement of other factor(s) can not be excluded.

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Protective Mechanism of Salidroside Isolated from Acer termentosum Max on Cyclosporine-Induced Nephrotoxicity in Rats (흰쥐에서 Cyclosporine 유도가 산겨릅나무에서 분리한 salidroside의 신독성 경감기전에 관한 효과)

  • Kim, Sung-Hoon;Park, Hee-Juhn;Choi, Jong-Won
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.1
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    • pp.166-173
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    • 2009
  • Cyclosporine(CsA) is an immunosupressant drug widely used in post-allogeneic organ transplant to reduce the activity of the patient's immune system and so the risk of organ rejection. It has been studied in transplants of skin, heart, kidney, liver, lung, pancreas, bone marrow and small intestine. Initially isolated from a Norwegian soil sample, Both kidney and liver dysfunction are prominent side effects of CsA. The present study was designed to determine the possible protective effect of salidroside(Sal) isolated from the BuOH extract of Acer termentosum Max against oxidative damage in CsA-treated(50 mg/kg, ip) nephrotoxicity rats. Results showed oral administration of methanol and butanol extact of Acer termentosum Max(200 mg/kg, po) significantly reduced activities of marker enzymes(BUN, Creatinine) and LDH activity in serum to CsA induced experimental kidney injured rats. And significantly decrcease of protein amount level in urine and activities of free radical formation enzyme were significantly improved by the treatment of Sal. And significantly decrcease of MDA level in kidney and activities of calalase, glutathione peroxidation and SOD were significantly improved by the treatment of Sal(20 mg/kg, po). But glutathione concentration and glutathione S-transferase actitity was not affected. Results of this study revealed that Sal could afford a significant protection in the alleviation of CsA-induced nephrotoxicity injury.

An Updated Pooled Analysis of Glutathione S-transferase Genotype Polymorphisms and Risk of Adult Gliomas

  • Yao, Lei;Ji, Guixiang;Gu, Aihua;Zhao, Peng;Liu, Ning
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.1
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    • pp.157-163
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    • 2012
  • Objective: Glutathione S-transferases (GSTs) are multifunctional enzymes that play a crucial role in the detoxification of both the endogenous products of oxidative stress and exogenous carcinogens. Recent studies investigating the association between genetic polymorphisms in GSTs and the risk of adult brain tumors have reported conflicting results. The rationale of this pooled analysis was to determine whether the presence of a GST variant increases adult glioma susceptibility by combining data from multiple studies. Methods: In our meta-analysis, 12 studies were identified by a search of the MEDLINE, HIGHWIRE, SCIENCEDIRECT and EMBASE databases. Of those 12, 11 evaluated GSTM1, nine evaluated GSTT1 and seven evaluated GSTP1 Ile105Val. Between-study heterogeneity was assessed using ${\chi}^2$-based Q statistic and the $I^2$ statistic. Crude odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to estimate the association between GSTM1, GSTT1 and GSTP1 polymorphisms and the risk of adult gliomas. Results: The quantitative synthesis showed no significant evidence to indicate an association exists between the presence of a GSTM1, GSTT1 or GSTP1 Ile105Val haplotype polymorphism and the risk of adult gliomas (OR, 1.008, 1.246, 1.061 respectively; 95% CI, 0.901-1.129, 0.963-1.611, 0.653-1.724 respectively). Conclusions: Overall, this study did not suggest any strong relationship between GST variants or related enzyme polymorphisms and an increased risk of adult gliomas. Some caveats include absence of specific raw information on ethnic groups or smoking history on glioma cases in published articles; therefore, well-designed studies with a clear stratified analysis on potential confounding factors are needed to confirm these results.

Protein kinase CK2 activates Nrf2 via autophagic degradation of Keap1 and activation of AMPK in human cancer cells

  • Jang, Da Eun;Song, Junbin;Park, Jeong-Woo;Yoon, Soo-Hyun;Bae, Young-Seuk
    • BMB Reports
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    • v.53 no.5
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    • pp.272-277
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    • 2020
  • Protein kinase CK2 downregulation induces premature senescence in various human cell types via activation of the reactive oxygen species (ROS)-p53-p21Cip1/WAF1 pathway. The transcription factor "nuclear factor erythroid 2-related factor 2" (Nrf2) plays an important role in maintaining intracellular redox homeostasis. In this study, Nrf2 overexpression attenuated CK2 downregulation-induced ROS production and senescence markers including SA-β-gal staining and activation of p53-p21Cip1/WAF1 in human breast (MCF-7) and colon (HCT116) cancer cells. CK2 downregulation reduced the transcription of Nrf2 target genes, such as glutathione S-transferase, glutathione peroxidase 2, and glutathione reductase 1. Furthermore, CK2 downregulation destabilized Nrf2 protein via inhibiting autophagic degradation of Kelch-like ECH-associated protein 1 (Keap1). Finally, CK2 downregulation decreased the nuclear import of Nrf2 by deactivating AMP-activated protein kinase (AMPK). Collectively, our data suggest that both Keap1 stabilization and AMPK inactivation are associated with decreased activity of Nrf2 in CK2 downregulation-induced cellular senescence.

Aristolochia ringens extract ameliorates oxidative stress and dyslipidaemia associated with streptozotocin-induced hyperglycaemia in rats

  • Sulyman, Abdulhakeem Olarewaju;Akolade, Jubril Olayinka;Aladodo, Raliat Abimbola;Ibrahim, Rasheed Bolaji;Na'Allah, Asiat;Abdulazeez, Azeemat Titilola
    • CELLMED
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    • v.8 no.3
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    • pp.12.1-12.7
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    • 2018
  • The study was designed to assess antioxidant and antidyslipidaemic effects of terpenoid-rich extract from the root of Aristolochia ringens V. Hyperglycemia-induced oxidative stress and dyslipidemia were established in rats by single intraperitoneal administration of 65 mg/kg bw streptozotocin. Based on therapeutic dose determined in previous study, streptozotocin-induced rats were orally administered with 75 and 150 mg/Kg bw of A. ringens extract for 14 days. Total protein, serum lipid profiles and biomarkers of oxidative stress in liver and kidney of the experimental rats were determined. Atherogenic and cardiovascular disease risk indices were computed. Streptozotocin-induced hyperglycaemia significantly (p < 0.05) decreased activities of superoxide dismutase, catalase and glutathione transferase as well as the amount of reduced glutathione in both tissues indicating oxidative stress induced kidney and liver injury due to glucotoxicity. In comparison to non-treated hyperglycaemic rats, activities of the antioxidant enzymes and concentration of glutathione-H were significantly (p < 0.0001) increased, whereas malondialdehyde was reduced in the tissues of rats treated with both 75 and 150 mg/Kg bw of the extract. The extract also caused significant (p < 0.001) reduction in elevated levels of total cholesterol, triglycerides and low density lipoprotein-cholesterol levels, whereas concentration of the attenuated high density lipoprotein-cholesterol was increased in serum of the treated rats. Reduced atherogenic and cardiac risk indices were projected for the A. ringens extract-treated groups. Results from this study showed that extract from A. ringens root was rich in terpenoids and may reduce risks of complications associated with hyperglycemia-induced oxidative stress and dyslipidemia.

Rubus coreanus Extract Attenuates Acetaminophen Induced Hepatotoxicity; Involvement of Cytochrome P450 3A4

  • Lee, Young-Ik;Whang, Kyung-Eun;Cho, Jin-Sook;Ahn, Byung-Min;Lee, Sang-Bum;Dong, Mi-Sook;Kim, Tae-Hyun
    • Biomolecules & Therapeutics
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    • v.17 no.4
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    • pp.455-460
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    • 2009
  • Foods of plant origin, especially fruits and vegetables, have attracted attention because of their potential benefits to human health. In this report, Rubi Fructus (RF), the dried unripe fruit of Rubus coreanus Miq (Rosaceae) and ellagic acid (EA) purified from RF were used to test their potential hepatoprotective effect against acetaminophen (AAP)-induced hepatotoxicity in rats. RF extract (RFext) and EA reduced the elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in serum and the content of lipid peroxide in liver by AAP administration, while the increment of the cellular glutathione (GSH) content and the induction of glutathione S-transferase (GST) and glutathione peroxidase (GSH-PX) which were decreased by AAP administration. RFext and EA from RFext did not affect the two major form of cytochrome P450s, cytochrome P450 2E1 (CYP2E1) and cytochrome P450 1A2 (CYP1A2), but downregulated the cytochrome P450 3A4 (CYP3A4) related to the conversion of AAP to N-acetyl-P-benzoquinone imine (NAPQI). These results suggest that RFext and EA from RF exhibit a hepatoprotective effect not only by increasing antioxidant activities but also by down-regulating CYP3A4 in the AAP-intoxicated rat.

Effects of Salicornia Herbacea L. Supplementation on Antioxidative Enzyme Activities in Streptozotocin-Induced Diabetic Rats (함초 첨가식이가 당뇨유발 흰쥐의 항산화효소 활성에 미치는 영향)

  • Kim, Myung-Wha
    • Journal of Nutrition and Health
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    • v.41 no.7
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    • pp.583-593
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    • 2008
  • This study was designed to examine the effects of Salicornia herbacea L. (glasswort: GW) on hepatic antioxidative enzyme activities in diabetic rats. Diabetes mellitus was induced in male Sprague-Dawley rats weighing 200-220g by an injection of streptozotocin (STZ) dissolved in a citrate buffer into the tail vein at a dose of 45 mg/kg of body weight. Sprague-Dawley rats were fed an AIN-93 recommended diet and the experimental groups were fed a modified diet containing 10% and 20% of glasswort powder for 4 weeks. The experimental groups were divided into 6 groups which consisted of normal (N)-control group, N-GW 10% and N-GW 20% treated groups, STZ-control, STZ-GW 10% and STZ-GW 20% treated groups. The activities of Xanthine oxidase (XOD), glutathione- S-transferase (GST), glutathione peroxidase (GPX), glutathione reductase (GR), superoxide dismutase (SOD) and CAT (CAT) were measured in the homogenates of liver. The activity of CAT was lower in the supplementary group with glasswort compare to the STZcontrol group but it was not significantly different. The activity of SOD was not significant in all of experimental groups. The activity of GR was significantly increased in the normal supplementary group with glasswort, and GPX activity was significantly increased in STZ-GW 10% group compare to the STZ-control group. The activity of XOD was significantly decreased in the all of supplementary groups with glasswort. The activity of GST was significantly increased in the N-GW 20% group and it was significantly decreased in the STZ-GW 20% group. These results show that the supplementation of glasswort may have favorable influence on antioxidative status in diabetic rats and it may be useful for the diabetic complications as functional food.

Antioxidant Effects of Ginseng Powder on Liver of $Benzo({\alpha})Pyrene-treated$ Mice (벤조피렌을 투여한 마우스 간에서 인삼 분말의 항산화 효과)

  • Kim, Hyun-Jeong;Hwangbo, Mi-Hyang;Lee, Ji-Won;Im, Hyo-Gun;Lee, In-Seon
    • Korean Journal of Food Science and Technology
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    • v.39 no.2
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    • pp.217-221
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    • 2007
  • In order to determine the effects of ginseng powder on the antioxidant enzyme activities of hepatotoxicity in $benzo({\alpha})pyrene[B({\alpha})P]-treated$ mice, the mice were divided into 5 groups. Ginseng powder was injected intraperitoneally once a day for 5 successive days, followed by the administration of $B({\alpha})P$ treatment on the fifth day. We also evaluated the relationship existing between lipid peroxidation and ginseng powder on oxidative stress. The increased activities of superoxide dismutase, catalase, and glutathione peroxidase observed following $B({\alpha})P-treatment$ were reduced as the result of ginseng powder treatment. Whereas, the glutathione content and glutathione S-transferase activity depleted by $B({\alpha})P$ were increased significantly, but the $B({\alpha})P-associated$ elevation of cytochrome P-450 activities and lipid peroxide content were reduced as the result of ginseng powder treatment. These results indicate that ginseng powder may exert a protective effect against $B({\alpha})P-induced$ hepatotoxicity in mice.

Antioxidant mechanism of black garlic extract involving nuclear factor erythroid 2-like factor 2 pathway

  • Ha, Ae Wha;Kim, Woo Kyoung
    • Nutrition Research and Practice
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    • v.11 no.3
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    • pp.206-213
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    • 2017
  • BACKGROUN/OBJECTIVES: Although studies have revealed that black garlic is a potent antioxidant, its antioxidant mechanism remains unclear. The objective of this study was to determine black garlic's antioxidant activities and possible antioxidant mechanisms related to nuclear factor erythroid 2-like factor 2 (Nrf2)-Keap1 complex. METHODS/MATERIALS: After four weeks of feeding rats with a normal fat diet (NF), a high-fat diet (HF), a high-fat diet with 0.5% black garlic extract (HF+BGE 0.5), a high-fat diet with 1.0% black garlic extract (HF+BGE 1.0), or a high-fat diet with 1.5% black garlic extract (HF+BGE 1.5), plasma concentrations of glucose, insulin,homeostatic model assessment of insulin resistance (HOMA-IR) were determined. As oxidative stress indices, plasma concentrations of thiobarbituric acid reactive substances (TBARS) and 8-isoprostaglandin $F2{\alpha}$ (8-iso-PGF) were determined. To measure antioxidant capacities, plasma total antioxidant capacity (TAC) and activities of antioxidant enzymes in plasma and liver were determined. The mRNA expression levels of antioxidant related proteins such as Nrf2, NAD(P)H: quinone-oxidoreductase-1 (NQO1), heme oxygenase-1 (HO-1), glutathione reductase (GR), and glutathione S-transferase alpha 2 (GSTA2) were examined. RESULTS: Plasma glucose level, plasma insulin level, and HOMA-IR in black garlic supplemented groups were significantly (P < 0.05) lower than those in the HF group without dose-dependent effect. Plasma TBARS concentration and TAC in the HF+BGE 1.5 group were significantly decreased compared to those of the HF group. The activities of catalase and glutathione peroxidase were significantly (P < 0.05) increased in the HF+BGE 1.0 and HF+BGE 1.5 groups compared to those of the HF group. The mRNA expression levels of hepatic Nrf2, NQO1, HO-1, and GSTA2 were significantly (P < 0.05) increased in the HF with BGE groups compared to those in the HF group. CONCLUSIONS: The improvements of blood glucose homeostasis and antioxidant systems in rats fed with black garlic extract were related to mRNA expression levels of Nrf2 related genes.

The Expression and Functional Analysis of Recombinant Alcohol Dehydrogenase (재조합 alcohol dehydrogenase의 발현 및 기능분석)

  • Kong, Kwang-Hoon;Shim, Eun-Jung;Park, Hee-Joong;Kim, Eun-Ho;Cho, Sung-Hye;Park, Sung-Woo;Kim, Young-Mann
    • Analytical Science and Technology
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    • v.12 no.6
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    • pp.565-570
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    • 1999
  • The alcohol dehydrogenase (ADH) gene from Bacillus stearothermopilus was amplified by the polymerase chain reaction. The amplified DNA was inserted into the expression vector pGEX-KG, and expressed it as a fusion protein with glutathione S-transferase (GST) in E. coli. The recombinant ADH was produced by induction with 1 mM isopropyl-${\beta}$-D-thiogalactopyranoside at $37^{\circ}C$ and purified by glutathione affinity chromatography. The recombinant ADH exhibited high substrate specificity for ethanol. The activity of the recombinant ADH proceeded optimally at pH 9.0 and $70^{\circ}C$. The recombinant ADH was highly stable against high temperature. This thermostable alcohol dehydrogenase can be used for the enzymatic determination of alcohol and for the industrial production of alcohol.

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