• Title/Summary/Keyword: Antioxidant enzyme genes

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Nrf2 Knockout Mice that Lack Control of Drug Metabolizing and Antioxidant Enzyme Genes - Animals Highly Sensitive to Xenobiotic Toxicity

  • Enomoto, Akiko;Itoh, Ken;Harada, Takanori;Yamamoto, Masayuki
    • Toxicological Research
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    • v.17
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    • pp.299-304
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    • 2001
  • Xenobiotics and their reactive intermediates bind to cellular macromolecules and/or generate oxidative stress. which provoke deleterious effects on the cell function. Induction of xenobiotic-biotrans-forming enzymes and antioxidant molecules is an important defense mechanism against such insults. A group of genes involved in the defense mechanism. e.g. genes encoding glutathione S-transferases. NAD(P)H: quinone oxidoreductase, UDP-glucuronosyltransferase (UDP-GT) and ${\gamma}$-glutamylcysteine synthetase (GGCS). have a common regulatory sequence, Antioxidant or Electrophile Responsive Element (ARE/EpRE). Recently. Nrf2. discovered as a homologue of erythroid transcription factor p45 NF-E2, was shown to bind ARE/EpRE and induce the expression of these defense genes. Mice that lack Nrf2 show low basal levels of expression and/or impaired induction of these genes. which makes the animals highly sensitive to xenobiotic toxicity. Indeed. we show here that nrf2-deficient mice had a higher mortality than did the wild-type mice when exposed to acetaminophen (APAP). Detailed analyses of APAP hepatotoxicity in the nrf2 knockout mice indicate that a large amount of reactive APAP metabolites was generated in the livers due to the impaired basal expression of two detoxifying enzyme genes, UDP-GT (Ugt1a6) and GGCS. while the cytochrome P450 content was unchanged. Thus. the studies using the nrf2 knockout mice clearly demonstrate significance of the expression of Nrf2-regulated enzymes in protection against xenobiotic toxicity.

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Nrf2 and Keap1 Regulation of Antioxidant and Phase II Enzyme Genes

  • Yamamoto, M.
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.05a
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    • pp.24-42
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    • 2002
  • Antioxidant responsive element (ARE) mediates the transcriptional activation of the genes encoding phase II drug metabolizing enzymes and antioxidative stress genes. The ARE consensus sequence shows high similarity to NF-E2 binding sequence, a cisacting erythroid gene regulatory element.(omitted)

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Expression of the Antioxidant Enzyme and Apoptosis Genes in in vitro Maturation lin vitro Fertilization of Porcine Embryos

  • H. Y. Jang;H. S. Kong;Park, K. D.;G. J. Jeon;Lee, H. K.;B. K. Yang
    • Proceedings of the KSAR Conference
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    • 2003.06a
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    • pp.47-47
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    • 2003
  • The present study was conducted to determine the expression of the antioxidant enzyme(CuZn-SOD, Mn-SOD and GPX and apoptosis gene(caspase-3) for in vitro culture in in vitro maturation and in vitro fertilization(IVM/IVF) embryos in porcine. Porcine embryos derived from IVM/IVF were cultured in NCSU23 medium under 5% $CO_2$ in air at 38.5$^{\circ}C$. The patterns of gene expression for several antioxidant enzyme and apoptosis genes during preimplantion porcine embryo development were examined by the modified semi-quantitative single cell reverse transcriptase- polymerase chain reaction (RT-PCR). Preimplantation porcine embryos produced by IVM/IVF have expressed mRNAs for CuZn-SOD and GPX, whereas transcripts for Mn-SOD have not detected at any developmental stages. Expression of caspase-3 mRNA was detected at 2 cell, 8 cell, 16 cell and morula stages. The fas ligand transcripts were detected in porcine blastocyst. These results suggest that various antioxidant enzymes and apoptosis genes play crucial roles in in vitro culture of porcine IVM/IVF embryos.

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Effect of Genistein on Activity and Expression of Antioxidant Enzyme in Hamster ovary cells (Genistein이 햄스터 난소세포의 항산화효소활성과 발현에 미치는 영향)

  • Kim, Min-Hye;Kim, An-Keun
    • YAKHAK HOEJI
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    • v.51 no.1
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    • pp.75-82
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    • 2007
  • Reactive oxygen species (ROS) are produced in the metabolic process of oxygen in cells. The superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in cells systemize the antioxidant enzymes to control the oxidative stress. Genistein is one of the isoflavonoids, and its role in controlling cellular oxidative stress is presently the active issue at question. In this study; we analyzed genistein-induced survival rates of the CHO-K1 cells, activities of antioxidant enzymes, ROS levels, and expression levels of antioxidant enzyme genes in order to investigate the effect of genistein on cellular ROS production and antioxidative systems in CHO-K1 cells. As results, the survival rate of cells was decreased as the dose of genistein increases (12.5${\sim}$200 ${\mu}$M). Genistein increased cellular ROS levels, while it reduced total SOD activities and the expression of CuZnSOD. In conclusion, we suggest that genistein may induce oxidative stress via down-regulation of SOD.

Molecular cloning of cDNAs encoding antioxidant enzymes in Korean rock bream (Oplegnathus fasciatus)

  • Park, Byul-Nim;Park, Ji-Eun;Kim, Ki-Hong;Kim, Sung-Koo;Nam, Yoon-Kwon
    • Proceedings of the Korean Aquaculture Society Conference
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    • 2003.10a
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    • pp.39-39
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    • 2003
  • Antioxidant enzyme genes play a key role in cell defense against the lethal effects of oxidative stresses in animals and have an essential function which has allowed the evolution of aerobic respiration starting from an ancient form of oxygen-insensitive life. Piscine antioxidant enzymes are also involved in the rapid response to various toxic chemicals as well as many biological stresses, indicating that they could be used as biomarkers for health and aquatic environment. With the purpose for developing fine molecular probing tool to assess the stresses in marine fish, we identified three major antioxidant enzyme genes (superoxide dismutase, catalase and glutathione-S-transferase) from Korean rock bream using expressed sequence tag analysis and/or high density filter screening. Here we report the molecular information on these gene transcripts including complete sequence data and expression profiles.

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Transcriptional Response of Major Antioxidant Enzyme Genes to Heat Stress in Mud Loach (Misgurnus mizolepis) (고온 스트레스에 대한 미꾸라지(Misgurnus mizolepis) 항산화 효소 유전자들의 발현 특징)

  • Cho Young-Sun;Lee Sang-Yoon;Bang In-Chul;Kim Dong-Soo;Nam Yoon-Kwon
    • Journal of Aquaculture
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    • v.19 no.3
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    • pp.157-165
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    • 2006
  • Expression of major antioxidant enzyme (AOE) including Cu/Zn superoxide dismutase (Cu/Zn-SOD), catalase (CAT), glutathione-S-transferase (GST) and 3 glutathione peroxidase isotypes (GPXs) at mRNA levels during heat stress was examined in mud loach (Misgurnus mizolepis) liver. Based on the semi-quantitative RT-PCR, real-time RT-PCR and/or northern dot blot hybridization, the antioxidant enzyme genes were generally up-regulated during elevation of water temperature from $23^{\circ}C$ up to $32^{\circ}C$. GPXs and SOD displayed the most significant elevation of mRNA levels (up to 3 and 2 folds, respectively) while CAT showed the steady-state expression irrespective of thermal conditions. GST represented the relatively moderate response (1.3-fold increase) in its transcription to thermal stress. The transcriptional activation of AOE genes was not significant at the treatment temperature lower than $29^{\circ}C$. Increased mRNA levels of GPX (extracellular form) and SOD genes in the fish exposed to $32^{\circ}C$ was readily detectable 1 day after exposure to heat stress.

Anti-obese related pharmacological effects of standard potato protein extracts on the 45%Kcal high fat diet supplied mice

  • Kang, Su-Jin;Song, Chang-Hyun;Kim, Jong-Kyu;Chun, Yoon-Seok;Han, Chang-Hyun;Lee, Young-Joon;Ku, Sae-Kwang
    • Journal of Society of Preventive Korean Medicine
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    • v.22 no.2
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    • pp.77-107
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    • 2018
  • Objectives : In present study, therefore, possible beneficial pharmacological activities of standard potato protein extracts (SPE) were observed on the mild diabetic obese mice. Methods : After end of 12 weeks of continuous oral administrations of three different dosages of SPE 400, 200 and 100 mg/kg, or metformin 250 mg/kg, analyzed the hepatoprotective, hypolipidemic, hypoglycemic, nephroprotective and anti-obesity effects, separately. In addition, liver antioxidant defense systems were additionally measured with lipid metabolism-related genes expressions and hepatic glucose-regulating enzyme activities for action mechanism. Results : All of diabetes and related complications including obesity were significantly inhibited by treatment of SPE 400, 200 and 100 mg/kg, dose-dependently, and they also dramatically normalized the hepatic lipid peroxidation and depletion of liver endogenous antioxidant defense system, the changes of the hepatic glucose-regulating enzyme activities, also changes of the lipid metabolism-related genes expressions including hepatic $AMPK{\alpha}1$ and $AMPK{\alpha}2$ mRNA expressions, dose-dependently. Especially, SPE 200 mg/kg constantly showed favorable inhibitory activities against type II diabetes and related complications as comparable to those of metformin 250 mg/kg in HFD mice, respectively. Conclusions : The present work demonstrated that SPE 400, 200 and 100 mg/kg showed favorable anti-diabetic and related complications including obesity refinement activities in HFD mice, through AMPK upregulation mediated hepatic glucose enzyme activity and lipid metabolism-related genes expression, antioxidant defense system and pancreatic lipid digestion enzyme modulatory activities.

Cytoprotection Against Oxidative Damage by Nrf2-regulated Genes

  • Kwak, Mi-Kyoung;Kensler, Thomas W.
    • Toxicological Research
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    • v.23 no.3
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    • pp.207-214
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    • 2007
  • Chronic oxidative stress produced by exposure to environmental chemicals or pathophysiological states can lead animals to aging, carcinogenesis and degenerative diseases. Indirect antioxidative mechanisms, in which natural or synthetic agents are used to coordinately induce the expression of cellular antioxidant capacity, have been shown to protect cells and organisms from oxidative damages. Electrophile and free radical detoxifying enzymes, which were originally identified as the products of genes induced by cancer chemopreventive agents, are members of this protective system. The NFE2 family transcription factor Nrf2 was found to govern expression of these detoxifying enzymes, and screening for Nrf2-regulated genes has identified many gene categories involved in maintaining cellular redox potential and protection from oxidative damage as Nrf2 downstream genes. Further, studies using Nrf2-deficient mice revealed that these mutant mice showed more susceptible phenotypes towards exposure to environmental chemicals/carcinogens and in oxidative stress related disease models. With the finding that cancer chemopreventive efficacy of indirect antioxidants (enzyme inducers) is lost in the absence of Nrf2, a central role of Nrf2 in the antioxidative protective system has been firmly established. Promising results from cancer prevention clinical trials using enzyme inducers propose that pharmacological interventions that modulate Nrf2 can be an effective strategy to protect tissues from oxidative damage.

Effects of Antioxidants on the Antioxidant and Apoptosis Genes Expression of IVM/IVF Hanwoo Embryos

  • Jang, H.Y.;Parkm C.K.;Cheong, H.T.;Kim, C.I.;Yim, S.V.;Kim, S.S.;Park, D.H.;Yang, B.K.
    • Proceedings of the KSAR Conference
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    • 2002.06a
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    • pp.69-69
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    • 2002
  • To investigate the effects of two antioxidants, aesculeitin and taurine, expression of apoptosis related genes and antioxidant enzyme gene in preimplantation Hanwoo embryos was determined by modified semi-quantitative single cell RT-PCR. Hanwoo embryos derived from in vitro maturation /in vitro fertilization were cultured in 5% CO₂ and 5% O₂ in CR₁aa medium at 37℃. Aesculeitin and taurine were added to medium at concentration of l㎍/㎖ and 2.5mM, respectively. (omitted)

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