• Title/Summary/Keyword: detoxification enzymes

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In vitro and In vivo Responses of Hepatic Xenobiotic Metabolizing Enzymes in Flounder (Paralichthys olivaceus) Exposed to Formalin (Formalin에 노출시킨 넙치 (Paralichthys olivaceus) 간장 약물대사효소의 in vivo 및 in vitro 반응)

  • Lee, Ji-Seon;Ha, Jin-Hwan;Lee, Kyoung-Seon;Jeon, Joong-Kyun
    • Korean Journal of Environmental Biology
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    • v.24 no.2 s.62
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    • pp.195-200
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    • 2006
  • The response of hepatic mixed function oxygenase (MFO) system was investigated in olive flounder exposed to formalin. Hepatic microsome of olive flounder incubated in vitro with formalin demonstrated the induction of cytochrome P450 (CYP), ethoxyresorufin deethylase (EROD), cytochrome P450 reductase (P450R) and cytochrome b5 reductase (b5R) activity. In addition, olive flounder was exposed to 100, 300 and 500 ppm of formalin for 1 h and then transferred to a flow-through type of 1000 L aquarium. Hepatic MFO enzyme activity was determined for 72 h. As the result, hepatic CYP, P450R and EROD activities increased following exposure of formalin, but b5R and GST showed no significant change. These results imply that CYP and P450R can be considered as main hepatic enzymes involving in detoxification of formalin.

Effect of Cnidii Rhizoma Water Extract on Chemopreventive Enzymes for Hepatocarcinoma (천궁 물추출물이 간암예방효소계에 미치는 영향)

  • Shon, Yun-Hee;Kim, Han-Gyu;Nam, Kyung-Soo
    • Korean Journal of Pharmacognosy
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    • v.34 no.4 s.135
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    • pp.297-302
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    • 2003
  • Cnidii Rhizoma water extract (CRW) was tested for liver cancer chemopreventive potential by measuring the inhibition of phase I enzyme and benzo[a]pyrene-DNA adduct formation and induction of phase II detoxification enzymes. There was 17.0% inhibition in the activity of cytochrome P450 1A1 enzyme with the treatment of 150 mg/ml CRW. At concentration of 30 mg/ml CRW, the binding of $[^3H]B[a]P$ metablites to DNA of NCTC-clone 1469 cell was inhibited by 33.3%. CRW was potent inducer of quinone reductase (QR) and glutathione S-transferase (GST) activities in cultured murine hepatoma Hepalc1c7 cells. However, hepatic glutathione (GSH) level was not influenced by CRW. These findings suggest that CRW has chemopreventive potential of liver cancer by inhibiting cytochrome P450 1A1 activity and benzo[a]pyrene-DNA adduct formation and inducing QR and GST activities.

Detoxification Mechanism and Isoenzyme Pattern Changes against Cadmium in Rhizopus oryzae (Rhizopus oryzae의 카드뮴 해독기작과 이에 관련된 동위효소의 변화 양상)

  • Lee, Ki-Sung;Kim, Young-Ho;Park, Young-Sik;Park, Yong-Keun
    • The Korean Journal of Mycology
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    • v.23 no.1 s.72
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    • pp.86-91
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    • 1995
  • Isoenzymatic analysis related with cadmium adaptation and detoxifying mechanism were carried out upon Rhizopus oryzae. When cadmium was added into R. oryzae culture, activities of malate dehydrogenase (MDH) and glucose phosphate isomerase (GPI) related with carbohydrate metabolizing pathways were stimulated. Novel isoenzyme CAT-2 related with removing intracellular toxic peroxides, was induced lately and derepressed very highly. On the other hand, lactate-catabolizing enzymes such as lactate dehydrogenase (LDH) and alcohol dehydrogenase (ADH) were repressed. These results strongly suggest that, under cadmium stress, much of derepression of enzymes relating with central metabolism such as TCA cycle that produces high yield of energy and relating with removal of toxic peroxides should be necessary.

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Alteration of mitochondrial DNA content modulates antioxidant enzyme expressions and oxidative stress in myoblasts

  • Min, Kyung-Ho;Lee, Wan
    • The Korean Journal of Physiology and Pharmacology
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    • v.23 no.6
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    • pp.519-528
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    • 2019
  • Mitochondrial dysfunction is closely associated with reactive oxygen species (ROS) generation and oxidative stress in cells. On the other hand, modulation of the cellular antioxidant defense system by changes in the mitochondrial DNA (mtDNA) content is largely unknown. To determine the relationship between the cellular mtDNA content and defense system against oxidative stress, this study examined a set of myoblasts containing a depleted or reverted mtDNA content. A change in the cellular mtDNA content modulated the expression of antioxidant enzymes in myoblasts. In particular, the expression and activity of glutathione peroxidase (GPx) and catalase were inversely correlated with the mtDNA content in myoblasts. The depletion of mtDNA decreased both the reduced glutathione (GSH) and oxidized glutathione (GSSG) slightly, whereas the cellular redox status, as assessed by the GSH/GSSG ratio, was similar to that of the control. Interestingly, the steady-state level of the intracellular ROS, which depends on the reciprocal actions between ROS generation and detoxification, was reduced significantly and the lethality induced by $H_2O_2$ was alleviated by mtDNA depletion in myoblasts. Therefore, these results suggest that the ROS homeostasis and antioxidant enzymes are modulated by the cellular mtDNA content and that the increased expression and activity of GPx and catalase through the depletion of mtDNA are closely associated with an alleviation of the oxidative stress in myoblasts.

Response of Antioxidative Enzymes of Two Rice Cultivars to Ozone Exposure and Nutrient Supply

  • Lee, Sang-Chul;Hwan, Cho-Jeong;Park, Shin-Young;Son, Tae-Kwon
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.46 no.1
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    • pp.40-46
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    • 2001
  • Ozone ($O_3$)-induced changes in chlorophyll content and specific activities of antioxidant enzymes, such as superoxide dismutase (SOD), ascorbate peroxidase (APX), guaiacol peroxidase (GPX), dehydroascorbate reductase (DHAR) and glutathione reductase (GR) were investigated in two rice cultivars (Oryza sativa L.) grown under variable nutrient treatments. For this study, two rice cultivars of Ilpumbyeo (IL) and Keumobyeo#l (KM), which were known as resistant and susceptible to $O_3$, respectively, were exposed to $O_3$at 0.15ppm for 30 days and investigated with 10 days interval. The available nutrient regimes were varied by doubling the supply of nitrogen (N), phosphorus (P) and potassium (K) Within a basic fertilizer status (N, P, K; 15, 12, 12kg/l0a$^{-1}$ ). In both cultivars and at all nutrient status, chlorophyll content in $O_3$-treated plants decreased with prolonged treatment period, although higher N, P and K supply with $O_3$ treatment alleviated the decrease in chlorophyll content. The activities of almost all enzymes investigated for this study were decreased during initial stages of $O_3$- exposure except GPX which maintained higher activity throughout the exposure period than the non-treated plant. However, the antioxidant enzymes in $O_3$-treated plants showed almost the same or higher activities on 30 days after $O_3$ - exposure. The most significant changes in activities were observed in GR of the $O_3$-treated leaves. With the prolonged treatment period, the activity of GR at 30 days was increased by 3-8 times compared to those in 10 days. Most of the investigated enzymes showed very similar tendency to $O_3$ treatment in all fertilizer status. There was no observed evidence for enhanced detoxification of $O_3$-derived activated oxygen species in plants grown under higher fertilizer status compared with that in plants grown under basic fertilizer status. The increase in the activities of SOD, APX and GR in rice leaves by relatively long-term treatment with $O_3$ at low concentration is considered to indicate that the plant became adapted to the $O_3$ stress and the protection system increased its capacity to scavenge toxic oxygen species. Our results in two rice cultivars indicated that there was little difference in the activities of antioxidant enzymes between IL and KM, which were known as resistant and susceptible cultivar to $O_3$

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S-(N,N-Diallyldithiocarbamoyl)-N-acetylcysteine: Synthesis and Biochemical Properties Associated with Chemoprevention (S-(N,N-Diallyldithiocarbamoyl)-N-acetylcysteine의 합성 및 발암억제와 관련된 생화학적 특성)

  • 이병훈
    • Toxicological Research
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    • v.14 no.2
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    • pp.177-181
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    • 1998
  • Dithiocarbamate and mixed disulfide containing allyl functions were designed and synthesized as putative chemopreventive agents, i.e. N,N-diallyldithiocarbamate (DATC) and S-(N,N-diallyldithiocarbamoyl)-N-acetylcysteine (AC-DATC). DATC and AC-DATC were administered and the activities of cytosolic glutathione S-transferase (GST), glutathione reductase (GR) and microsomal N-nitrosodiethylamine (NDEA) deethylase were assayed in order to test the effects of these organosulfur com-pounds on the detoxification and metabolic activation system of NDEA. The amounts of hepatic glutathione (GSH and GSSG) was also determined. The administration of DATC to rats led to an increase in the activity of GR and to an inhibition of CYP2E1-mediated NDEA deethylation. AC-DATC induced the activity of GR and GST, increased the hepatic GSH content and inhibited the rate of NDEA deethylation. The level of GSSG was decreased as a consequence of the increased activity of GR. These effects may contribute to possible antimutagenic and anticarcinogenic action of the dithiocarbamates investigated.

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Identification of Genes for Mycothiol Biosynthesis in Streptomyces coelicolor A3(2)

  • Park Joo-Hong;Cha Chang-Jun;Roe Jung-Hye
    • Journal of Microbiology
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    • v.44 no.1
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    • pp.121-125
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    • 2006
  • Mycothiol is a low molecular weight thiol compound produced by a number of actinomycetes, and has been suggested to serve both anti-oxidative and detoxifying roles. To investigate the metabolism and the role of mycothiol in Streptomyces coelicolor, the biosynthetic genes (mshA, B, C, and D) were predicted based on sequence homology with the mycobacterial genes and confirmed experimentally. Disruption of the mshA, C, and D genes by PCR targeting mutagenesis resulted in no synthesis of mycothiol, whereas the mshB mutation reduced its level to about $10\%$ of the wild type. The results indicate that the mshA, C, and D genes encode non-redundant biosynthetic enzymes, whereas the enzymatic activity of MshB (acetylase) is shared by at least one other gene product, most likely the mca gene product (amidase).

Effects of Extract and Isorhamnetin Glycoside from Brassica juncea on Hepatic Alcohol-Metabolizing Enzyme System in Rats

  • Hur, Jong-Moon;Park, Sang-Hyun;Choi, Jong-Won;Park, Jong-Cheol
    • Natural Product Sciences
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    • v.18 no.3
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    • pp.190-194
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    • 2012
  • The effects of methanol extract of the leaves of Brassica juncea and its major component, isorhamnetin 3-O-${\beta}$-D-glucopyranoside on hepatic alcohol metabolizing enzymes were investigated. The methanol extract and isorhamnetin 3-O-${\beta}$-D-glucopyranoside supplementations increased the activities of microsomal ethanol oxidizing system and aldehyde dehydrogenase in a dose-dependent manner, and had mild effects on the activities of alcohol dehydrogenase and catalase. Isorhamnetin 3-O-${\beta}$-D-glucopyranoside alleviated the adverse effect of ethanol ingestion by enhancing the activities of alcohol oxidizing emzymes, microsomal ethanol oxidizing system and aldehyde dehydrogenase.

Thiol-Based Peroxidases and Ascorbate Peroxidases: Why Plants Rely on Multiple Peroxidase Systems in the Photosynthesizing Chloroplast?

  • Dietz, Karl-Josef
    • Molecules and Cells
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    • v.39 no.1
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    • pp.20-25
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    • 2016
  • Photosynthesis is a highly robust process allowing for rapid adjustment to changing environmental conditions. The efficient acclimation depends on balanced redox metabolism and control of reactive oxygen species release which triggers signaling cascades and potentially detrimental oxidation reactions. Thiol peroxidases of the peroxiredoxin and glutathione peroxidase type, and ascorbate peroxidases are the main peroxide detoxifying enzymes of the chloroplast. They use different electron donors and are linked to distinct redox networks. In addition, the peroxiredoxins serve functions in redox regulation and retrograde signaling. The complexity of plastid peroxidases is discussed in context of suborganellar localization, substrate preference, metabolic coupling, protein abundance, activity regulation, interactions, signaling functions, and the conditional requirement for high antioxidant capacity. Thus the review provides an opinion on the advantage of linking detoxification of peroxides to different enzymatic systems and implementing mechanisms for their inactivation to enforce signal propagation within and from the chloroplast.

Molecular Basis of the KEAP1-NRF2 Signaling Pathway

  • Takafumi Suzuki;Jun Takahashi;Masayuki Yamamoto
    • Molecules and Cells
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    • v.46 no.3
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    • pp.133-141
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    • 2023
  • Transcription factor NRF2 (NF-E2-related factor 2) is a master regulator of cellular responses against environmental stresses. NRF2 induces expression of detoxification and antioxidant enzymes and suppresses inductions of pro-inflammatory cytokine genes. KEAP1 (Kelch-like ECH-associated protein 1) is an adaptor subunit of CULLIN 3 (CUL3)-based E3 ubiquitin ligase. KEAP1 regulates the activity of NRF2 and acts as a sensor for oxidative and electrophilic stresses. NRF2 has been found to be activated in many types of cancers with poor prognosis. Therapeutic strategies to control NRF2-overeactivated cancers have been considered not only by targeting cancer cells with NRF2 inhibitors or NRF2 synthetic lethal chemicals, but also by targeting host defense with NRF2 inducers. Understanding precise molecular mechanisms how the KEAP1-NRF2 system senses and regulates the cellular response is critical to overcome intractable NRF2-activated cancers.