• 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.

• BMB Reports
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• v.38 no.2
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• pp.218-224
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• 2005

Antioxidant enzymes are related to the resistance to various abiotic stresses including salinity. Barley is relatively tolerant to saline stress among crop plants, but little information is available on barley antioxidant enzymes under salinity stress. We investigated temporal and spatial responses of activities and isoform profiles of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), non-specific peroxidase (POX), and glutathione reductase (GR) to saline stress in barley seedlings treated with 200 mM NaCl for 0, 1, 2, 5 days, respectively. In the control plant, hydrogen peroxide content was about 2-fold higher in the root than in the shoot. Under saline stress, hydrogen peroxide content was decreased drastically by 70% at 2 d after NaCl treatment (DAT) in the root. In the leaf, however, the content was remained unchanged by 2 DAT and increased about 14 % at 5 DAT. In general, the activities of antioxidant enzymes were increased in the root and shoot under saline stress. But the increase was more significant and consistent in the root. The activities of SOD, CAT, APX, POX, and GR were increased significantly in the root within 1 DAT, and various elevated levels were maintained by 5 DAT. Among the antioxidant enzymes, CAT activity was increased the most drastically. The significant increase in the activities of SOD, CAT, APX, POX, and GR in the NaCl-stressed barley root was highly correlated with the increased expression of the constitutive isoforms as well as the induced ones. The hydrogen peroxide content in the root was most highly correlated with the CAT activity, indicating an increased role of CAT in hydrogen peroxide detoxification under salinity stress. In addition, the results suggest the significance of temporal and spatial regulation of each antioxidant isoform in determining the competence of the antioxidant capacity under saline stress.

• Food Science and Biotechnology
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• v.17 no.3
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• pp.613-622
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• 2008

Cancer chemopreventive effects can be exerted through the induction of phase II detoxification enzymes and the inhibition of inflammatory responses. In this study, the cancer chemopreventive effects and anti-inflammatory responses of 30 seaweed extracts were examined. The extracts of Dictyota coriacea and Cutleria cylindrica exhibited the high chemoprevention index, having 4.36 and 4.66, respectively. They also activated antioxidant response element at $100\;{\mu}g/mL$ by about 3-fold while did not activate xenobiotic response element. Seven seaweed extracts, Ishige okamurae, Desmarestia ligulata, Desmarestia viridis, Dictyopteris divaricata, D. coriacea, Sargassum horneri, and Sargassum yezoense, showed significant inhibition on nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) production in a dose-dependant manner in $5-20\;{\mu}g/mL$. These seaweed extracts could be used as food materials for cancer chemoprevention. D. coriacea could contain potential chemopreventive agents not only that regulate genes via an ARE-dependent mechanism but also prevent the inflammation through inhibition of NO and $PGE_2$ production.

• Nutrition Research and Practice
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• v.9 no.1
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• pp.49-56
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• 2015

BACKGROUND/OBJECTIVES: Glutathione S-transferase (GST) forms a multigene family of phase II detoxification enzymes which are involved in the detoxification of reactive oxygen species. This study examines whether daily supplementation of kale juice can modulate blood pressure (BP), levels of lipid profiles, and blood glucose, and whether this modulation could be affected by the GSTM1 and GSTT1 polymorphisms. SUBJECTS/METHODS: 84 subclinical hypertensive patients showing systolic BP over 130 mmHg or diastolic BP over 85 mmHg received 300 ml/day of kale juice for 6 weeks, and blood samples were collected on 0-week and 6-week in order to evaluate plasma lipid profiles (total cholesterol, triglyceride, HDL-cholesterol, and LDL-cholesterol) and blood glucose. RESULTS: Systolic and diastolic blood pressure was significantly decreased in all patients regardless of their GSTM1 or GSTT1 polymorphisms after kale juice supplementation. Blood glucose level was decreased only in the GSTM1-present genotype, and plasma lipid profiles showed no difference in both the GSTM1-null and GSTM1-present genotypes. In the case of GSTT1, on the other hand, plasma HDL-C was increased and LDL-C was decreased only in the GSTT1-present type, while blood glucose was decreased only in the GSTT1-null genotype. CONCLUSIONS: These findings suggest that the supplementation of kale juice affected blood pressure, lipid profiles, and blood glucose in subclinical hypertensive patients depending on their GST genetic polymorphisms, and the improvement of lipid profiles was mainly greater in the GSTT1-present genotype and the decrease of blood glucose was greater in the GSTM1-present or GSTT1-null genotypes.

• Natural Product Sciences
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• v.3 no.2
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• pp.81-88
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• 1997

NAD(P)H:quinone reductase (QR) is one of the protective phase II enzymes against toxicity that accomplishes the capacity of detoxification by modulating the effects of mutagens and carcinogens. The detoxification mechanism is that quinone reductase promotes the 2-electron reduction of quinones to hydroquinones which are less reactive. This study is to search new inducers of quinone reductase from natural products, which can be used as cancer chemopreventive agents. Plant extracts were evaluated by using quinone reductase generating system With Hepa 1c1c7 murine hepatoma cell lines for enzyme inducing properties and crystal violet staining method for the measurement of cytotoxicity provoked. We have tested approximately 106 kinds of natural products after partition into n-hexane, ethyl acetate and aqueous layers from 100% methanol extracts of natural products. The ethyl acetate fractions of Vitex rotundifolia $(fruits,\;2FC:\;12.7\;{\mu}g/ml)$, Cnidium officinale $(aerial\;parts,\;2FC:\;10.5\;{\mu}g/ml)$, Chrysanthemum sinese $(flowers,\;2FC:\;17.4{\mu}g/ml)$ and the hexane fractions of Angelica gigas $(roots,\;2FC:\;13.2\;{\mu}g/ml)$, Smilax china $(roots,\;2FC:\;l1.9\;{\mu}g/ml)$, Sophora flavescens $(roots,\;2FC:\;16.3\;{\mu}g/ml)$ revealed the significant induction of quinone reductase in a murine hepatic Hepa 1c1c7 cell culture system.

• Analytical Science and Technology
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• v.23 no.2
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• pp.172-178
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• 2010

Glutathione S-transferase is known to play a crucial role in detoxification in many cases. To develop a herbicide detection biosensor, we in this study attempted to immobilize glutathione S-transferase enzyme on solid supports, polystyrene and agarose, and Na-alginate. These matrixes were attractive materials for the construction of biosensors and might also have utility for the production of immobilized enzyme bioreactors. We also compared the activities of glutathione-S-transferase immobilized OsGSTF3 and free OsGSTF3. The specific activity of the free enzyme in solution was 3.3 higher than the immobilized enzyme. These results suggest that 50% of the enzyme was bound with the catalytic site in polystyrene-alkylamine bead and immobilized enzymes showed 80% remaining activity until 3 times reuse.

• Nutrition Research and Practice
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• v.12 no.2
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• pp.118-128
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• 2018

BACKGROUND/OBJECTIVES: Glutathione s-transferase (GST) is involved in the formation of a multigene family comprising phase II detoxification enzymes, involved in the detoxification of reactive oxygen species. This study evaluated whether daily supplementation with kale juice could modulate levels of plasma antioxidant vitamins and oxidative stress-related parameters. We further examined whether this modulation was affected by combined GSTM1 and T1 polymorphisms. SUBJECTS/METHODS: Totally, 84 subclinical hypertensive patients having systolic blood pressure (BP) over 130 mmHg or diastolic BP over 85 mmHg, received 300 mL of kale juice daily for 6 weeks. Blood samples were drawn before start of study and after completion of 6 weeks. RESULTS: After supplementation, we observed significant decrease in DNA damage and increase in erythrocyte catalase activity in all genotypes. Plasma level of vitamin C was significantly increased in the wild/null and double null genotypes. The plasma levels of ${\beta}-carotene$, erythrocyte glutathione peroxidase activity, and nitric oxide were increased only in the wild/null genotype after kale juice supplementation. CONCLUSIONS: The effect of kale juice was significantly greater in the GSTM1 null genotype and wild/null genotype groups, suggesting possibility of personalized nutritional prescriptions based on personal genetics.

• Korean journal of applied entomology
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• v.61 no.1
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• pp.155-163
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• 2022

The application of fungicides is indispensable to global food security, and their use has increased in recent times. Fungicides, directly or indirectly, have impacted insects, leading to genetic and molecular-level changes. Various detoxification mechanisms allow insects to eliminate reactive oxygen species (ROS) toxicity induced by agrochemicals including fungicides. In the present study, we analyzed the mRNA expression levels of detoxifying enzymes in Tenebrio molitor larvae following exposure to non-lethal doses (0.2, 2, and 20 ㎍/µL) of a fungicide captan. Transcripts of peroxidases (POXs), catalases (CATs), superoxide dismutases (SODs), and glutathione-s-transferases (GSTs) were screened from the T. molitor transcriptome database. RT-qPCR analysis showed that TmPOX5 mRNA increased significantly 24 h post-captan exposure. A similar increase was noticed for TmSOD4 mRNA 3 h post-captan exposure. Moreover, the expression of TmCAT2 mRNA increased significantly 24 h post-treatment with 2 ㎍/µL captan. TmGST1 and TmGST3 mRNA expression also increased noticeably after captan exposure. Taken together, these results suggest that TmPOX5 and TmSOD4 mRNA can be used as biomarkers or xenobiotics sensors for captan exposure in T. molitor, while other detoxifying enzymes showed differential expression.

• Journal of Life Science
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• v.11 no.5
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• pp.405-414
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• 2001

Protaetia brevitarsis has been utilized as an ingredient of the description for the treatment of patients with chronic hepatic diseases in oriental medicine. This study was attempted to investigate whether Protaetia brevitarsis extract(PBE) protects or modulates the liver injuries induced by carbon tetrachloride or ethanol in Sprageue-Dawley rate. The liver injuries of rats induced by the treatment of carbon tetrachloride or ethanol were manifested by the observation of the significant changes in liver weight, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, serum thiobarbituric acid reactive substances (TBARS), and microsomal detocification enzymes(cytochrome P_450), cytochrome b$_{5}$, and cytochrome b$_{5}$ reductase).The effect of PBF on the liver damage induced by the chemicals was evaluated with the extent modulated in change of biochemical parameters above. Exposure to ethanol alone resulted a significant change in the ration of liver per body weight, ALT activity, and microsomal detoxification enzymes (cytochrome P_450, cytochrome b$_{5}$, and cytochrome b$_{5}$ reductase), but did not significantly changes in the levels of serum AST activity and TBARS. Pretreatment coith PBE did not modulate the alteration of the ratio of liver to body weigth, and the activities of serum aminotransferascs (AST. ALT), TBARS, and micro somal detoxification enzyme (cytochrome p_450, cytochrome b$_{5}$,and cytochrome b$_{5}$ reductase. These result suggested that PBE has not appreciable therapeutic effect on carbon tetrachloride or ethanol induced hepatotoxicity.

• Korean journal of applied entomology
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• v.61 no.1
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• pp.143-154
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• 2022

Plant secondary metabolites play an important role in insect-plant interactions. Herbivorous insects have various strategies to cope with the plant defensive compounds. Polyphagous insects feed on a wide variety of plant species, and their detoxification mechanisms are more complex since they tend to respond to a large array of different plant-derived chemicals. Alternatively, oligophagous insects specialize on only a few related plant species and may be expected to have a more efficient form of adaptation. This adaptation could involve either the production of large quantities of enzymes to detoxify their defensive compounds or the sequestration of the compounds or their metabolites. The oriental tobacco budworm, Helicoverpa assulta, is a specialist herbivore, feeding on a few plants of Solanaceae, such as tobacco and hot pepper. Understanding its host-plant adaptation not provides an important insight on physiology, ecology and evolution of specialist herbivores, but also gives a clue to develop management strategies of the pest species such as H. assulta. This paper briefly reviews the specialist, H. assulta, focusing on its host range, larval associations with the host plants, and detoxification mechanisms to nicotine and capsaicin, two characteristic defensive compounds derived from its two major host plants, tobacco and hot pepper, respectively. It summarizes the relevant research over the last half century and provides a future perspective on this subject.