• Food Science and Preservation
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• v.19 no.3
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• pp.443-450
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• 2012

Recently, NADPH oxidase 4 (NOX4)-mediated generation of intracellular reactive oxygen species (ROS) was proposed to accelerate adipogenesis of 3T3-L1 cell. We have previously shown that Cheonnyuncho (Opuntia humifusa) extract significantly inhibited adipocyte differentiation via downregulation of $PPAR{\gamma}$ (peroxisome proliferator-activated receptor gamma) gene expression. In this study, we focused on the molecular mechanism(s) of NOX4, G6PDH (glucose-6-phosphate dehydrogenase) and antioxidant enzymes in anti-oxidative activities of 3T3-L1 adipocytes. Our results indicate that Cheonnyuncho extracts markedly inhibits ROS production during adipogenesis in 3T3-L1 cells. Cheonnyuncho extracts suppressed the mRNA expression of the pro-oxidant enzyme such as NOX4 and the NADPH-producing G6PDH enzyme. In addition, treatment with Cheonnyuncho extract was found to upregulate mRNA levels of antioxidant enzymes such as Mn-SOD (manganese-superoxide dismutase), Cu/Zn-SOD (copper/zinc-SOD), glutathione peroxidase (GPx), glutathion reductase (GR), and catalase, all of which are important for endogenous antioxidant responses. These data suggest that Cheonnyuncho extract may be effective in preventing the rise of oxidative stress during adipocyte differentiation through mechanism(s) that involves direct down regulation of NOX4 and G6PDH gene expression or via upregulation of endogenous antioxidant responses.

• Korean Journal of Poultry Science
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• v.49 no.4
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• pp.211-220
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• 2022

Poultry are exposed to extremely high levels of oxidative stress as a consequence of the excessive production of reactive oxygen species (ROS) induced by endogenous and exogenous stressors, such as high-stocking densities, thermal stress, environmental and feed contamination, along with factors associated with intensive breeding systems. Oxidative stress promotes lipid peroxidation, DNA damage, and inflammation, which can have detrimental effects on the health of birds. During the course of evolution, birds have developed antioxidant defense mechanisms that contribute to maintaining homeostasis when exposed to endogenous and exogenous stressors. The primary antioxidant defense systems are enzymatic and non-enzymatic in nature and play roles in protecting cells from ROS attack. Recently, plant flavonoids, which have been established to reduce oxidative stress, have been attracting considerable attention as potential feed additives. Flavonoids are a group of polyphenolic compounds that can be stabilized by binding structural compounds with ROS, and can promote the elimination of ROS by inducing the expression of antioxidant enzymes. However, although flavonoids can contribute to reducing lipid peroxidation and thereby enhance the antioxidant capacity of birds, they have low solubility in the gastrointestinal tract, and consequently, it is necessary to develop a delivery technology that can facilitate the effect intestinal absorption of these compounds. Furthermore, it is important to determine the dietary levels of flavonoids by assessing the exact antioxidant effects in the gastrointestinal tract wherein the concentrations of dietary flavonoids are highest. It is also necessary to examine the expression of transcriptional factors and vitagenes associated with the efficient antioxidant effects induced by flavonoids. It is anticipated that the application of flavonoids as natural antioxidants will become a particularly important field in the poultry industry.

• The Korean Journal of Malacology
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• v.30 no.4
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• pp.399-408
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• 2014

Glutathione S-transferases (GSTs) are a superfamily of detoxification enzymes that primarily catalyze the nucleophilic addition of reduced glutathione to both endogenous and exogenous electrophiles. In this study, we isolated and characterized a full-length of alpha class GST cDNA from the abalone (Haliotis discus hannai). The abalone GST cDNA encodes a 223-amino acid polypeptide with a calculated molecular mass of 25.8 kDa and isoelectric point of 5.69. Multiple alignments and phylogenetic analysis with the deduced abalone GST protein revealed that it belongs to the alpha class GSTs and showed strong homology with disk abalone (Haliotis discus discus) putative alpha class GST. Abalone GST mRNA was ubiquitously detected in all tested tissues. GST mRNA expression was comparatively high in the mantle, gill, liver, and digestive duct, however, lowest in the hemocytes. Expression level of abalone GST mRNA in the mantle, gill, liver, and digestive duct was 182.7-fold, 114.8-fold, 4675.8-fold, 406.1-fold higher than in the hemocytes, respectively. Expression level of abalone GST mRNA in the liver was peaked at 6 h post-infection with Vibrio parahemolyticus and decreased at 12 h post-infection. While the expression level of abalone GST mRNA in the hemocytes was drastically increased at 3 h post-infection with Vibrio parahemolyticus. These results suggest that abalone GST is conserved through evolution and may play roles similar to its mammalian counterparts.

• Journal of Life Science
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• v.16 no.3 s.76
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• pp.409-414
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• 2006

Molecular chaperones and folding enzymes in the endoplasmic reticulum (ER) associate with the newly synthesized proteins to prevent their aggregation and help them fold and assemble correctly. Chaperone function of BiP, which is a Hsp70 homologue in ER, is controlled by the N-terminal ATPase domain. The ATPase activity of the ATPase domain is affected by regulatory factors. BAP was identified as a nucleotide exchange factor of BiP (Grp78), which exchanges ADP with ATP in the ATPase domain of BiP This study presents whether BAP can influence folding of a protein, immunoglobulin heavy chain that is bound to BiP tightly. We first examined which nucleotide of ADP and ATP affects on BAP binding to BiP The data showed that endogenous BAP of HEK293 cells prefers ADP for binding to BiP in vitro, suggesting that BAP first releases ADP from the ATPase domain in order to exchange with ATP. Immunoglobulin heavy chain, an unfolded protein substrate, was released from BiP in the presence of BAP but not in the presence of ERdj3, which is another regulatory factor for BiP accelerating the rate of ATP hydrolysis of BiP The ADP-releasing function of BAP was, therefore, believed to be responsible for immunoglobulin heavy chain release from BiP. Grp170, another Hsp70 homologue in ER, did not co-precipited with BAP from $[^{35}S]$-metabolic labeled HEK293 lysate containing both overexpressed Grp170 and BAP. These data suggested that BAP has no specificity to Grp170 although the ATPase domains of Grp170 and BiP are homologous each other.

• Genomics & Informatics
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• v.5 no.4
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• pp.161-167
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• 2007

Glucuronidation by the uridine diphosphateglucuronosy-ltransferase 1A enzymes (UGT1As) is a major pathway for elimination of particular drugs and endogenous substances, such as bilirubin. We examined the relation of eight single nucleotide polymorphisms (SNPs) and haplotypes of the UGT1A gene with their clinical factors. For association analysis, we genotyped the variants by direct sequencing analysis and polymerase chain reaction (PCR) in 218 healthy Koreans. The frequency of UGT1A1 polymorphisms, -3279T>G, -3156G>A, -53 $(TA)_{6>7}$, 211G>A, and 686C>A, was 0.26, 0.12, 0.08, 0.15, and 0.01, respectively. The frequency of -118 $(T)_{9>10}$ of UGT1A9 was 0.62, which was significantly higher than that in Caucasians (0.39). Neither the -2152C>T nor the -275T>A polymorphism was observed in Koreans or other Asians in comparison with Caucasians. The -3156G>A and -53 $(TA)_{6>7}$ polymorphisms of UGT1A were significantly associated with platelet count and total bilirubin level (p=0.01, p=0.01, respectively). Additionally, total bilirubin level was positively correlated with occurrence of the UGT1A9-118 $(T)_{9>10}$ rare variant. Common haplotypes encompassing six UGT1A polymorphisms were significantly associated with total bilirubin level (p=0.01). Taken together, we suggest that determination of the UGT1A1 and UGT1A9 genotypes is clinically useful for predicting the efficacy and serious toxicities of particular drugs requiring glucuronidation.

• Korean Journal of Agricultural Science
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• v.42 no.4
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• pp.407-414
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• 2015

To increase antioxidative activity of Chungkukjang, the protective effect of Seoritae Chungkukjang (SC) added with green tea powder against oxidative stress was evaluated under the cellular system using LLC-$PK_1$ cells. The treatment of 3-morpholinosydnonimine showed increase in lipid peroxidation, and decrease in endogenous anti-oxidant enzymes activity and cell viability. The methanol extract of SC inhibited lipid peroxidation by 70.9%, and significantly increased cell viability up to more than 33.2%. In addition, it enhanced superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. Particularly, the addition of green tea in SC exerted protective effect against oxidative stress by ONOO- through elevation in activities of SOD and GSH-Px, and inhibition of lipid peroxidation. More addition of green tea showed stronger protective activity. These results suggest that the addition of green tea to SC leads to the increase in the antioxidative effect of Chungkukjang through elevation in antioxidative enzyme activities and protection from lipid peroxidation.

• Journal of environmental and Sanitary engineering
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• v.7 no.2
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• pp.95-110
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• 1992

Much progress has been made in understanding the subcellular events of the human lung injuries after acute exposure to environmental air pollutants. Host of those events represent oxidative damages mediated by reactive oxygen species such as superoxide, hydrogen peroxide, and the hydroxy, free radical. Recently, nitric oxide (NO) was found to be endogenously produced by endothelial cells and cells of the reticulo-endothelial system as endothelialderived relaxation factor (EDRF) which is a vasoactive and neurotransmitter substance. Together with superoxide, NO can form another strong oxidant, peroxonitrite. The relative importance of exogenous sources of $N0/N0_2$ and endogenous production of NO by the EDRF producing enzymes in the oxidative stresses to the heman lung has to be elucidated. The exact events leading to chronic irreversible damage are still yet to be known. From chronic exposure to oxidant gases, progressive epithelial and interstitial damages develop. Type I epithelial cells become thicker and cover a smaller average alveolar surface area while thee II cells proliferate instead. Under acute damages, the extent of loss of the alveolar epithelial cell lining, especially type II cells appears to be a good predictor of the ensuing irreversible damage to alveolar compartment. Interstitial matrix undergo remodeling during chronic exposure with increased collagen fibers and interstitial fibroblasts. However, Inany of these changes can be reversed after cessation of exposure. Among chronic lung injuries, genetic damages and repair responses received particular attention in view of the known increased lung cancer risks from exposure to several air pollutants. Heavy metals from foundry emission, automobile traffics, and total suspended particulate, especially polycystic aromatic hydrocarbons have been positively linked with the development of lung cancer. Asbestos in another air pollutant with known risk of lung cancer and mesothelioma, but asbestos fibers are nonauthentic in most bioassays. Studies using the electron spin resonance spin trapping method show that the presence of iron in asbestos accelerates the production of the hydroxy, radical in vitro. Interactions of these reactive oxygen species with particular cellular components and disruption of cell defense mechanisms still await further studies to elucidate the carcinogenic potential of asbestos fibers of different size and chemical composition. The distribution of inhaled pollutants and the magnitude of their eventual effects on the respiratory tract are determined by pollutant-independent physical factors such as anatomy of the respiratory tract and level and pattern of breathing, as well as by pollutant-specific phyco-chemical factors such as the reactivity, solubility, and diffusivity of the foreign gas in mucus, blood and tissue. Many of these individual factors determining dose can be quantified in vitro. However, mathematical models based on these factors should be validated for its integrity by using data from intact human lungs.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5311-5316
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• 2014

Nuclear factor erythroid 2-related factor 2 (Nrf2) has been recognized as a transcription factor that controls mechanisms of cellular defense response by regulation of three classes of genes, including endogenous antioxidants, phase II detoxifying enzymes and transporters. Previous studies have revealed roles of Nrf2 in resistance to chemotherapeutic agents and high level expression of Nrf2 has been found in many types of cancer. At physiological concentrations, luteolin as a flavonoid compound can inhibit Nrf2 and sensitize cancer cells to chemotherapeutic agents. We reported luteolin loaded in phytosomes as an advanced nanoparticle carrier sensitized MDA-MB 231 cells to doxorubicin. In this study, we prepared nano phytosomes of luteolin to enhance the bioavailability of luteolin and improve passive targeting in breast cancer cells. Our results showed that cotreatment of cells with nano particles containing luteolin and doxorubicin resulted in the highest percentage cell death in MDA-MB 231cells (p<0.05). Furthermore, luteolin-loaded nanoparticles reduced Nrf2 gene expression at the mRNA level in cells to a greater extent than luteolin alone (p<0.05). Similarly, expression of downstream genes for Nrf2 including Ho1 and MDR1 were reduced significantly (p<0.05). Inhibition of Nrf-2 expression caused a marked increase in cancer cell death (p<0.05). Taken together, these results suggest that phytosome technology can improve the efficacy of chemotherapy by overcoming resistance and enhancing permeability of cancer cells to chemical agents and may thus be considered as a potential delivery system to improve therapeutic protocols for cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3335-3340
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• 2016

Background: Oral submucous fibrosis (OSF) is a precancerous condition with a 4 to13% malignant transformation rate. Related to the habit of areca nut chewing it is mainly prevalent in South-east Asian countries where the habit of betel quid chewing is frequently practised. On chewing, alkaloids and polyphenols are released which undergo nitrosation and give rise to N-nitrosamines which are cytotoxic agents. CYP450 is a microsomal enzyme group which metabolizes various endogenous and exogenous chemicals including those released by areca nut chewing. CYP1A1 plays a central role in metabolic activation of these xenobiotics, whereas CYP2E1 metabolizes nitrosamines and tannins. Polymorphisms in genes that code for these enzymes may alter their expression or function and may therefore affect an individuals susceptibility regarding OSF and oral cancer. The present study was therefore undertaken to investigate the association of polymorphisms in CYP1A1 m2 and CYP2E1 (RsaI/PstI) sites with risk of OSF among areca nut chewers in the Northern India population. A total of 95 histopathologically confirmed cases of OSF with history of areca nut chewing not less than 1 year and 80, age and sex matched controls without any clinical signs and symptoms of OSF with areca nut chewing habit not less than 1 year were enrolled. DNA was extracted from peripheral blood samples and polymorphisms were analyzed by PCR-RFLP method. Gene polymorphism of CYP1A1 at NcoI site was observed to be significantly higher (p = 0.016) in cases of OSF when compared to controls. Association of CYP1A1 gene polymorphism at NcoI site and the risk of OSF (Odd's Ratio = 2.275) was also observed to be significant. However, no such association was observed for the CYP2E1 gene polymorphism (Odd's Ratio = 0.815). Our results suggest that the CYP1A1 gene polymorphism at the NcoI site confers an increased risk for OSF.

• Journal of The Korean Society of Grassland and Forage Science
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• v.31 no.1
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• pp.15-24
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• 2011

The glutathione (GSH) concentration in leaves of different maturities and roots of forage rape (Brassica napus L.) supplied with four levels of external $SO_4^{2-}$ (0, 0.1, 1.0 and 2.0 mM) supply were measured. The relationships of GSH concentration with $SO_4^{2-}$ uptake, ATP sulfurylase (ATPS) and O-acteylserine (thiol) lyase (OASTL) activity were also assessed. The $SO_4^{2-}$ uptake increased in parallel with the external $SO_4^{2-}$ supply, while protein concentration was not significantly changed. The ATPS activity increased continuously with decreasing $SO_4^{2-}$ supply from 2.0 to 0 mM, while the OASTL activity decreased significantly only at S-deficient conditions (0 and 0.1 mM). The GSH concentration in the young leaves, middle leaves and roots continuously increased (except for between 1.0 and 2.0 mM in the middle leaves and roots) as the external S supply was increased, but no significant changes occurred in the old leaves. The increased endogenous GSH concentration, affected by the $SO_4^{2-}$ supply level, was significantly related with the decrease in ATPS activity in both leaves and roots, and the decrease in OASTL activity only in leaves..