• Toxicological Research
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• v.13 no.4
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• pp.339-347
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• 1997

Disulfiram (DSF) and diethyldithiocarbamate (DDC), a reduced form of DSF, protect the liver against toxicant-induced injury through inhibition of cytochrome P450 2E1. The effect of DSF and DDC on the levels of major hepatic microsomal epoxide hydrolase (mEH) and glutathione S-transferase (GST) expression was comparatively studied, given the view that these enzymes are involved in terminal detoxification events for high energy intermediates of xenobiotics. Treatment of rats with a single dose of DSF (20-200 mg/kg, po) resulted in 2- to 15-fold increases in the mEH mRNA level at 24 hr with the ED$_{50}$ value being noted as 60 mg/kg. The mEH mRNA level was elevated ~15-fold at 24 hr after treatment at the dose of 100 mg/kg, whereas the hepatic mRNA level was rather decreased from the maximum at the dose of 200 mg/kg, indicating that DSF might cause cytotoxicity at the dose. In contrast to the effect of DSF, DDC only minimally elevated the mEH mRNA level at the doses employed. DSF moderately increased the major GST mRNA levels in the liver as a function of dose, resulting in rGSTA2, rGSTA3/5 or rGSTM1 mRNA levels being elevated 3- to 4-fold at 24 hr post-treatment, whereas the rGSTM2 mRNA level was not altered. DDC, however, failed to stimulate the mRNA levels for major GST subunits, indicating that the reduced form of DSF was ineffective in stimulating the GST the expression. The effect of other organosulfides including aldrithiol, 2, 2'-dithiobis(benzothiazole) (DTB), tetramethylthiouram disulfide (TMTD) and allyl disulfide (ADS) on the hepatic mEH and GST mRNA expression was assessed in rats in order to further confirm the increase in the gene expression by other disulfides. Treatment of rats with aldrithiol (100 mg/kg, po) resulted in a 16-fold increase in the mEH mRNA level at 24 hr post-treatment. DTB, TMTD and ADS also caused 5-, 9- and 12-fold increases in the rnRNA level, respectively, as compared to control. Thus, all of the disulfides examined were active in stimulating the mEH gene in the liver. The organosulfides significantly increased the rGSTA2, rGSTA3, rGSTA5 and rGSTM1 mRNA levels at 24 hr after administration. In particular, aldrithiol was very efficient in stimulating the rGSTA and rGSTM genes among the disulfides examined. These results provide evidence that DSF and other sulfides effectively stimulate the mEH and major GST gene expression at early times in the liver and that DDC, a reduced form of DSF, was ineffective in stimulating the expression of the genes, supporting the conclusion that reduced form(s) of organosulfur compound(s) might be less effective in inducing the mEH and GST genes through the antioxidant responsive element(s).

• Journal of Life Science
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• v.23 no.8
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• pp.978-983
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• 2013

Kinesin-II, a molecular motor, consists of two different motor subunits, KIF3A and KIF3B, and one large kinesin superfamily-associated protein 3 (KAP3), forming a heterotrimeric complex. KAP3 is associated with the tail domains of motor subunits. However, its exact role remains unclear. Here, we demonstrated KAP3 binding to the carboxyl (C)-terminal tail region of HS-associated protein X-1 (HAX-1). HAX-1 bound to the C-terminal region of KAP3, but not to KIFs (KIF3A, KIF3B, and KIF5B) and the kinesin light chain (KLC) in the yeast two-hybrid assays. The interaction was further confirmed in the glutathione S-transferase (GST) pull-down assay and by co-immunoprecipitation. Anti- HAX-1 antibody as well as anti-KIF3A antibody co-immunoprecipitated KIF3B and KAP3 from mouse brain extracts. These results suggest that KAP3 could mediate the interaction between Kinesin-II and HAX-1.

• Korean Journal of Environmental Biology
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• v.26 no.2
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• pp.87-93
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• 2008

To assess effects of contaminants on fish in Nakdong river, feral yellowfin goby Acanthogobius flavimanus were caugt in two different sites and its hepatic monooxygenase enzyme, including cytochrome P450 (CYP), NADPH-cytochrome P450 reductase (P450R), NADH-cytochrome b5 reductase (b5R), ethoxyresorufin deethylase (EROD), glutathione S-transferase (GST) were quantitatively determined. Gonadosomatic index (GSI), hepatosomatic index (HSI) and three sex steroid hormone (17$\beta$-estradiol, E2; testosterone, T; 11-ketotestosterone, 11-KT) levels of the fish were also investigated. HSI of fish from polluted site (site 1) were significantly higher than that of unpolluted site (site 2), but GSI levels were significantly lower in polluted site. No significant differences in plasma 11-KT and T levels were observed in two sites surveyed. E2 level was, however, significantly (p<0.05) higher in female fish from site 1 than site 2. In addition, hepatic EROD activity and CYP level of site 1 fish were lower than those of site 2 fish, whereas relatively high levels of P450R, b5R and GST activities were found in site 1. The results imply that yellowfin goby, especially female fish in Nakdong river estuary are affected from contaminants disrupting sex steroid hormone system.

• Applied Microscopy
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• v.31 no.1
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• pp.9-18
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• 2001

This study was designed to determine the effects of Protaetia Orientalis larva (Gory et Perchlon) on the in vivo lipid metabolism in Sprague Dawley rats with the administration of carbon tetrachloride to induce damage in the liver. At the end of 8th week, serum levels of GOP and GPT, hepatic cholesterol levels, HDL-cholesterol, triglycerides and phospholipids were determined. In addition, activities of antioxidative enzymes were also determined. The administration of carbon tetrachloride resulted in increase of serum GOT and GPT, liver triglyceride and total cholesterol. On the other hand, those fed in combination with carbon tetrachloride and Protaetia Orientalis larva decreased those lipid parameters . Carbon tetrachloride feeding resulted in decrease of liver phospholipid, whereas that of the rat fed in combination with carbon tetrachloride and Protaetia Orientalis larva was increased. In antioxidative defense system, carbon tetrachloride led to a significant decrease in activities of catalase, total SOD, Cu, Zn-SOD and glutathione-S-transferase. However, those activities of the rat fed in combination with carbon tetrachloride and Protaetia Orientalis larva was significantly increased. Hepatocytes of carbon tetrachloride administered rats showed increased lipid droplets and micro-filaments. However, those of the rat fed in combination with carbon tetrachloride and Protaetia Orientalis larva were reduced in the number and the size.

• Proceedings of the Ginseng society Conference
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• 1984.09a
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• pp.21-26
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• 1984

The balance between metabolic activation of xenobiotics and detoxification of their active metabolites may playa vital role in controlling mutagenic and carcinogenic processes. To assess the possible role of P. ginseng C.A. Meyer in detoxification of xenobiotics, we studied the effects of ginseng on several parameters of the monooxygenasd system, including benzo(a) pyrene monooxygenase(AHH) and benzo(a) pyrene epoxide hydratase(EH) as well as effects of ginseng on the conjugation system. Test animals receiving ginseng saponin-fraction induced epoxide hydratase activity to over $150\%$ (20mg/kg b.w.) of the control and increased glutathione transferase activity (GSH-T) up to $140\%$ (20mg/kg b.w.) of the control, whereas no significant changes were observed in the benzopyrene monooxygenase activity (AHH). Such a selective induction of the inactivation enzyme epoxide hydratase, combined with a marked elevation of the detoxifying enzyme glutathione transferase, without a concurrent induction of benzopyrene monooxygenase which is responsible for the formation of carcinogenic intermediates, demonstrates that ginseng has the potential to alter the metabolic course of carcinogenic polycyclic aromatic hydrocarbons, and thereby enhance detoxification. Thus, ginseng may play an important role in the prevention of tumors caused by carcinogens.

• Journal of Korean Society on Water Environment
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• v.32 no.5
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• pp.419-432
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• 2016

The aim of this study is to assess the influence of effluent discharge from a sewage treatment plant by evaluating oxidative stress and histopathological alterations in freshwater crucian carp Carassius auratus collected from the Eungcheon stream, located in Korea. Catalase activity in the gills, liver, and kidneys of C. auratus was collected from mixing zones; the downstream site was notably higher of fish than that of the upstream site. In addition, the activity of glutathione-S-transferase in the gills and liver was significantly higher in samples from the mixing zone than in those from the upstream site (p < 0.05). In addition, significantly elevated lipid peroxidation levels were observed in fish livers sampled from the mixing zone than in those from the upstream site (p < 0.05). Significant histopathological alternations were also observed in C. auratus, with the order of magnitude changes being liver > kidney > gills. These findings suggest that the liver is most affected by effluent discharge. The degree of tissue changes (DTC) indicate that the highest level occurred in samples from the mixing zone (30.98 ± 5.40) followed by those from the downstream site (19.28 ± 4.31) and was the lowest in samples from the upstream site (4.83 ± 2.67). These findings indicate that fish collected from the mixing zone are most affected by effluent discharge and both oxidative stress and histopathological indices are useful tools for monitoring contaminated rivers and streams.

• Journal of Life Science
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• v.19 no.8
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• pp.1055-1061
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• 2009

${\alpha}$-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors are widespread throughout the central nervous system and appear to serve as synaptic receptors for fast excitatory synaptic transmission mediated by glutamate. Their modulation is believed to affect learning and memory. To identify the interaction proteins for the AMPA receptor subunit glutamate receptor-interacting protein 1 (GRIPl), GRIP1 interactions with armadillo family protein p0071/plakophilin-4 were investigated. GRIP1 protein bound to the tail region of p0071/plakophilin-4 but not to other armadillo family protein members in a yeast two-hybrid assay. The "S-X-V" motif at the carboxyl (C)-terminal end of p0071/plakophilin-4 is essential for interaction with GRIP1. p0071/plakophilin-4 interacted with the Postsynaptic density-95/Discs large/Zona occludens-1 (PDZ) domains of GRIPI in the yeast two-hybrid assay, as is indicated also by Glutathione S-transferase (GST) pull-down, and co-immunoprecipitated with GRIP1 antibody in brain fraction. The findings of this study provide evidence that p0071/plakophilin-4 is an interactor of GRIP1.

• Journal of Life Science
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• v.23 no.4
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• pp.586-594
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• 2013

Post-translational O-GlcNAc modification (O-GlcNAcylation) of serine or threonine is a new protein modulation mechanism. In contrast to the classical glycosylation, O-GlcNAcylation occurs in a one-step transfer of O-GlcNAc on both nuclear and cytoplasmic proteins. In contrast to the general consensus that O-GlcNAc is a final modification, a recent paper (J Proteome Res. 2011 10:2725-2733) showed the presence of O-GlcNAc-P on a synaptic assembly protein AP180. This finding raises a fundamental question about its prevalence. To address this question, we used proteomics to identify those proteins that were phospho-signal enriched by GlcNAc kinase (NAGK). Comparison of pDsRed2-$NAGK_{WT}$-transfected HEK293T cell extract with pDsRed2-$NAGK_{D107A}$-transfected control culture revealed 15 phospho-signal increased spots. Excluding those spots that had no detectable amount of protein expression yielded 7 spots, which were selected for ID determination. Among these, two duplicate spots (two $HSP90{\beta}$ and two ENO1 spots) were shown to be O-GlcNAcylated, two (dUTP nucleotidohydrolase mitochondrial isoform 2, glutathione S-transferase P) were not known to be involved in O-GlcNAcylation, and one (heat shock protein gp96 precursor or grp94) was a glycoprotein. The increase in the phospho-levels of O-GlcNAc by NAGK strongly indicates that these proteins are phosphorylated on O-GlcNAc. Our present data support the idea that O-GlcNAc is not a terminal modification.

• Korean Journal of Medicinal Crop Science
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• v.10 no.1
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• pp.29-36
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• 2002

Epimedium koreanum Nakai(EKN) has traditionally been well-known as a herbal medicine for the promotion of stamina and the improving sexual activity of human in oriental countries including Korea and China. The aim of this study was to investigate the effect of dietary supplementation of EKN water-extract(0.025%,w/v) on age-related change of xenobiotic metabolizing system in rat liver. Long-term supply of the EKN extract to rats did not induce any discernible signs. However, the mass of liver and kidney were slightly increased by the dietary supplementation. Level of cytochrome P450, NADPH cytochrome P450 reductase, P450 dependent ethoxycoumarin O-deethylase benzphetamine N-demethylase and glutathione-S-transferase in liver were decreased with age, but, these activities in 24 months of age were declined more in rats supplied with EKN extract. Level of cytochrome b5 and NADH-cytochrome b5 reductase were also decreased with age, however, there was no significant difference between with and without EKN extract. These results indicate that long-term supplementation of EKN extract to rats from weaning to 24 months may be a burden on the liver function in old age, and may aggregate the decline of xenobiotic metabolizing enzymes activities in old age.

• Microbiology and Biotechnology Letters
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• v.26 no.4
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• pp.331-337
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• 1998

The biological activities of both ethanol and water extracts from the fruiting body of E. applanata and E. applanata mycelium and the three fractions of ethanol extracts from E. applanata were compared. 91% of MCF7 cell growth was inhibited by adding 0.5 g/l of water extracts of E. applanata and 81% of MCF7 cell growth was inhibited by adding 0.5 g/l of diethyl ether and chloroform fractions. It was also showed that above 60% of Hep3B cell growth was inhibited by adding all samples including the fractions. The ethanol extracts of E. applanata mycelium showed 33.3% of cytotoxicity on normal liver cell, WRL68 in adding 0.5 g/l of the samples and 40% in adding 0.5 g/l of chloroform fractions. The result of anti-mutagenicity of all extracts and fractions including ethanol extracts of Phelinus linteus were showed that diethyl ether fractions were most effective than any other samples. Hypoglycemic activities of diethyl ether and chloroform fractions were the most effective which scores were above 75%. The enhancement of glutathione-S-transferase activity was increased above 2.3 times by adding 1.0 g/l ethanol extracts of E. applanata and diethyl ether, chloroform fractions. It can be concluded that both biological activities of the fruiting body and mycelium of E. applanata were almost equivalent.