• KOREAN JOURNAL OF CROP SCIENCE
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• v.67 no.1
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• pp.41-52
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• 2022

As a cultivar of Korean wheat, 'Keumgang' wheat variety has a fast growth period and can be grown stably. Hexaploid wheat (Triticum aestivum) has moderately high salt tolerance compared to tetraploid wheat (Triticum turgidum L.). However, the molecular mechanisms related to salt tolerance of hexaploid wheat have not been elucidated yet. In this study, the candidate genes related to salt tolerance were identified by investigating the genes that are differently expressed in Keumgang variety and examining salt tolerant mutation '2020-s1340.'. A total of 85,771,537 reads were obtained after quality filtering using NextSeq 500 Illumina sequencing technology. A total of 23,634,438 reads were aligned with the NCBI Campala Lr22a pseudomolecule v5 reference genome (Triticum aestivum). A total of 282 differentially expressed genes (DEGs) were identified in the two Triticum aestivum materials. These DEGs have functions, including salt tolerance related traits such as 'wall-associated receptor kinase-like 8', 'cytochrome P450', '6-phosphofructokinase 2'. In addition, the identified DEGs were classified into three categories, including biological process, molecular function, cellular component using gene ontology analysis. These DEGs were enriched significantly for terms such as the 'copper ion transport', 'oxidation-reduction process', 'alternative oxidase activity'. These results, which were obtained using RNA-seq analysis, will improve our understanding of salt tolerance of wheat. Moreover, this study will be a useful resource for breeding wheat varieties with improved salt tolerance using molecular breeding technology.

• Proceedings of the Korean Society of Plant Biotechnology Conference
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• 2002.04a
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• pp.69-75
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• 2002

Sterols play two major roles in plants: a bulk component in biological membranes and precursors of plant steroid hormones. Physiological effects of plant steroids, brassinosteroids (BRs), include cell elongation, cell division, stress tolerance, and senescence acceleration. Arabidopsis mutants that carry genetic defects in BR biosynthesis or its signaling display characteristic phenotypes, such as short robust inflorescences, dark-green round leaves, and sterility. Currently there are more than 100 dwarf mutants representing 7 genetic loci in Arabidopsis. Mutants of 6 loci, dwf1/dim1/cbb1, cpd/dwf3, dwf4, dwf5, det2/dwf6, dwf7 are rescued by exogenous application of BRs, whereas bri1/dwf2 shares phenotypes with the above 6 loci but are resistant to BRs. These suggest that the 6 loci are defective in BR biosynthesis, and the one locus is in BR signaling. Biochemical analyses, such as intermediate feeding tests, examining the levels of endogenous BR, and molecular cloning of the genes revealed that dwf7, dwf5, and dwf1 are defective in the three consecutive steps of sterol biosynthesis, from episterol to campesterol via 5-dehydroepisterol. Similarly, det2/dwf6, dwf4, and cpd/dwf3 were shown to be blocked in $D^4$ reduction, 22a-hydroxylation, and 23 a-hydroxylation, respectively. A signaling mutant bri1/dwf2 carries mutations in a Leucine-rich repeat receptor kinase. Interestingly, the bri1 mutant was shown to accumulate significant amount of BRs, suggesting that signaling and biosynthesis are dynamically coupled in Arabidopsis. Thus It is likely that transgenic plants over-expressing the rate-limiting step enzyme DWF4 as well as blocking its use by BRI1 could dramatically increase the biosynthetic yield of BRs. When applied industrially, BRs will boost new sector of plant biotechnology because of its potential use as a precursor of human steroid hormones, a novel lead compound for cholesterol-lowering effects, and a various application in plant protection.

• Proceedings of the Korean Society of Plant Biotechnology Conference
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• 2002.04b
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• pp.69-75
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• 2002

Sterols play two major roles in plants: a bulk component in biological membranes and precursors of plant steroid hormones. Physiological effects of plant steroids, brassinosteroids (BRs), include cell elongation, cell division, stress tolerance, and senescence acceleration. Arabidopsis mutants that carry genetic defects in BR biosynthesis or its signaling display characteristic phenotypes, such as short robust inflorescences, dark-green round leaves, and sterility. Currently there are more than 100 dwarf mutants representing 7 genetic loci in Arabidopsis. Mutants of 6 loci, dwf1/dim1/cbb1, cpd/dwf3, dwf4, dwf5, det2/dwf6, dwf7 are rescued by exogenous application of BRs, whereas bri1/dwf2 shares phenotypes with the above 6 loci but are resistant to BRs. These suggest that the 6 loci are defective in BR biosynthesis, and the one locus is in BR signaling. Biochemical analyses, such as intermediate feeding tests, examining the levels of endogenous BR, and molecular cloning of the genes revealed that dwf7, dwf5, and dwf1 are defective in the three consecutive steps of sterol biosynthesis, from episterol to campesterol via 5-dehydroepisterol. Similarly, det2/dwf6, dwf4, and cpd/dwf3 were Shown to be blocked in $D^4$ reduction, 22a-hydroxylation, and 23 a-hydroxylation, respectively. A signaling mutant bri1/dwf2 carries mutations in a Leucine-rich repeat receptor kinase. Interestingly, the bri1 mutant was shown to accumulate significant amount of BRs, suggesting that signaling and biosynthesis are dynamically coupled in Arabidopsis. Thus it is likely that transgenic plants over-expressing the rate-limiting step enzyme DWF4 as well as blocking its use by BRI1 could dramatically increase the biosynthetic yield of BRs. When applied industrially, BRs will boost new sector of plant biotechnology because of its potential use as a precursor of human steroid hormones, a novel lead compound for cholesterol-lowering effects, and a various application in plant protection.

• Journal of Plant Biotechnology
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• v.29 no.2
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• pp.139-144
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• 2002

Sterols play two major roles in plants: a bulk component in biological membranes and precursors of plant steroid hormones. Physiological effects of plant steroids, brassinosteroids (BRs), include cell elongation, cell division, stress tolerance, and senescence acceleration. Arabidopsis mutants that carry genetic defects in BR biosynthesis or its signaling display characteristic phenotypes, such as short robust inflorescences, dark-green round leaves, and sterility. Currently there are more than 100 dwarf mutants representing 7 genetic loci in Arabidopsis. Mutants of 6 loci, dwf1/dim1/cbb1, cpd/dwf3, dwf4, dwf5, det2/dwf6, dwf7 are rescued by exogenous application of BRs, whereas bri1/dwf2 shares phenotypes with the above 6 loci but are resistant to BRs. These suggest that the 6 loci are defective in BR biosynthesis, and the one locus is in BR signaling. Biochemical analyses, such as intermediate feeding tests, examining the levels of endogenous BR, and molecular cloning of the genes revealed that dwf7, dwf5, and dwf1 are defective in the three consecutive steps of sterol biosynthesis, from episterol to campesterol via 5-dehydroepisterol. Similarly, det2/dwf6, dwf4, and cpd /dwf3 were shown to be blocked in D$^4$reduction, 22a-hydroxylation, and 23 a-hydroxylation, respectively. A signaling mutant bril/dwf2 carries mutations in a Leucine-rich repeat receptor kinase. Interestingly, the bri1 mutant was shown to accumulate significant amount of BRs, suggesting that signaling and biosynthesis are dynamically coupled in Arabidopsis. Thus it is likely that transgenic plants over-expressing the rate-limiting step enzyme DWF4 as well as blocking its use by BRIl could dramatically increase the biosynthetic yield of BRs. When applied industrially, BRs will boost new sector of plant biotechnology because of its potential use as a precursor of human steroid hormones, a novel lead compound for cholesterol-lowering effects, and a various application in plant protection.

• 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 Ginseng Research
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• v.44 no.4
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• pp.544-551
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• 2020

Background: Previous studies have shown the insecticidal efficacy of ginsenosides. In the present study, we aimed to investigate the metabolic mechanism related to the inhibitory effect of panaxadiol saponins (PDSs) against the Asian corn borer Ostrinia furnacalis (Guenee). Methods: Third instar larvae of O. furnacalis were fed normal diets with different concentrations of PDSs for 4 days. The consumption index, relative growth rate, approximate digestibility, and conversion of ingested and digested food were recorded. A targeted gas chromatographye-mass spectrometry assay was performed to detect the profiles of amino acids, fatty acids, and carbohydrates in larvae of O. furnacalis. In addition, the activity of detoxification-related enzymes was determined. Results and Conclusions: PDSs decreased the consumption index, relative growth rate, approximate digestibility, and conversion of ingested and digested food in the 3rd instar larvae of O. furnacalis in a dose-dependent manner. PDSs decreased 15 free amino acids, 16 free fatty acids, and 5 carbohydrates and increased the levels of palmitoleic acid, palmitic acid, and 9-octadecenoic acid in the 3rd instar larvae. The activity of detoxification-related enzymes, such as acetylcholinesterase, glutathione S-transferase, cytochrome P450, carboxylesterase, trehalase, acid phosphatase, and alkaline phosphatase, was reduced in a dose-dependent manner in the 3rd instar larvae exposed to PDSs. These data confirmed the inhibitory effect of PDSs against growth, food utilization, and detoxification in the 3rd instar larvae of O. furnacalis and the potential for using PDSs as an efficient tool for insect pest management for O. furnacalis larvae.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.2
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• pp.389-396
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• 2002

In the present work, we examined the mechanism of vasorelaxant effect of scopoletin, an active constituent of Artemisia capillaris on rat thoracic descending aortic rings. Scopoletin induced a concentration-dependent relaxation in rat thoracic descending aortic rings pre-contracted with phenylephrine (EC/sub 50/ = 238.94±37.4 μM), while it was less effective in rat thoracic descending aortic rings precontracted with high potassium solution (KCI 30 mM). Vasorelaxation by scopoletin was significantly inhibited after endothelial removal, but recovered at high concentration. Pretreatment of rat thoracic descending aortic rings with N/sup G/-nitro-L-arginine (100 μM), a nitric oxide synthase inhibitor, and atropine (1 μM), a muscarinic receptor antagonist, significantly inhibited scopoletin-induced relaxation of rat thoracic descending aortic rings. Neither indomethacin (3 μM), an inhibitor of cydooxygenase, nor propranolol (1 μM), a β -adrenoceptor antagonist, modified the effect of scopoletin. The combination of N/sup G/ -nitro-L-arginine (100 μ M) and miconazole (10 μ M), an inhibitor of cytochrome P 450, did not modify the effect of scopoletin, when compared with pretreatment with N/sup G/-nitro-L-arginine(100 μM) alone. Vasorelaxant effect of scopoletin was inverted by pretreatment with diltiazem (10 μM), a Ca/sup 2+/-channel blocker, at low concentration, while restored at high concentration. Apamin (K/sub ca/-channel blocker, 1 μM), 4-aminopyridine (4-AP, K/sub v/-channel blocker, 1 mM), and tetrodotoxin (TTX, Na/sup +/-channel blocker 1 μM) potentiated the vasorelaxant effect of scopoledn, but glibendamide (K/sub ATP/-channel blocker, 10 μM), tetraetylammonium(TEA, non-selective K-channel blocker, 10 mM) did not affect the relaxation of scopoletin. Free radical scavengers (TEMPO, catalase, mannitol) did not modify vascular tone. These results suggest that nitric oxide, Ca/sup 2+/ -channels play a role in endothelium-dependent relaxations to scopoletin in rat aortas, that apamin, 4-AP, TTX but not glibenclamide, TEA potentiated relaxation to scopoletin mediated by these channels, and that free radicals do not concern to the vasorelaxant effect of scopoletin.

• The Korean Journal of Pharmacology
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• v.18 no.1
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• pp.55-63
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• 1982

Lipid peroxidation is the reaction of oxidative deterioration of polyunsaturated lipids and this peroxidation involves the direct reaction of oxygen and lipid to form free radical intermediates, which can lead to autocatalysis. As results of the extensive studies on the lipid peroxidation by many authors, the relationship between lipid peroxidation and the drug metabolizing system as well as the actions of free radicals on the peroxidation was reasonably well known. For a long time, the mechanism of hepatotoxicity of $CCl_4$ was not clearly understood. However, it is now quite well established that $CCl_4$ is activated in vivo to a free radical which is a highly reactive molecule. Therefore, lipid peroxidation which induces the reduction of cytochrome P-450 and aminopyrine demethylase activity is known as decisive event of $CCl_4$ hepatotoxicity. On the other hand, it was also reported that singlet molecular oxygen produces lipid peroxidation in liver microsomes. In this study the effects of benzoyl peroxide on the lipid peroxidation and drug-metabolizing enzyme were examined. Benzoyl peroxide mixed with starch and phosphates etc. is usually used as a food additive for flour bleaching and maturing purpose because of its oxidative property. Albino rats were used for the experimental animals. Benzoyl peroxide was suspended in soybean oil and sesame oil and administered intraperitoneally or orally. TBA value and aminopyrine demethylase activity were determined in liver microsomal fraction and serum. The results were summerized as following. 1) Body weights of animals administered benzoyl peroxide suspension were decreased while that of oil administered group were increased. 2) The activity of aminopyrine demethylase was generally decreased in animals administered oil suspension of benzoyl peroxide. Furthermore, the marked reduction of the enzyme activity was observed in animals administered benzoyl peroxide intraperitoneally. 3) Generally, microsomal TBA values as well as serum TBA were significantly elevated in benzoyl peroxide group in comparison with the control group. However, the more remarkable increase of serum TBA than microsomal TBA was observed in animals administered orally for 6 days. 4) Specifically, the changing pattern of TBA value was notable in serum rather than in liver microsome by intraperitoneal administration of benzoyl peroxide.

• Korean Journal of Clinical Pharmacy
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• v.30 no.1
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• pp.31-35
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• 2020

Objective: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are frequently prescribed medications worldwide for the treatment of hypercholesterolemia. Statins are considered to be well tolerated; however, they have a potential for myotoxicity. Concomitant drugs that inhibit cytochrome P450 3A4 can increase the concentration of statins and thus the risk of developing myotoxicity. The purpose of this study was to evaluate risk factors associated with potential drug-drug interactions in patients receiving statins. Methods: The subjects of this study were patients aged more than 18 years who received at least one prescription of statins in a general hospital located in Chuncheon-si, Korea, between January 1, 2018, and March 31, 2018. Data regarding statin use and baseline characteristics was collected from the computerized hospital database. Logistic regression analysis was used to identify risk factors associated with potential drug-drug interactions. Results: A total of 1061 patients were finally included in the study. The incidence of potential drug-drug interactions was 45% in all subjects. According to the results of the multivariate logistic regression analysis, myocardial infarction as the indication of statin, arrhythmia or heart failure as a comorbidity, and aspartate aminotransferase levels higher than 40 IU/L were significant risk factors for potential drug-drug interactions in study subjects. Diltiazem was the most commonly co-prescribed drug that caused potential drug-drug interactions with statins. Conclusion: There was a considerable rate of potential drug-drug interactions in patients receiving statins. Health care professionals should attempt to reduce potential drug-drug interactions during statin administration.

• Journal of Food Hygiene and Safety
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• v.26 no.3
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• pp.235-241
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• 2011

Although the vegetable Angelica keiskei (AK) has widely been utilized for the purpose of general health improvement among Korean population, its functionalities are not very well defined. In this study, we examined the effects of methanol extract of AK in rats on the biochemical changes induced by two hepatotoxins, D-galactosamine (GalN) and carbon tetrachloride ($CCl_4$). AK was orally administered once daily for 7 days to male rats at 200 and 500 mg/kg, before hepatotoxins. Effects of AK were assessed 24 hr later. AK pretreatments at 200 and 500 mg/kg significantly blunted GalN-induced elevation in liver lipid peroxidation, plasma aspartate-transaminase (AST) and alanine-transaminase (ALT) activities. AK also prevented, after 500 mg/kg but not after 200 mg/kg, the GalN-induced elevation in triglyceride, total cholesterol and LDL-cholesterol levels. Differently from against GalN-induced toxicity, AK did further elevate the $CCl_4$-induced rise in AST, ALT and lipid peroxidation. These results suggest that AK, when pre-administered prior to GalN, exerted protective effects against GalN-induced hepatotoxicity, in contrast however, AK exacerbated that induced by $CCl_4$. To explore possible mechanism for the toxicity-potentiating effects of AK on $CCl_4$, the activity of hepatic drug metabolism after AK treatment was assessed. It was observed that AK increased the activity of aniline hydroxaylase, a cytochrome P450 isoenzyme responsible for metabolic activation of $CCl_4$. This finding suggests that hepatoprotective effects of AK are not equally expected depending on hepatotoxins employed.