• Title/Summary/Keyword: Reductase

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Reductive Depolymerization of Bovine Thyroglobulin Multimers via Enzymatic Reduction of Protein Disulfide and Glutathiony­lated Mixed Disulfide Linkages

  • Liu Xi-Wen;Sok Dai-Eun
    • Archives of Pharmacal Research
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    • v.28 no.9
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    • pp.1065-1072
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    • 2005
  • The nascent thyroglobulin (Tg) multimer molecule, which is generated during the initial fate of Tg in ER, undergoes the rapid reductive depolymerization. In an attempt to determine the depolymerization process, various types of Tg multimers, which were generated from deoxy­cholate-treated/reduced Tg, partially unfolded Tg or partially unfolded/reduced Tg, were subjected to various GSH (reduced glutathione) reducing systems using protein disulfide isomerase (PDI), glutathione reductase (GR), glutaredoxin or thioredoxin reductase. The Tg multimers generated from deoxycholate-treated/reduced Tg were depolymerized readily by the PDI/GSH system, which is consistent with the reductase activity of PDI. The PDI/GSH-induced depolymerization of the Tg multimers, which were generated from either partially unfolded Tg or partially unfolded/reduced Tg, required the simultaneous inclusion of glutathione reductase, which is capable of reducing glutathionylated mixed disulfide (PSSG). This suggests that PSSG was generated during the Tg multimerization stage or its depolymerization stage. In particular, the thioredoxin/thioredoxin reductase system or glutaredoxin system was also effective in depolymerizing the Tg multimers generated from the unfolded Tg. Overall, under the net GSH condition, the depolymerization of Tg multimers might be mediated by PDI, which is assisted by other reductive enzymes, and the mechanism for depolymerizing the Tg multimers differs according to the type of Tg multimer containing different degrees and types of disulfide linkages.

Effects of Sparganii Rhizoma Processed on Rat Lens Aldose Reductase and Anti-oxidant Activities (흑삼릉의 수치에 따른 Aldose Reductase 및 항산화활성에 미치는 영향)

  • 정상훈;신국현;신현경;임순성
    • YAKHAK HOEJI
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    • v.48 no.5
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    • pp.291-296
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    • 2004
  • Sparganium stoloniferum Buch.-Ham. (Sparganiaceae) is a perennial herb which has been used as treatments for menstrual disorder, galactagogue and endometriosis in folk remedies. The Sparganii Rhizoma processed, heated with vinegar, used to different purpose compared with origin in medicine. In order to estimate the different effects between processed (PSR) and unprocessed (USR) Sparganii Rhizoma, extraction and systemic fractionation of the rhizomes were archived. Inhibitory effects of the extracts as well as the fractions of PSR and USR on rat lens aldose reductase and on rat platelet aggregation were investigated for the prevention or the treatment of chronic diabetic complications. Their antioxidant effects, measured using lipid peroxidation of liver tissue and radical scavenging activities on 1,1-diphenyl-picrylhydrazyl in vitro, were evaluated. The most of biological activities tested except rat platelet aggregation, fractions from PSR were shown to exhibit stronger activities than those from USR. It seems that caused by changing of the chemical components by heating process in conditioned with acetic acid. Compounds isolated were shown to significant inhibitory activity on rat lens aldose reductase. Inhibitory activity of compounds isolated on rat lens aldose reductase have been tested in vitro. $IC_{50}$/ (6.31 $\mu$M) of cerebroside I (V) was nearly equal to that (6.32 $\mu$M) of a reference compound, tetrametbylene glutaric acid (TMG).

Polymorphisms of 3-hydroxy-3-methylglutaryl Coenzyme A Reductase Gene Are Not Associated with the Osteonecrosis of Femoral Head in Korean (한국인에서 HMG-CoA reductase 유전자다형성과 대퇴골두무혈성괴사증과의 연관성 분석)

  • Kim, Tae-Ho;Hong, Jung-Min;Lee, Sang-Han;Park, Eui-Kyun;Kim, Shin-Yoon
    • Journal of Life Science
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    • v.18 no.4
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    • pp.427-434
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    • 2008
  • Osteonecrosis of the femoral head (ONFH) is a multifactorial disease and certain individuals are more at risk or may be predisposed to it. An altered lipid metabolism is one of the major risk factors for osteonecrosis, especially corticosteroid therapy and alcoholism. 3-hydroxy-3-methylglutaryl coenzyme A. (HMG-CoA) reductase inhibitors, stalin used as lipid-clearing agent, have been known to decrease the risk of osteonecrosis in patients receiving steroids and affect coagulation and fibrinolysis. Therefore we evaluated the association of HMG-CoA reductase gene polymorphisms and haplotypes between osteonecrosis patients and normal controls. We directly sequenced the HMG-CoA reductase gene in 24 Korean individuals, and identified five sequence variants. Four SNPs (-6933C>T, -6045T>G, +12673G>A, and +18128C>T) were selected and genotyped in 349 male ONFH patients and 300 male control subjects. The genotypes, allele frequencies, and haplotypes of the polymorphisms in the total patients as well as in the subgroup by etiology were not significantly different from those in the control group. In addition, no significant differences between each genotype of the polymorphisms and plasma lipid level could be found in the control group. These results suggest that the polymorphisms and haplotypes of HMG-CoA reductase gene are unlikely to be associated with a susceptibility to ONFH.

The Effects of Scutellaria baicalensis on Experimental Rat Model of Benign Prostatic Hyperplasia (황금(黃芩)이 전립선비대증(前立腺肥大症) Rat에 미치는 영향)

  • Kim, Jing-Sung;Han, Yang-Hee;Kim, Young-Seong
    • The Journal of Internal Korean Medicine
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    • v.30 no.2
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    • pp.327-337
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    • 2009
  • Objective : In benign prostatic hyperplasia, dihydrotestosterone acts as a potent cellular androgen and promotes prostate growth. Inhibiting enzyme 5${\alpha}$-reductase, which is involved in the conversion of testosterone to the active form dihydrotestosterone, reduces excessive prostate growth. Recently Scutellaria baicalensis has been related reports about the effect of baicalein on anti-proliferation of the prostate gland. In this study, we investigated the effects of Scutellaria baicalensis on cytopathological alterations and expression of 5${\alpha}$-reductase in the rat model of benign prostatic hyperplasia induced by castration and testosterone treatment. Methods : Sprague-Dawley rat were treated with testosterone after castration for induction of experimental benign prostatic hyperplasia, which is similar to human benign prostatic hyperplasia in histopathological profiles. Scutellaria baicalensis as an experimental specimen, and finasteride as a positive control, were administered orally. The prostates were evaluated by histopathological changes, testosterone levels, and the expression of 5${\alpha}$-reductase genes. Results : While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation, the rats treated with Scutellaria baicalensis showed a diminished range of tissue damage. In the reverse transcription-polymerase chain reaction(RT-PCR) of 5${\alpha}$-reductase genes. Scutellaria baicalensis inhibited the expression of 5${\alpha}$-reductase genes. Conclusions : These findings suggest that Scutellaria baicalensis may protect glandular epithelial cells and also inhibit stromal proliferation in association with the suppression of 5${\alpha}$-reductase. From theses results, we suggest that Scutellaria baicalensis could be a useful remedy agent for treating benign prostatic hyperplasia.

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Effects of Natural Products on the Induction of NAD(P)H: Quinone Reductase in Hepa 1c1c7 Cells for the Development of Cancer Chemopreventive Agents

  • Kim, Young-Mi;Chang, Il-Moo;Mar, Woong-Chon
    • 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.

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Inhibitory Effects of Bile Acids on the Cholesterol Biosynthesis in Cultured Hepatocytes (배양 간세포내에서의 콜레스테롤 합성에 대한 담즙산의 저해효과)

  • Kim, Sung-Wan
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.21 no.5
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    • pp.496-501
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    • 1992
  • The present work tested the inhibitory effects of bile acids on the cholesterol biosynthesis and the activity of HMG-CoA reductase in cultured rat hepatocytes. The uptake of bile acids in hepatocytes were increased in according to the different bile acid concentrations and culture times. The rate of cholesterol synthesis in cells were inversely decreased to the bile acid concentrations and culture times. As expected, insulin injection (4 units/100g body weight) showed an enhancing effect of the cholesterol synthesis and the HMG-CoA reductase activity. The addition of bile acids in medium of insulin-treated hepatocytes also showed the suppressing effect. This effect was directly confirmed in isolated hepatic icrosomes by the test of HMG-CoA reductase activity. In the test of $Na^+$,$K^+$-ATPase activity in the isolated hepatocyte membrane, only the cholic acid did not stimulate the enzyme system. The reason of such difference is not obvious, but this result indicates that the cholic acid could be absorbed by simple diffusion.

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Screening of Quinone Reductase Inducers from Agricultural Byproducts Using Mouse Hepatoma Cell Line (Mouse hepatoma 세포를 이용한 농산부산물로부터 quinone reductase활성물질의 탐색)

  • Kim, Jong-Sang;Nam, Young-Jung;Kim, Joo-Won
    • Korean Journal of Food Science and Technology
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    • v.27 no.6
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    • pp.972-977
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    • 1995
  • The induction of phase II enzymes including quinone reductase [NAD(P)H dehydrogenase(quinone): NAD(P)H : (quinone acceptor) oxidoreductase, EC 1.6.99.2] is a major mechanism of whereby a large group of heterogeneous compounds prevent the toxic, mutagenic, and neoplastic effects of carcinogen. Using murine hepatoma cells(Hepalclc7 cells), quinone reductase(QR) inducers as the possible chemopreventive agents were screened from rice bran, wheat bran, soymilk residue, defatted soybean cake, defatted sesame and perilla residues. The 80% methanol extracts of defatted sesame and perilla residues induced quinone reductase significantly while the others did have little effect on the enzyme induction. Thin layer chromatography of the extracts showed that the fastest moving band(Rf=0.70) in the developing solvent of n-butanol : n-propanol : 2N ammonia(10 : 60 : 30) was responsible for the enzyme induction by the 80% methanol extracts of defatted sesame and perilla residues. Further identification of active component(s) is in progress.

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Effects of Natural Product on the Inhibition of $5{\alpha}-Reductase$ Type 2 for the Development of Chemopreventive Agents in LNCaP Cells

  • Lee, Sung-Jin;Kim, Kyeong-Ho;Cho, Myung-Haing;Lee, Sang-Kook;Mar, Woong-Chon
    • Natural Product Sciences
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    • v.5 no.2
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    • pp.97-103
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    • 1999
  • The enzyme steroid $5{\alpha}-reductase$ is responsible for the conversion of testosterone into the most potent androgen dihydrotestosterone (DHT). In man, this steroid acts on a variety of androgen-responsive target tissues to mediate such diverse endocrine processes as male sexual differentiation in the fetus and prostatic growth in men. Androgen levels in the prostate may influence carcinogenesis in this organ. The use of a $5{\alpha}-reductase$ inhibitor, finasteride, in the chemoprevention of prostate cancer is being evaluated in a clinical trial and have been used successfully for treatment of benign prostatic hyperplasia. Therefore, for the discovery of $5{\alpha}-reductase$ type 2 inhibitors, we have evaluated the inhibitory effects of solvent fractionated extracts of natural products on $5{\alpha}-reductase$ type 2 activity. We have tested approximately 80 kinds of natural products after partition into n-hexane, ethyl acetate and aqueous layers from 100% methanol extracts of plants. The ethyl acetate fractions of Perilla sikokiana $(seed,\;IC_{50}\;:\;6.2\;ug/ml)$, Sophora flavescens $(root,\;IC_{50}\;:\;8.9\;ug/ml)$, and Angelica tenuissima $(root,\;IC_{50}\;:\;11.7\;ug/ml)$ revealed inhibitory effects on $5{\alpha}-reductase$ 2 activity in LNCaP cells. The effective ethyl acetate fractions of Perilla sikokiana, Sophora flavescens, Hydnocarpus anthelmintica, and Angelica tenuissima were subfractionated by column chromatography and tested. The subfractions $F4\;(IC_{50}\;:\;1.1\;ug/ml),\;F5\;(IC_{50}\;:\;2.0\;ug/ml),\;and\;F6\;(IC_{50}\;:\;5.8\;ug/ml)$ of the ethyl acetate fraction of Perilla sikokiana and the subfraction $F8\;(IC_{50}\;:\;5.3\;ug/ml)$ of the ethyl acetate fraction of Sophora flavescens displayed greater inhibition of $5{\alpha}-reductase$ type 2 than did finasteride in LNCaP cells. These active fractions are under the process of further sequential fractionation to find the effective pure compounds against $5{\alpha}-reductase$ 2 activity.

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Screening of Phenolic Compounds with Inhibitory Activities against HMG-CoA Reductase (페놀 화합물로부터 HMG-CoA reductase 저해 활성 물질 탐색)

  • Son, Kun Ho;Lee, Ju Yeon;Lee, Jeong Soon;Kang, Sam Sik;Sohn, Ho Yong;Kwon, Chong Suk
    • Journal of Life Science
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    • v.27 no.3
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    • pp.325-333
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    • 2017
  • High level of plasma cholesterol is strongly associated with the development of atherosclerosis and coronary heart disease. Clinical trials designed to reduce plasma cholesterol level by diet or pharmacological intervention have resulted in marked reduction of disease incidence. The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase which reduces cholesterol biosynthesis in the liver is the key enzyme of the mevalonate pathway that produces cholesterol. In this study, 71 naturally occurring phenolic compounds were tested for inhibitory activities against HMG-CoA reductase. Eleven compounds out of 71 showed inhibitory activities: three hydrolyzable tannin (geraniin, acetonyl geraniin and pentagalloyl ${\beta}-D-glucose$), four benzoic acid derivatives (benzoic acid, trans-cinnamic acid, 2,4-dihydroxybenzoic acid and 2,5-dihydroxybenzoic acid), and four naphthoquinone derivatives (1,2-naphthoquinone, 1,4-naphthoquinone, plumbagin and shikonin). At the concentration of $10{\mu}g/ml$, 1,4-naphthoquinone inhibited HMG-CoA reductase by 99.4%, and then plumbagin 91.4%, pentagalloyl ${\beta}-D-glucose$ 46.6%, 2,4-dihydroxybenzoic acid 40.9%, shikonin 37.7%, 1,2-naphthoquinone 36.6%, trans-cinnamic acid 32.0%, acetonyl geraniin 30.2%, benzoic acid 28.5%, geraniin 28.3% and 2,5-dihydroxybenzoic acid 22.3%, respectively. $IC_{50}$ values of 1,4-naphthoquinone and plumbagin was $2.1{\mu}g/ml$ and $5.8{\mu}g/ml$, respectively.

Effect of p-Coumaric Acid, Benzoic Acid, and Salicylic Acid on the Activity of Glutathione Reductase and Catalase in in vitro Grown Tobacco Plants (기내배양 담배 식물에서 p-coumaric acid, benzoic acid 및 salicylic acid에 의해 유도되는 생장 및 glutathione reductase와 catalase의 활성)

  • Kim, Sang A;Roh, Kwang Soo
    • Journal of Life Science
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    • v.24 no.3
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    • pp.227-233
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    • 2014
  • Effects of p-coumaric acid (p-CA), benzoic acid (BA), and salicylic acid (SA) on the activities of glutathione reductase and catalase were studied in in vitro grown tobacco plants. After culturing the tobacco plants in MS medium containing $10^{-5}$ mM of p-CA, BA, and SA, the increase in the activities of two enzymes, glutathione reductase and catalase, were compared from day 20 to day 50 day, with an interval of 10 days. The growth of the tobacco plants treated with p-CA, BA, and SA was the highest on day 50. Analysis of the effect of the three substances on the activity of glutathione reductase showed that BA and p-CA decreased the activity of the enzyme compared with a control, and SA increased the activity of the enzyme. All of them showed the highest activity on day 40. SA increased the activity of catalase, but BA and p-CA reduced the activity of this enzyme. In all the experimental groups, the activity was the highest on day 40. In conclusion, p-CA and BA appear to promote the growth of tobacco plants. The growth was the best on day 50, but the activity of the antioxidative enzyme was inhibited. On the contrary, SA seemed to inhibit the growth of the tobacco plants but to promote the activity of glutathione reductase and catalase. The growth of the plants treated with SA was best on day 40.