• Title, Summary, Keyword: HMG-CoA reductase

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Regulation of HMG-CoA Reductase mRNA Stability by 25-hydroxycholesterol

  • Park, Jae-Won;Oh, Seung-Min
    • Preventive Nutrition and Food Science
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    • v.5 no.4
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    • pp.184-188
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    • 2000
  • HMG-CoA reductase is th rate-limiting enzyme of cholesterol biosynthesis. As intracellular levels of cholesterol should be regulated elaborately in response to external stimuli an internal needs, the expression of the HMG-CoA reductase gene is regulated intricately at several different levels from transcription to post-translational modification. In this study, we investigated the regulatory mechanism of HMG-CoA reductase gene expression at the post-transcriptional/pre-translational levels in a baby hamster kidney cell line, C100. when 25-hydroxycholesterol was added to cells cultured in medium containing 5% delipidized fetal bovine serum and 25$\mu$M lovastatin, the levels of HMG-CoA reductase mRNA decreased rapidly, which seemed to be due to the increased degradation of reductase mRNA. These suppressive effects of 25-hydroxycholesterol on MG-CoA reductase mRNA levels were blocked by a translation inhibitor, cycloheximide. Similarly, actinomycin D and 5,6-dichloro-1-$\beta$-D-ribofuranosylbenzimidazole, transcription inhibitors, blocked the 25-hydroxycholesterol-mediated degradation of HMG-CoA reductase mRNA. These results indicate that new protein/RNA synthesis is required for the degradation of HMG-CoA reductase mRNA. In addition, data from the transfection experiments shows that cis-acting determinants, regulating the stability of reductase mRNA, were scattered in the sequence corresponding to 1766-4313 based on the sequence of Syrian hamster HMG-CoA reductase cDNA. Our data suggests that sterol-mediated destabilization of reductase mRNA might be one of the important regulatory mechanism of HMG-CoA reductase gene expression.

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Inhibitory Effects of Transglycoslyation Products of Soy Isoflavones on Cholesterol Biosynthesis (대두 이소플라본 당전이 반응 산물의 콜레스테롤 생합성 저해 효과)

  • Yoo, Lang Kuk;Choi, Seung Jun;Moon, Tae Wha;Shim, Jae-Hoon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.2
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    • pp.293-297
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    • 2016
  • Hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) is the rate-limiting enzyme in biosynthesis of cholesterol in animals. In this study, inhibitory effects of isoflavone glycosides on HMG-CoA reductase were investigated. At sample concentration of $100{\mu}M$, genistein-7-O-triglucoside (G2-genistin) inhibited HMG-CoA reductase activity by approximately 18%, whereas daidzein-7-O-triglucoside had no inhibitory effect. In the kinetic experiments with Syrian hamster HMG-CoA reductase, G2-genistin showed inhibitory efficacy with an invariable $V_{max}$ value, suggesting that G2-genistin works as a competitive inhibitor of HMG-CoA reductase and has potential for hypocholesterolemic action through direct regulation of HMG-CoA reductase.

The Effects of Thyroid Hormone on the HMG-CoA Reductase Gene Expression

  • Choi, Jae-Won;Choi, Hong-Soon;Kim, Kyung-Hwan
    • BMB Reports
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    • v.28 no.6
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    • pp.515-522
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    • 1995
  • The effects of the thyroid hormone ($T_3$) on 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity were evaluated in a baby hamster kidney cell line, C100. The cells cultured in MEM were supplemented with 10% thyroid hormone-depleted fetal bovine serum (THDS-MEM) and had a 82.5% lower level of HMG-CoA reductase activity than the cells grown in a medium supplemented with fetal bovine serum (FBS-MEM). When $T_3$ was supplemented to THDS-MEM, the reduction of the reductase activity was blocked in a dose-dependent manner. In the cells grown in THDS-MEM containing $T_3$ at a concentration of $10^{-6}$ M, the level of HMG-CoA reductase activity was 91.8% relative to the cells grown in FBS-MEM. These changes in HMG-CoA reductase activity seemed to be at least partly due to the changes of HMG-CoA reductase mRNA levels. The level of HMG-CoA reductase mRNA in cells incubated in THDS-MEM decreased to 76.2% relative to the cells grown in FBS-MEM, while the level of reductase mRNA in cells incubated in THDS-MEM containing $T_3$ at a concentration of $10^{-6}$ M increased to 243.4% relative to the cells grown in FBS-MEM. The increase of HMG-CoA reductase mRNA level after $T_3$ treatment may have been due to the increased stability of reductase mRNA, because the transcriptional rate of the reductase gene did not change significantly in the presence or absence of $T_3$. These results indicate that $T_3$ stabilizes HMG-CoA reductase mRNA at the posttranscriptional level and regulates HMG-CoA reductase activity in a dose-dependent manner.

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THE EFFECT OF DIETARY FATS ON THE HEPATIC AND INTESTINAL 3-HYDROXY-3-METHYLGLUTARYL COENZYME A REDUCTASE ACTIVITIES IN CHICKS

  • Youn, B.S.;Tananka, K.;Ohtani, S.;Santoso, U.
    • Asian-Australasian Journal of Animal Sciences
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    • v.6 no.2
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    • pp.281-290
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    • 1993
  • This experiment was designed to evaluate the effect of degree of unsaturation (Experiment 1) and the chain length of constituent fatty acids of dietary fats (Experiment 2) on-3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activities in the liver and small intestine of chicks. Chicks were fed experimental diets for 10 days and then killed for the determination of the HMG-CoA reductase activities in the intestinal epithelial cell and hepatic microsomes. The hepatic HMG-CoA reductase activity showed the highest value in chicks fed the tallow-containing diet. Chicks fed diets containing safflower or coconut oil resulted in a significantly lower intestinal HMG-CoA reductase activity in comparison with those fed the olive oil-containing diet. The hepatic HMG-CoA reductase activity was significantly higher when fat-free and trilaurin were fed than when any other triglycerides were fed. This activity showed the lowest value in the chicks fed the diet containing tristearin. The HMG-CoA reductase activities in the jejunum and ileum were significantly or tended to be higher when trilaurin was fed than when any other triglycerides were fed. Except when trilaurin was fed, the presence of saturated fat in the diet did not have a significant effect on the intestinal HMG-CoA reductase activity, unlike the effect shown when a highly unsaturated fat was added to the diet. There was no significant correlation between the HMG-CoA reductase activities of the liver and intestinal, and the HMG-CoA reductase activity and cholesterol content of the intestinal epithelial cells.

Production of an Antihyperlipemial HMG-CoA Reductase Inhibitor from Bacillus cereus D-3 (Bacillus cereus D-3로부터 항고지혈증 HMG-CoA Reductase 저해제의 생산)

  • Lee Dae-Hyoung;Lee Jae-Won;Jeong Jae-Hong;Lee Jong-Soo
    • Microbiology and Biotechnology Letters
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    • v.34 no.1
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    • pp.52-57
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    • 2006
  • For the purpose of production of a novel antihyperlipemial HMG-CoA reductase inhibitor from bacteria, a bacterium which showed the highest HMG-CoA reductase inhibitory activity was isolated from traditional Doenjang. This strain was identified as Bacillus cereus (D-3) based on its microbiological characteristics and 165 rRNA sequence analysis. The maximal HMG-CoA reductase inhibitor production from Bacillus cereus D-3 was obtained by cultivation in a Glucose-CSL broth containing 2% glucose, 0.6% corn steep liquor, $0.04%\;K_{2}HPO_4$ and $0.05%\;KH_{2}PO_4$ at $30^{\circ}C$ for 36 h. The final HMG-CoA reductase inhibitory activity under the above conditions was 39.4%.

Screening of HMG-CoA Reductase Inhibitory Activity of Ethanol and Methanol Extracts from Cereals and Regumes (곡류 및 두류 추출물로 부터 HMG-CoA reductase 저해활성 검색)

  • Ha, Tae-Youl;Cho, Il-Jin;Lee, Sang-Hyo
    • Korean Journal of Food Science and Technology
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    • v.30 no.1
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    • pp.224-229
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    • 1998
  • A study was conducted to screen the inhibitory activity of 3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA) reductase, which is known to be rate-limiting enzyme in cholesterol bosynthesis, from the extracts of 80% methanol and 70% ethanol of cereals and regumes. The strongest inhibitory activity was shown in the ethanol extract of sorghum among the ethanol extracts. The inhibitory activity of HMG-CoA reductase of prosomillilet methanol extract was 73%, and highest among the methanol extracts. The inhibitory activity of 44.7% was observed in sorghum methanol extract. The methanol extracts of prosomillet and sorghum were further fractionated with hexane, chloroform, ethylacetate, butanol and water. HMG-CoA reductase inhibitory activity was shown in all fractions of prosomillet and sorghum methanol extracts. Hexan fraction of both prosomillet and sorghum had the strongest inhibitory activity among five fractions, and the inhibitory activity was increased compared to each crude extracts.

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Screening of Flavonoid Compounds with HMG-CoA Reductase Inhibitory Activities (플라보노이드 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.28 no.2
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    • pp.247-256
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    • 2018
  • 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are widely used drugs for lowering blood lipid levels and preventing cardiovascular diseases. HMG-CoA reductase is a key enzyme to control the biosynthesis of cholesterol. We have tested HMG-CoA reductase-inhibitory activity on the flavonoids of 98 species in vitro. The anti-hypercholesterolemic activities of flavonoids were studied using an HMG-CoA reductase assay equipped with a 96-well UV plate. This assay was based on the spectrophotometric measurement of the decrease in absorbance, which represents the oxidation of NADPH by the catalytic subunit of HMG-CoA reductase in the presence of the substrate HMG-CoA. Among the clinically available statins, pravastatin was used as a positive control. Among the tested compounds, kuraridin, morin and sophoraflavanone G showed strong inhibition activities. In particular, morin and sophoraflavanone G inhibited HMG-CoA reductase by 45.0% and 54.6% at a concentration of $10{\mu}g/ml$, and the $IC_{50}$ values were calculated to $13.31{\mu}g/ml$ and $7.26{\mu}g/ml$ respectively.

Screening of 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibitors In Vitro and Its Application to Pullets (HMG-CoA Reductase의 저해제 탐색과 가금의 콜레스테를 저하 효과)

  • Moon, Young-Ja;Yeom, Keum-Hee;Sung, Chang-Keun
    • The Korean Journal of Food And Nutrition
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    • v.15 no.4
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    • pp.307-313
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    • 2002
  • The primary objective of these studies was to screen the materials showing inhibitions of HMG-CoA reductase in vitro. The secondary objective was to determine the effect of garlic, lovastatin and copper on cholesterol concentrations in plasma, liver and breast tissues in pullets. The degree of inhibition of the selective samples on HMG-CoA reductase activity was determined in vitro. The inhibition ratios of water soluble garlic extracts, lovastatin (methanol extracts) and copper to HMG-CoA reductase activity were 51.3%, 87.5%, and 82.0%, respectively. Control diet (basal diet) and experimental diets, garlic powder (3% in diet), lovastatin (300mg/Kg of diet) and copper (200mg/Kg of diet) were fed to pullets in order to investigate the changes of cholesterol concentration in plasma and tissues. Total cholesterol, HDL- and LDL-cholesterol in blood plasma were significantly reduced in pullets fed diet containing 3% garlic powder. However, copper significantly increased total cholesterol compared to control and lovastatin did not affect plasma cholesterol concentration. Total cholesterol and triglyceride of liver and breast tissues in pullets were not affected by adding the cholesterol-lowering materials to diets. The data suggests that it is not easy for HMG-CoA reductase inhibitors to reduce cholesterol levels in body due to complication of cholesterol metabolism. However, garlic administration can lower the levels of plasma cholesterol in pullets.

Effects of Dietary Garlic Supplementation on Performance and HMG-CoA Reductase in Broiler Chicks (육계사료내 마늘의 첨가가 육계의 생산성과 HMG-CoA Reductase에 미치는 영향)

  • ;;;;S. OHTANI, K. TANAKA
    • Korean Journal of Poultry Science
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    • v.23 no.3
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    • pp.129-134
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    • 1996
  • his study was conducted to determine the effect of dietary garlic supplementation on the growing performance and activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in broiler chicks from 3 to 5 wk post hatching. Fifty chicks were divided into 5 groups with 10 replicates per treatment and placed in a wire battery cage. Five levels of dietary garlic(0, 0.1, 0.3, 0.6 and 1.0%) were provided in an one way analysis. Feed and water were given ad libitum. Feed intake, weight gain and feed conversion rate(FCR) were not affected by the garlic supplementations. The HMG-CoA reductase activity decreased significantly(P<0.05) with the supplementation of garlic powder, compared to the garlic free group. As the dietary garlic level was increased, chicks showed decreased lipid contents in liver and blood serum. The results of this study indicate that blood cholesterol of chicks fed garlic supplemented diet might be reduced by inhibition of RMG-CoA reductase activity.

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