Source:http://linkedlifedata.com/resource/pubmed/id/10532684
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
1999-12-21
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| pubmed:abstractText |
Stimulatory effects of a novel isobenzofranone, MD-700, on low density lipoprotein (LDL) receptor activity were investigated in vitro and in vivo. MD-700 at 0.03 microg/ml elevated the expression of LDL receptor in HepG2 cells within 4 h. Corresponding to this, uptake of fluorescent labeled-LDL (3,3'-dioctadecylindocarbocyanine-LDL) by the cells increased linearly in time- and dose-dependent manner by MD-700 for up to 12 h. In the experiment using HepG2 cells transiently transfected with promoter-luciferase gene constructs, MD-700 increased luciferase activity in a dose-dependent manner from 0.03 to 0.1 microg/ml. In contrast, luciferase activity was not stimulated by MD-700 in construct with a deleted sterol regulatory element (SRE)-1, suggesting importance of SRE-1 in stimulation of the LDL receptor gene promoter by MD-700. Binding experiments on liver membranes from MD-700-treated hamsters showed about a 60% increase in 125I-labeled LDL binding. A Scatchard plot revealed that MD-700 increased the maximal binding without affecting binding affinity. In contrast to findings with an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, pravastatin, MD-700 had no effect on the sterol synthesis in hamster liver homogenates. These results suggest that MD-700 stimulates the expression of LDL receptor, presumably in a manner independent of change in sterol metabolism, and thereby promotes LDL clearance. Hypocholesterolemic actions of MD-700 in hamsters were then examined. MD-700 lowered serum cholesterol levels in hamsters fed normal chow or a high-fat diet. Fractionation of serum lipoproteins demonstrated that MD-700 selectively decreased LDL and very low density lipoprotein cholesterol. Dose-dependent decrease in serum cholesterol was also seen in hypercholesterolemic rats. Thus, the hypocholesterolemic action of MD-700 may be attributed to up-regulation of the LDL receptor, based on stimulation of the transcription of the LDL receptor gene. Although pravastatin stimulates LDL uptake and lowers serum cholesterol in a manner similar to that seen with MD-700, the mechanism responsible for hypocholesterolemic action appears to differ.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3,3'-dioctadecylindocarbocyanine,
http://linkedlifedata.com/resource/pubmed/chemical/3-hydroxy-3-methyl-1(3H)-isobenzofur...,
http://linkedlifedata.com/resource/pubmed/chemical/Benzofurans,
http://linkedlifedata.com/resource/pubmed/chemical/Carbocyanines,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorescent Dyes,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins, LDL,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins, VLDL,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, LDL,
http://linkedlifedata.com/resource/pubmed/chemical/Sterols
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
0021-9150
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
146
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
281-90
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:10532684-Animals,
pubmed-meshheading:10532684-Benzofurans,
pubmed-meshheading:10532684-Blotting, Northern,
pubmed-meshheading:10532684-Carbocyanines,
pubmed-meshheading:10532684-Carcinoma, Hepatocellular,
pubmed-meshheading:10532684-Cell Membrane,
pubmed-meshheading:10532684-Cholesterol,
pubmed-meshheading:10532684-Cricetinae,
pubmed-meshheading:10532684-DNA Primers,
pubmed-meshheading:10532684-Disease Models, Animal,
pubmed-meshheading:10532684-Fluorescent Dyes,
pubmed-meshheading:10532684-Humans,
pubmed-meshheading:10532684-Hypercholesterolemia,
pubmed-meshheading:10532684-Lipoproteins, LDL,
pubmed-meshheading:10532684-Lipoproteins, VLDL,
pubmed-meshheading:10532684-Liver Neoplasms,
pubmed-meshheading:10532684-Male,
pubmed-meshheading:10532684-Promoter Regions, Genetic,
pubmed-meshheading:10532684-RNA, Messenger,
pubmed-meshheading:10532684-RNA, Neoplasm,
pubmed-meshheading:10532684-Rats,
pubmed-meshheading:10532684-Rats, Wistar,
pubmed-meshheading:10532684-Receptors, LDL,
pubmed-meshheading:10532684-Sterols,
pubmed-meshheading:10532684-Transcription, Genetic,
pubmed-meshheading:10532684-Tumor Cells, Cultured,
pubmed-meshheading:10532684-Up-Regulation
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| pubmed:year |
1999
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| pubmed:articleTitle |
Up-regulation of low density lipoprotein receptor by a novel isobenzofranone derivative, MD-700.
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| pubmed:affiliation |
Medicinal Research Laboratories, Taisho Pharmaceutical Co. Ltd., Ohmiya, Japan. s12867@ccm.taisho.co.jp
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| pubmed:publicationType |
Journal Article,
Comparative Study
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