| A fluorescent cholesterol analog traces cholesterol absorption in hamsters and is esterified in vivo and in vitro. | |
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MedLine Citation:
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PMID: 10508194 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The fluorescent cholesterol analog 22-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3beta-ol (fluoresterol) was characterized as a tool for exploring the biochemistry and cell biology of intestinal cholesterol absorption. Hamsters absorbed fluoresterol in a concentration- and time-dependent manner, with an efficiency of about 15-30% that of cholesterol. Fluoresterol absorption was blocked by compounds known to inhibit cholesterol absorption, implying that fluoresterol interacts with those elements of the normal pathway for cholesterol absorption on which the inhibitors act. Confocal microscopy of small intestinal tissue demonstrated that fluoresterol was taken up by absorptive epithelial cells and packaged into lipoprotein particles, suggesting a normal route of intracellular trafficking. Uptake of fluoresterol was confirmed by biochemical analysis of intestinal tissue, and a comparison of [(3)H] cholesterol and fluoresterol content in the mucosa suggested that fluoresterol moved through the enterocytes more rapidly than did cholesterol. This interpretation was supported by measurements of fluoresterol esterification in the mucosa. Four hours after hamsters were given fluoresterol and [(3)H]cholesterol orally, 44% of the fluoresterol in the intestinal mucosa was esterified, compared to 8% of the [(3)H]cholesterol. Caco-2 cells took up 2- to 5-fold more [(3)H]cholesterol than fluoresterol from bile acid micelles, and esterified 21-24% of the fluoresterol but only 1-4% of the [(3)H]cholesterol. Thus fluoresterol apparently interacts with the proteins required for cholesterol uptake, trafficking, and processing in the small intestine. |
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Authors:
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C P Sparrow; S Patel; J Baffic; Y S Chao; M Hernandez; M H Lam; J Montenegro; S D Wright; P A Detmers |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of lipid research Volume: 40 ISSN: 0022-2275 ISO Abbreviation: J. Lipid Res. Publication Date: 1999 Oct |
Date Detail:
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Created Date: 1999-12-23 Completed Date: 1999-12-23 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1747-57 Citation Subset: IM |
Affiliation:
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Department of Lipid Biochemistry, Merck Research Laboratories, Building 80W, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anticholesteremic Agents / pharmacology Bile Acids and Salts / metabolism Cholesterol / analogs & derivatives*, chemical synthesis, metabolism*, pharmacokinetics Cholesterol, Dietary / metabolism* Cricetinae Humans Intestinal Absorption* / drug effects Intestinal Mucosa / metabolism* Jejunum / physiology Kinetics Male Mesocricetus Micelles Microscopy, Confocal Microvilli / metabolism Molecular Structure Oxadiazoles / chemical synthesis, pharmacokinetics* Saponins / pharmacology Spirostans* Sterol O-Acyltransferase / metabolism Tritium Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/Anticholesteremic Agents; 0/Bile Acids and Salts; 0/Cholesterol, Dietary; 0/L 165313; 0/L 166143; 0/Micelles; 0/Oxadiazoles; 0/Saponins; 0/Spirostans; 0/fluoresterol; 10028-17-8/Tritium; 57-88-5/Cholesterol; EC 2.3.1.26/Sterol O-Acyltransferase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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