| Studies of alteration of hepatic cholesterol metabolism in puromycin-induced nephrotic syndrome in rats. | |
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MedLine Citation:
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PMID: 8258956 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Hypercholesterolemia frequently accompanies the nephrotic syndrome, but the mechanism responsible for elevation of plasma cholesterol is poorly understood. Specifically, the contribution of abnormal hepatic cholesterol metabolism to elevated concentrations of serum cholesterol has never been studied in depth. The objective of the present study was to define the alteration of hepatic cholesterol metabolism in puromycin induced nephrotic syndrome in rats. Studies involved measurements of specific activities of four enzymes participating in the maintenance of hepatic cholesterol metabolism: HMG-CoA-reductase, the rate limiting enzyme of cholesterol synthesis; cholesterol 7 alpha-hydroxylase, the rate limiting enzyme in bile acid synthesis; acyl CoA: cholesterol acyltransferase, the enzyme responsible for esterification of cholesterol; and cholesterol ester hydrolase (CEH), an enzyme which hydrolyzes cholesterol. Multiple injections of puromycin resulted in a production of nephrotic syndrome with massive proteinuria, hypoalbuminemia, hypercholesterolemia, ascites and edema. HMG-CoA-reductase (nmol/hr/mg protein) and cholesterol 7 alpha-hydroxylase activities (nmol/hr/mg protein) in rats with nephrotic syndrome were not statistically significant as compared to control rats (4.0 +/- 0.7 and 2.0 +/- 0.6 vs. 3.3 +/- 0.4 and 1.6 +/- 0.2), respectively. Our results also demonstrate, for the first time, that the normal diurnal rhythm in HMG-CoA reductase activity is no longer present in the nephrotic animals. The activities in the nephrotics in the day was 4.0 nmol/hr/mg and at night, 3.9 nmol/hr/day, compared to the control values of 3.3 nmol/hr/mg in the day and 6.9 nmol/hr/mg at night. ACAT activities were 428 +/- 78 versus 302 +/- 64 pmol/min/mg/protein (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS) |
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Authors:
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M A Thabet; A Challa; J C Chan; W M Pandak; D M Heuman; Z R Vlahcevic |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Kidney international Volume: 44 ISSN: 0085-2538 ISO Abbreviation: Kidney Int. Publication Date: 1993 Oct |
Date Detail:
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Created Date: 1994-01-19 Completed Date: 1994-01-19 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0323470 Medline TA: Kidney Int Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 789-94 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, Children's Medical Center, Medical College of Virginia, Richmond. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cholesterol / metabolism* Cholesterol 7-alpha-Hydroxylase / metabolism Circadian Rhythm Female Hydroxymethylglutaryl CoA Reductases / metabolism Liver / metabolism*, ultrastructure Nephrotic Syndrome / chemically induced, enzymology, metabolism* Puromycin Rats Rats, Sprague-Dawley Sterol Esterase / metabolism Sterol O-Acyltransferase / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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DK 07526/DK/NIDDK NIH HHS; DK 31370/DK/NIDDK NIH HHS; P01 DK 38030-06/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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53-79-2/Puromycin; 57-88-5/Cholesterol; EC 1.1.1.-/Hydroxymethylglutaryl CoA Reductases; EC 1.14.13.17/Cholesterol 7-alpha-Hydroxylase; EC 2.3.1.26/Sterol O-Acyltransferase; EC 3.1.1.13/Sterol Esterase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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