Mechanisms for cholesterol homeostasis in rat jejunal mucosa: effects of cholesterol, sitosterol, and lovastatin
| Autor: | Sarah Shefer, Frank Ruiz, G S Tint, Gerald Salen, Lien B. Nguyen, John Bullock |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2001 |
| Předmět: |
Male
medicine.medical_specialty cholesterol uptake QD415-436 Biology Reductase Biochemistry Cholesterol Dietary Rats Sprague-Dawley Jejunum chemistry.chemical_compound Endocrinology Biosynthesis HMG-CoA reductase Microsomes Internal medicine medicine Animals Homeostasis Lovastatin chemistry.chemical_classification cholesterol absorption Cholesterol Anticholesteremic Agents LDL receptor Cell Biology Sitosterols Enzyme assay Rats LDL binding medicine.anatomical_structure Enzyme chemistry biology.protein Hydroxymethylglutaryl CoA Reductases lipids (amino acids peptides and proteins) intestinal cholesterol biosynthesis medicine.drug |
| Zdroj: | Journal of Lipid Research, Vol 42, Iss 2, Pp 195-200 (2001) |
| ISSN: | 0022-2275 |
| Popis: | The effects of feeding cholesterol, sitosterol, and lovastatin on cholesterol absorption, biosynthesis, es- terification, and LDL receptor function were examined in the rat jejunal mucosa. Cholesterol absorption was mea- sured by the dual-isotope plasma ratio method; the rate- limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3- methylglutaryl-coenzyme A (HMG-CoA) reductase, was measured as total and expressed enzyme activities (in the absence and presence of a phosphatase inhibitor, NaF, re- spectively); mucosal total and esterified cholesterol concen- trations were determined by gas-liquid chromatography; LDL receptor function was assayed as receptor-mediated binding of 125 I-labeled LDL to mucosal membranes. Feed- ing 2% sitosterol or 0.04% lovastatin for 1 week significantly ( P � 0.01) decreased the amounts of cholesterol absorbed per day ( � 85% and � 63%, respectively). In contrast, feed- ing 2% cholesterol for 1 week increased the amounts of ab- sorbed cholesterol 27-fold, even though the percent absorp- tion significantly decreased. With all three treatments, there was a coordinate regulation of total HMG-CoA reductase activity and receptor-mediated LDL binding. Cholesterol feeding downregulated both total jejunal HMG-CoA reduc- tase activity ( P � 0.05) and receptor-mediated LDL binding ( P � 0.01), whereas lovastatin- and sitosterol-supplemented diets significantly upregulated both of these parameters. In the control, cholesterol-fed, and sitosterol-fed animals, about half of the total jejunal HMG-CoA reductase activity was expressed (in functional dephosphorylated form). However, in the lovastatin-treated rats with 4-fold stimula- tion of HMG-CoA reductase, only 23% of the total enzyme activity was expressed. Changes in total HMG-CoA reduc- tase activity and receptor-mediated LDL binding in all tested groups occurred with no change in total concentra- tions of mucosal cholesterol, and only cholesterol-fed ani- mals had increased mucosal esterified cholesterol concen- trations. Thus, in response to various fluxes of dietary or newly formed cholesterol, HMG-CoA reductase and recep- tor-mediated LDL binding are coordinately regulated to maintain constant cellular cholesterol concentrations in the jejunum. —Nguyen, L. B., S. Shefer, G. Salen, G. S. Tint, F. Ruiz, and J. Bullock. Mechanisms for cholesterol homeosta- sis in rat jejunal mucosa: effects of cholesterol, sitosterol, and lovastatin. J. Lipid Res. 2001. 42: 195-200. |
| Databáze: | OpenAIRE |
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