Regulation of hepatic receptor-dependent degradation of LDL by mevinolin in rabbits with hypercholesterolemia induced by a wheat starch-casein diet
| Autor: | G. Marie Thompson, Yu-Sheng Chao, Alfred W. Alberts, Ting-Ting Yamin, Paulus A. Kroon |
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| Rok vydání: | 1983 |
| Předmět: |
Male
medicine.medical_specialty Very low-density lipoprotein Hypercholesterolemia Biophysics Receptors Cell Surface Lipoproteins VLDL Naphthalenes Biochemistry Endocrinology Casein Internal medicine medicine Animals Lovastatin Receptor biology Catabolism Anticholesteremic Agents Caseins Starch Hydroxymethylglutaryl-CoA reductase Diet Lipoproteins LDL Liver Receptors LDL Enzyme inhibitor LDL receptor biology.protein lipids (amino acids peptides and proteins) Rabbits Lipoprotein |
| Zdroj: | Biochimica et biophysica acta. 754(2) |
| ISSN: | 0006-3002 |
| Popis: | Rabbits fed a wheat starch-casein diet develop a marked hypercholesterolemia and have a slower rate of removal of rabbit 125 I-labeled low density lipoproteins (LDL) from plasma. Treating rabbits with mevinolin, a highly potent competitive inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, at a daily dose of 20 mg per animal prevents the increase in plasma and LDL cholesterol. The mevinolin effect is mediated through an increased rate of removal of rabbit 125 I-labeled LDL from plasma. To study the role of mevinolin on the regulation of the hepatic LDL receptor in rabbits, the binding of 125 I-labeled LDL and 125 I-labeled β-VLDL (β-Emigrating very-low-density lipoproteins) to liver membranes prepared from rabbits fed the wheat starch-casein diet with or without mevinolin was investigated. Liver membranes from wheat starch-casein-fed rabbits have no demonstrable EDTA-sensitive binding activity of 125 I-labeled LDL and low (37 ng/mg protein) binding activity of 125 I-Iabeled β-VLDL. Treatment of the wheat starch-casein fed rabbits with mevinolin results in high levels of specific EDTA-sensitive binding of 125 I-labeled LDL (28.7 ng/mg protein) and 125 I-labeled β-VLDL (120 ng/mg protein). To assess the functional role of the hepatic LDL receptor in response to mevinolin, the catabolism of 125 I-labeled LDL by perfused rabbit livers was studied. Perfused livers from mevinolin-treated rabbits show a 3.3-fold increase in the rate of receptor-dependent catabolism of 125 I-labeled LDL (4.6% · h −1 ) when compared with that of livers from rabbits not treated with mevinolin (1.4% · h −1 ). Thus, these studies demonstrate that mevinolin prevents the increase of plasma LDL cholesterol level in rabbits fed a wheat starch-casein diet by regulating the levels of hepatic LDL-binding sites and the rate of receptor-dependent catabolism of LDL by the liver. |
| Databáze: | OpenAIRE |
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