| Varying very low-density lipoprotein secretion of rat hepatocytes by altering cellular levels of calcium and the activity of protein kinase C. | |
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MedLine Citation:
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PMID: 9767371 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Calcium antagonists lower plasma levels of lipoproteins and suppress hepatic very low-density lipoprotein (VLDL) secretion. Similar effects have been observed with the calcium ionophore A23187. We studied further the effect of calcium on VLDL metabolism. METHODS: Hepatocytes from male Wistar rats were isolated and cultured in the presence or absence of calcium-mobilizing hormones, or compounds that either stimulate or inhibit the activity of protein kinase C. Secreted VLDL (d < 1.006 g mL-1) was isolated by centrifugation (145,000 x g), and lipids and apolipoprotein B were analysed. RESULTS: VLDL secretion reached maximum in hepatocytes cultured in medium containing calcium 0.8-2.4 mmolL-1. Depleting the cells of calcium by incubating in calcium-free medium or by treating the cells with the Ca(2+)-ATPase inhibitor thapsigargin (5 x 10-7 molL-1) suppressed lipid secretion to less than 15% of control, and this was accompanied by an increase in cellular levels of triacylglycerol. Calcium loading (medium calcium > 2.4 mmolL-1) suppressed both lipoprotein secretion and cellular levels of lipids, suggesting a reduced overall rate of lipid synthesis. At an extracellular calcium concentration of 0.8 mmolL-1, angiotensin II, vasopressin, endothelin-1 (10(-7) molL-1) or phenylephrine (10(-4) molL-1) suppressed VLDL secretion (maximum to 37% of control), and elevated medium calcium attenuated this effect. The protein kinase C inhibitor chelerythrine (5 x 10(-5) molL-1) and the protein kinase C activator phorbol 12-myristate 13-acetate (PMA) (10(-6) molL-1), suppressed VLDL secretion to 18% and 60% of control, respectively, whereas the protein kinase C-inactive 4 alpha-PMA was without an effect. No effect on ketogenesis was observed by these compounds, indicating that suppressed lipid secretion was not due to an enhanced oxidation of lipids. CONCLUSIONS: Hepatic VLDL secretion can be related to changes in hepatocyte levels of calcium and the activity of protein kinase C. |
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Authors:
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O G Björnsson; C S Bourgeois; G F Gibbons |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: European journal of clinical investigation Volume: 28 ISSN: 0014-2972 ISO Abbreviation: Eur. J. Clin. Invest. Publication Date: 1998 Sep |
Date Detail:
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Created Date: 1998-12-17 Completed Date: 1998-12-17 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0245331 Medline TA: Eur J Clin Invest Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 720-9 Citation Subset: IM |
Affiliation:
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Metabolic Research Laboratory University of Oxford, Radcliff Infirmary, U.K. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alkaloids Animals Benzophenanthridines Calcium / metabolism* Calcium-Transporting ATPases / antagonists & inhibitors Cells, Cultured Cholesterol / metabolism Culture Media Enzyme Activation / drug effects Enzyme Inhibitors / pharmacology Ketone Bodies / metabolism Lipid Metabolism Lipoproteins, VLDL / secretion* Liver / cytology, drug effects, physiology* Male Phenanthridines / pharmacology Phenylephrine / pharmacology Protein Kinase C / antagonists & inhibitors, metabolism* Rats Rats, Wistar Tetradecanoylphorbol Acetate / pharmacology Thapsigargin / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Alkaloids; 0/Benzophenanthridines; 0/Culture Media; 0/Enzyme Inhibitors; 0/Ketone Bodies; 0/Lipoproteins, VLDL; 0/Phenanthridines; 16561-29-8/Tetradecanoylphorbol Acetate; 34316-15-9/chelerythrine; 57-88-5/Cholesterol; 59-42-7/Phenylephrine; 67526-95-8/Thapsigargin; 7440-70-2/Calcium; EC 2.7.11.13/Protein Kinase C; EC 3.6.1.8/Calcium-Transporting ATPases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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