Document Detail


Varying very low-density lipoprotein secretion of rat hepatocytes by altering cellular levels of calcium and the activity of protein kinase C.
MedLine Citation:
PMID:  9767371     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
O G Björnsson; C S Bourgeois; G F Gibbons
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of clinical investigation     Volume:  28     ISSN:  0014-2972     ISO Abbreviation:  Eur. J. Clin. Invest.     Publication Date:  1998 Sep 
Date Detail:
Created Date:  1998-12-17     Completed Date:  1998-12-17     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0245331     Medline TA:  Eur J Clin Invest     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  720-9     Citation Subset:  IM    
Affiliation:
Metabolic Research Laboratory University of Oxford, Radcliff Infirmary, U.K.
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MeSH Terms
Descriptor/Qualifier:
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:
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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