Varying very low-density lipoprotein secretion of rat hepatocytes by altering cellular levels of calcium and the activity of protein kinase C.
| Autor: | Björnsson OG; Metabolic Research Laboratory University of Oxford, Radcliff Infirmary, U.K., Bourgeois CS, Gibbons GF |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | European journal of clinical investigation [Eur J Clin Invest] 1998 Sep; Vol. 28 (9), pp. 720-9. |
| DOI: | 10.1046/j.1365-2362.1998.00354.x |
| Abstrakt: | 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. |
| Databáze: | MEDLINE |
| Externí odkaz: |
|