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. 1989 Sep 1;262(2):425–429. doi: 10.1042/bj2620425

Glucagon, cyclic AMP and adrenaline stimulate the degradation of low-density lipoprotein by cultured rat hepatocytes.

N F Brown 1, A M Salter 1, R Fears 1, D N Brindley 1
PMCID: PMC1133285  PMID: 2552996

Abstract

Rat hepatocytes were preincubated for 16 h with hormones or drugs and then for a further 8 h with 125I-human low-density lipoprotein (LDL). Glucagon (via cyclic AMP) and adrenaline (via cyclic AMP and alpha-effects) increased the binding of 125I-LDL to the LDL receptor, and the degradation of LDL to [125I]iodotyrosine. The effects on degradation were antagonized by dexamethasone, and the action of cyclic AMP on binding and degradation was inhibited by actinomycin D. The results are discussed in relation to the control of lipoprotein metabolism in diabetes.

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Selected References

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  1. Bartlett S. M., Gibbons G. F. Short- and longer-term regulation of very-low-density lipoprotein secretion by insulin, dexamethasone and lipogenic substrates in cultured hepatocytes. A biphasic effect of insulin. Biochem J. 1988 Jan 1;249(1):37–43. doi: 10.1042/bj2490037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beg Z. H., Allmann D. W., Gibson D. M. Modulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity with cAMP and wth protein fractions of rat liver cytosol. Biochem Biophys Res Commun. 1973 Oct 15;54(4):1362–1369. doi: 10.1016/0006-291x(73)91137-6. [DOI] [PubMed] [Google Scholar]
  3. Bernini F., Corsini A., Allorio M., Musanti R., Fumagalli R. Lipophilic beta-adrenoceptor antagonists stimulate low density lipoprotein receptor activity in human skin fibroblasts. Pharmacology. 1987;34(4):225–232. doi: 10.1159/000138272. [DOI] [PubMed] [Google Scholar]
  4. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  5. Bricker L. A., Levey G. S. Evidence for regulatin of cholesterol and fatty acid synthesis in liver by cyclic adenosine 3',5'-monophosphate. J Biol Chem. 1972 Aug 10;247(15):4914–4915. [PubMed] [Google Scholar]
  6. Brindle N. P., Ontko J. A. Alpha-adrenergic suppression of very-low-density-lipoprotein triacylglycerol secretion by isolated rat hepatocytes. Biochem J. 1988 Mar 1;250(2):363–368. doi: 10.1042/bj2500363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brindley D. N., Brown N. F., Salter A. M., Fisher S. C., Fears R. Role of insulin and counter-regulatory hormones in the control of hepatic glycerolipid synthesis and low-density-lipoprotein catabolism in diabetes. Biochem Soc Trans. 1989 Feb;17(1):43–46. doi: 10.1042/bst0170043. [DOI] [PubMed] [Google Scholar]
  8. Brown M. S., Goldstein J. L. Regulation of the activity of the low density lipoprotein receptor in human fibroblasts. Cell. 1975 Nov;6(3):307–316. doi: 10.1016/0092-8674(75)90182-8. [DOI] [PubMed] [Google Scholar]
  9. Cascales C., Mangiapane E. H., Brindley D. N. Oleic acid promotes the activation and translocation of phosphatidate phosphohydrolase from the cytosol to particulate fractions of isolated rat hepatocytes. Biochem J. 1984 May 1;219(3):911–916. doi: 10.1042/bj2190911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Durrington P. N., Newton R. S., Weinstein D. B., Steinberg D. Effects of insulin and glucose on very low density lipoprotein triglyceride secretion by cultured rat hepatocytes. J Clin Invest. 1982 Jul;70(1):63–73. doi: 10.1172/JCI110604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gibbons G. F. Hyperlipidaemia of diabetes. Clin Sci (Lond) 1986 Nov;71(5):477–486. doi: 10.1042/cs0710477. [DOI] [PubMed] [Google Scholar]
  12. Gibbons G. F., Pullinger C. R. Regulation of hepatic very-low-density lipoprotein secretion in rats fed on a diet high in unsaturated fat. Biochem J. 1987 Apr 15;243(2):487–492. doi: 10.1042/bj2430487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Goldstein J. L., Basu S. K., Brown M. S. Receptor-mediated endocytosis of low-density lipoprotein in cultured cells. Methods Enzymol. 1983;98:241–260. doi: 10.1016/0076-6879(83)98152-1. [DOI] [PubMed] [Google Scholar]
  14. Golos T. G., August A. M., Strauss J. F., 3rd Expression of low density lipoprotein receptor in cultured human granulosa cells: regulation by human chorionic gonadotropin, cyclic AMP, and sterol. J Lipid Res. 1986 Oct;27(10):1089–1096. [PubMed] [Google Scholar]
  15. Golos T. G., Soto E. A., Tureck R. W., Strauss J. F., 3rd Human chorionic gonadotropin and 8-bromo-adenosine 3',5'-monophosphate stimulate [125I]low density lipoprotein uptake and metabolism by luteinized human granulosa cells in culture. J Clin Endocrinol Metab. 1985 Oct;61(4):633–638. doi: 10.1210/jcem-61-4-633. [DOI] [PubMed] [Google Scholar]
  16. Havekes L. M., Schouten D., de Wit E. C., Cohen L. H., Griffioen M., van Hinsbergh V. W., Princen H. M. Stimulation of the LDL receptor activity in the human hepatoma cell line Hep G2 by high-density serum fractions. Biochim Biophys Acta. 1986 Feb 12;875(2):236–246. doi: 10.1016/0005-2760(86)90173-6. [DOI] [PubMed] [Google Scholar]
  17. Havel R. J. George Lyman Duff memorial lecture. Role of the liver in atherosclerosis. Arteriosclerosis. 1985 Nov-Dec;5(6):569–580. doi: 10.1161/01.atv.5.6.569. [DOI] [PubMed] [Google Scholar]
  18. Heimberg M., Olubadewo J. O., Wilcox H. G. Plasma lipoproteins and regulation of hepatic metabolism of fatty acids in altered thyroid states. Endocr Rev. 1985 Fall;6(4):590–607. doi: 10.1210/edrv-6-4-590. [DOI] [PubMed] [Google Scholar]
  19. Howard B. V. Lipoprotein metabolism in diabetes mellitus. J Lipid Res. 1987 Jun;28(6):613–628. [PubMed] [Google Scholar]
  20. Kempen H. J. Lipoprotein secretion by isolated rat hepatocytes: characterization of the lipid-carrying particles and modulation of their release. J Lipid Res. 1980 Aug;21(6):671–680. [PubMed] [Google Scholar]
  21. Kovanen P. T., Brown M. S., Goldstein J. L. Increased binding of low density lipoprotein to liver membranes from rats treated with 17 alpha-ethinyl estradiol. J Biol Chem. 1979 Nov 25;254(22):11367–11373. [PubMed] [Google Scholar]
  22. Kovanen P. T. Regulation of plasma cholesterol by hepatic low-density lipoprotein receptors. Am Heart J. 1987 Feb;113(2 Pt 2):464–469. doi: 10.1016/0002-8703(87)90615-6. [DOI] [PubMed] [Google Scholar]
  23. Leren T. P. Doxazosin increases low density lipoprotein receptor activity. Acta Pharmacol Toxicol (Copenh) 1985 Mar;56(3):269–272. doi: 10.1111/j.1600-0773.1985.tb01288.x. [DOI] [PubMed] [Google Scholar]
  24. Mangiapane E. H., Brindley D. N. Effects of dexamethasone and insulin on the synthesis of triacylglycerols and phosphatidylcholine and the secretion of very-low-density lipoproteins and lysophosphatidylcholine by monolayer cultures of rat hepatocytes. Biochem J. 1986 Jan 1;233(1):151–160. doi: 10.1042/bj2330151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Maziere C., Maziere J. C., Salmon S., Auclair M., Mora L., Moreau M., Polonovski J. Cyclic AMP decreases LDL catabolism and cholesterol synthesis in the human hepatoma cell line HepG2. Biochem Biophys Res Commun. 1988 Oct 14;156(1):424–431. doi: 10.1016/s0006-291x(88)80858-1. [DOI] [PubMed] [Google Scholar]
  26. Mazière J. C., Mazière C., Gardette J., Mora L., Polonovski J. Effect of cyclic AMP on low density lipoprotein binding and internalization by cultured human fibroblasts. Biochem Biophys Res Commun. 1983 May 16;112(3):795–800. doi: 10.1016/0006-291x(83)91687-x. [DOI] [PubMed] [Google Scholar]
  27. Patsch W., Franz S., Schonfeld G. Role of insulin in lipoprotein secretion by cultured rat hepatocytes. J Clin Invest. 1983 May;71(5):1161–1174. doi: 10.1172/JCI110865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pullinger C. R., Gibbons G. F. Effects of hormones and pyruvate on the rates of secretion of very-low-density lipoprotein triacylglycerol and cholesterol by rat hepatocytes. Biochim Biophys Acta. 1985 Jan 9;833(1):44–51. doi: 10.1016/0005-2760(85)90251-6. [DOI] [PubMed] [Google Scholar]
  29. Salter A. M., Bugaut M., Saxton J., Fisher S. C., Brindley D. N. Effects of preincubation of primary monolayer cultures of rat hepatocytes with low- and high-density lipoproteins on the subsequent binding and metabolism of human low-density lipoprotein. Biochem J. 1987 Oct 1;247(1):79–84. doi: 10.1042/bj2470079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Salter A. M., Fisher S. C., Brindley D. N. Binding of low-density lipoprotein to monolayer cultures of rat hepatocytes is increased by insulin and decreased by dexamethasone. FEBS Lett. 1987 Aug 10;220(1):159–162. doi: 10.1016/0014-5793(87)80895-5. [DOI] [PubMed] [Google Scholar]
  31. Salter A. M., Fisher S. C., Brindley D. N. Interactions of triiodothyronine, insulin and dexamethasone on the binding of human LDL to rat hepatocytes in monolayer culture. Atherosclerosis. 1988 May;71(1):77–80. doi: 10.1016/0021-9150(88)90304-8. [DOI] [PubMed] [Google Scholar]
  32. Salter A. M., Saxton J., Brindley D. N. Characterization of the binding of human low-density lipoprotein to primary monolayer cultures of rat hepatocytes. Biochem J. 1986 Dec 1;240(2):549–557. doi: 10.1042/bj2400549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Scarabottolo L., Trezzi E., Roma P., Catapano A. L. Experimental hypothyroidism modulates the expression of the low density lipoprotein receptor by the liver. Atherosclerosis. 1986 Mar;59(3):329–333. doi: 10.1016/0021-9150(86)90129-2. [DOI] [PubMed] [Google Scholar]
  34. Schonfeld G., Pfleger B., Needleman P., Kipnis D. Indomethacin inhibits the cellular receptor-dependent processing of low density lipoproteins; cyclic nucleotides have no effect. J Clin Endocrinol Metab. 1980 Sep;51(3):662–668. doi: 10.1210/jcem-51-3-662. [DOI] [PubMed] [Google Scholar]
  35. Sparks C. E., Sparks J. D., Bolognino M., Salhanick A., Strumph P. S., Amatruda J. M. Insulin effects on apolipoprotein B lipoprotein synthesis and secretion by primary cultures of rat hepatocytes. Metabolism. 1986 Dec;35(12):1128–1136. doi: 10.1016/0026-0495(86)90026-0. [DOI] [PubMed] [Google Scholar]
  36. Stout R. W., Bierman E. L. Dibutyryl cyclic AMP inhibits LDL binding in cultured fibroblasts and arterial smooth muscle cells. Atherosclerosis. 1983 Jan;46(1):13–20. doi: 10.1016/0021-9150(83)90159-4. [DOI] [PubMed] [Google Scholar]
  37. Taylor R., Agius L. The biochemistry of diabetes. Biochem J. 1988 Mar 15;250(3):625–640. doi: 10.1042/bj2500625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Wade D. P., Knight B. L., Soutar A. K. Binding of low-density lipoprotein and chylomicron remnants to the hepatic low-density lipoprotein receptor of dogs, rats and rabbits demonstrated by ligand blotting. Failure to detect a distinct chylomicron-remnant-binding protein by ligand blotting. Eur J Biochem. 1986 Sep 1;159(2):333–340. doi: 10.1111/j.1432-1033.1986.tb09872.x. [DOI] [PubMed] [Google Scholar]
  39. Wade D. P., Knight B. L., Soutar A. K. Hormonal regulation of low-density lipoprotein (LDL) receptor activity in human hepatoma Hep G2 cells. Insulin increases LDL receptor activity and diminishes its suppression by exogenous LDL. Eur J Biochem. 1988 May 16;174(1):213–218. doi: 10.1111/j.1432-1033.1988.tb14084.x. [DOI] [PubMed] [Google Scholar]
  40. Walton K. W., Scott P. J., Dykes P. W., Davies J. W. The significance of alterations in serum lipids in thyroid dysfunction. II. Alterations of the metabolism and turnover of 131-I-low-density lipoproteins in hypothyroidism and thyrotoxicosis. Clin Sci. 1965 Oct;29(2):217–238. [PubMed] [Google Scholar]

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