Advertisement

Interactions of Lipoproteins with Cells in Culture

  • L. Fred Roensch
  • Thomas R. Blohm

Abstract

Study of the interactions of lipoproteins with whole cells is very appropriate to the understanding of the functions and metabolism of these macromolecules. Because of their size, lipoproteins could not be expected to enter cells by simple penetration of, or solution in, the plasma membrane. Some form of specific reaction mechanism would seem to be necessary, and indeed this appears to be the case. Cell culture offers many advantages for this type of investigation. Individual cell types can be studied independently from the interactions and compensations which complicate the picture in the whole animal or even in isolated organs. Genetically mutant cells can be compared to their normal counterparts, and this approach has been most fruitful. Obviously, control of the environment is greater in cell culture than in more complex biological systems, and sampling error is lower.

Keywords

Cholesterol Synthesis Familial Hypercholesterolemia Familial Hypercholesterolemia Human Skin Fibroblast Aortic Smooth Muscle Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    G. H. Rothblat. 1972. Cellular sterol metabolism. In: Growth, Nutrition and Metabolism of Cells in Culture. Ed. by G. H. Rothblat. Academic Press, New York, p. 297.Google Scholar
  2. 2.
    G. H. Rothblat and D. Kritchevsky, eds. Lipid Metabolism in Tissue Culture Cells. 1967. Symp. No. 6. Wistar Institute, Philadelphia.Google Scholar
  3. 3.
    G. H. Rothblat. 1969. Lipid metabolism in tissue culture cells. In: Advances in Lipid Research, Vol. 7. Ed. by R. Paoletti and D. Kritchevsky. Academic Press, New York, London, p. 135.Google Scholar
  4. 4.
    O. J. Pollak. 1969. Tissue Cultures, Vol. 1. Williams and Wilkins, Baltimore.Google Scholar
  5. 5.
    M.D. Siperstein. 1970. Regulation of cholesterol biosynthesis in normal and malignant tissues. Curr. Top. Cell Regal. 2:65–100.Google Scholar
  6. 6.
    J. M. Bailey. 1966. Lipid metabolism in cultured cells. VI. Lipid biosynthesis in serum and synthetic growth media. Biochim. Biophys. Acta 125:226–236.Google Scholar
  7. 7.
    J. Avigan, S. J. Bhathena, C. D. Williams, and M. E. Schreiner. 1972. I. In vitro biosynthesis of lipids, proteins and deoxyribonucleic acid in aortic tissue and in cultured aortic cells. Biochim. Biophys. Acta 270:279–287.PubMedGoogle Scholar
  8. 8.
    J. Avigan, C. D. Williams, and J. P. Blass. 1970. Regulation of sterol synthesis in human skin fibroblast cultures. Biochim. Biophys. Acta 218:381–384.Google Scholar
  9. 9.
    M. S. Brown, S. E. Dana, and J. L. Goldstein. 1973. Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in human fîbroblasts by lipoproteins. Proc. Natl. Acad. Sci. U.S.A. 70:2162–2166.PubMedCrossRefGoogle Scholar
  10. 10.
    C. D. Williams and J. Avigan. 1972. In vitro effects of serum proteins and lipids on lipid synthesis in human skin fibroblasts and leucocytes grown in culture. Biochim. Biophys. Acta 260:413–423.PubMedGoogle Scholar
  11. 11.
    M. D. Brown, S. E. Dana, and J. L. Goldstein. 1974. Regulation of 3-hydroxy-3-methylgultaryl coenzyme A reductase activity in cultured human fibroblasts. J. Biol. Chem. 249:789–796.PubMedGoogle Scholar
  12. 12.
    M. S. Brown, S. E. Dana, J. M. Dietschy, and M. D. Siperstein. 1973. 3-Hydroxy-3-methylglutaryl coenzyme A reductase. J. Biol. Chem. 248:4731–4738.PubMedGoogle Scholar
  13. 13.
    J. L. Goldstein and M. S. Brown. 1973. Familial hypercholesterolemia: Identification of a defect in the regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity associated with overproduction of cholesterol. Proc. Natl. Acad. Sci. U.S.A. 70:2804–2808.PubMedCrossRefGoogle Scholar
  14. 14.
    M. S. Brown and J. L. Goldstein. 1974. Familial hypercholesterolemia: Defective binding of lipoproteins to cultured fibroblasts associated with impaired regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. Proc. Natl. Acad. Sci. U.S.A. 71:788–792.PubMedCrossRefGoogle Scholar
  15. 15.
    J. L. Goldstein and M. S. Brown. 1974. Binding and degradation of low density lipoproteins by cultured human fibroblasts. J. Biol. Chem. 249:5153–5162.PubMedGoogle Scholar
  16. 16.
    T. Langer, W. Strober, and R. I. Levy. 1972. The metabolism of low-density lipoprotein in familial Type II hyperlipoproteinemia. J. Clin. Invest. 51:1528–1536.PubMedCrossRefGoogle Scholar
  17. 17.
    A. D. Sniderman, T. E. Carew, J. G. Chandler, and D. Steinberg. 1974. Paradoxical increase in rate of catabolism of low density lipoproteins after hepatectomy. Science 183:526–528.PubMedCrossRefGoogle Scholar
  18. 18.
    J. L. Goldstein, S. E. Dana, and M. S. Brown. 1974. Esterification of low-density lipoprotein cholesterol in human fîbroblasts and its absence in homozygous familial hypercholesterolemia. Proc. Natl. Acad. Sci. U.S.A. 71:4288–4292.PubMedCrossRefGoogle Scholar
  19. 19.
    M. S. Brown, S. E. Dana, and J. L. Goldstein. 1975. Receptor-dependent hydrolysis of cholesteryl esters contained in plasma low density lipoprotein. Biochemistry 72:2925–2929.Google Scholar
  20. 20.
    M. S. Brown, S. E. Dana, and J. L. Goldstein. 1975. Cholesterol ester formation in cultured human fibroblasts. J. Biol. Chem. 250:4025–4027.PubMedGoogle Scholar
  21. 21.
    J. L. Goldstein, G. Y. Brunschede, and M. S. Brown. 1975. Inhibition of the proteolytic degradation of low density lipoprotein in human fibroblasts by chloroquine, con-canavalin A, and Triton WR 1339. J. Biol. Chem. 250:7854–7862.PubMedGoogle Scholar
  22. 22.
    M. S. Brown and J. L. Goldstein. 1975. Regulation of the activity of the low density lipoprotein receptor in human fibroblasts. Cell 6:307–316.PubMedCrossRefGoogle Scholar
  23. 23.
    H. W. Chen, A. A. Kandutsch, and C. Waymouth. 1974. Inhibition of cell growth by oxygenated derivatives of cholesterol. Nature 251:419–421.PubMedCrossRefGoogle Scholar
  24. 24.
    M. S. Brown and J. L. Goldstein. 1974. Suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and inhibition of growth of human fibroblasts by 7-ketocholesterol. J. Biol. Chem. 249:7306–7314.PubMedGoogle Scholar
  25. 25.
    A. A. Kandutsch and H. W. Chen. 1974. Inhibition of sterol synthesis in cultured mouse cells by cholesterol derivatives oxygenated in the side chain. J. Biol. Chem. 249:6057–6061.PubMedGoogle Scholar
  26. 26.
    J. L. Breslow, D. A. Lothrop, D. R. Spaulding, and A. A. Kandutsch. 1975. Cholesterol, 7-ketocholesterol and 25-hydroxycholesterol uptake studies and effect on 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in human fibroblasts. Biochim. Biophys. Acta 398:10–17.PubMedGoogle Scholar
  27. 27.
    M. D. Haust and R. H. More. 1971. Development of modern theories on the pathogenesis of atherosclerosis. In: The Pathogenesis of Atherosclerosis. Ed. by R. W. Wissler and J. C. Geer. Williams and Wilkins, Baltimore, pp. 1–19.Google Scholar
  28. 28.
    J. C. Geer and W. S. Webster. 1973. Morphology of mesenchymal elements of normal artery, fatty streaks and plaques. Adv. Exp. Biol. Med. 43:9–31.Google Scholar
  29. 29.
    O. Stein and Y. Stein. 1975. Surface binding and interiorization of homologous and heterologous serum lipoproteins by rat aortic smooth muscle cells in culture. Biochim. Biophys. Acta 398:377–384.PubMedGoogle Scholar
  30. 30.
    J. L. Goldstein and M. S. Brown. 1975. Lipoprotein receptors, cholesterol metabolism, and atherosclerosis. Arch. Pathol. 99:181–184.PubMedGoogle Scholar
  31. 31.
    M. S. Brown, J. R. Faust, and J. L. Goldstein. 1975. Role of the low density lipoprotein receptor in regulating the content of free and esterified cholesterol in human fibroblasts. J. Clin. Invest. 55:783–793.PubMedCrossRefGoogle Scholar
  32. 32.
    O. Stein and Y. Stein. 1975. Comparative uptake of rat and human serum low-density and high-density lipoproteins by rat aortic smooth muscle cells in culture. Circ. Res. 36:436–443.PubMedGoogle Scholar
  33. 33.
    E. L. Bierman and J. J. Albers. 1975. Lipoprotein uptake by cultured human arterial smooth muscle cells. Biochim. Biophys. Acta 388:198–202.PubMedGoogle Scholar
  34. 34.
    G. Assmann, B. G. Brown, and R. W. Mahley. 1975. Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in cultured swine aortic smooth muscle cells by plasma lipoproteins. Biochemistry 14:3996–4002.CrossRefGoogle Scholar
  35. 35.
    R. W. Mahley, T. P. Bersot, M. S. Brown, and J. L. Goldstein. 1975. Regulation of sterol metabolism in fibroblasts by a swine lipoprotein lacking apo-B. Circulation 52(Suppl II):60.Google Scholar
  36. 36.
    R. J. Havel and J. P. Kane. 1973. Primary dysbetalipoproteinemia: Predominance of a specific apoprotein species in triglyceride-rich lipoproteins. Proc. Natl. Acad. Sci. U.S.A. 70:2015–2019.PubMedCrossRefGoogle Scholar
  37. 37.
    C. H. Burns and G. H. Rothblat. 1969. Cholesterol excretion by tissue culture cells: Effect of serum lipids. Biochim. Biophys. Acta 176:616–625.PubMedGoogle Scholar
  38. 38.
    Y. Stein, M. C. Glangeaud, M. Fainaru, and O. Stein. 1975. The removal of cholesterol from aortic smooth muscle cells in culture and Landschutz ascites cells by fractions of human high-density apolipoprotein. Biochim. Biophys. Acta 380:106–118.PubMedGoogle Scholar
  39. 39.
    J. F. Mustard and M. A. Packham. 1971. Role of platelets and thrombosis in atherosclerosis. In: The Platelet. Ed. by K. M. Brinkhous, P. N. Shermer and F. K. Mostofi. Williams and Wilkins, Baltimore, pp. 215–232.Google Scholar
  40. 40.
    S. N. Jagannathan, L. J. Lewis, and W. E. Connor. 1974. The accumulation of free and esterified cholesterol by human endothelial cells cultured with various plasma lipoproteins. Circulation 50(Suppl III):69.Google Scholar
  41. 41.
    R. M. Chen, G. S. Getz, K. Fisher-Dzoga and R. W. Wissler. 1974. Comparison of the effects of hyperlipemic serum on the lipid metabolism of rabbit aortic medial cells, rabbit skin fibroblasts and mouse L-cell fibroblasts. Circulation 50(Suppl III):71.Google Scholar
  42. 42.
    E. S. Kirsten and J. A. Watson. 1974. Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in hepatoma tissue culture cells by serum lipoproteins. J. Biol. Chem. 249:6104–6109.PubMedGoogle Scholar
  43. 43.
    F. O. Nervi and J. M. Dietschy. 1974. Inhibition of hepatic cholesterogenesis by different lipoproteins. Circulation 50(Suppl III):46.Google Scholar
  44. 44.
    R. A. Florentin, S. C. Nam, J. M. Reiner, K. T. Lee, and W. A. Thomas. 1971. Arterial cell population kinetics and cholesterol. Circulation 44(Suppl II):6.Google Scholar
  45. 45.
    H. C. Stary and G. C. McMillan. 1970. Kinetics of cellular proliferation in experimental atherosclerosis. Arch. Pathol. 89:173–183.PubMedGoogle Scholar
  46. 46.
    A. L. Myasnikov and Y. E. Block. 1965. Influence of some factors on lipoidosis and cell proliferation in aorta tissue cultures of adult rabbits. J. Atheroscler. Res. 5:33–42.PubMedCrossRefGoogle Scholar
  47. 47.
    V. C. Y. Kao, R. W. Wissler, and K. Dzoga. 1968. The influence of hyperlipemic serum on the growth of medial smooth cells of rhesus monkey aorta in vitro. Circulation 38(Suppl VI):12.Google Scholar
  48. 48.
    R. A. Florentin, B. H. Choi, K. T. Lee, and W. A. Thomas. 1969. Stimulation of DNA synthesis and cell division in vitro by serum from cholesterol-fed swine. J. Cell Biol. 41:641–645.PubMedCrossRefGoogle Scholar
  49. 49.
    A. S. Daoud, K. E. Fritz, and J. Jarmolych. 1970. Increased DNA synthesis in aortic expiants from swine fed a high-cholesterol diet. Exp. Mol. Pathol. 13:377–384.PubMedCrossRefGoogle Scholar
  50. 50.
    K. Dzoga, R. W. Wissler, and D. Vesselinovitch. 1971. The effect of normal and hyperlipemic low density lipoprotein fractions on aortic tissue culture cells. Circulation 44(Suppl II):6.Google Scholar
  51. 51.
    K. Dzoga, D. Vesselinovitch, R. Fraser, and R. W. Wissler. 1971. The effect of lipoproteins on the growth of aortic smooth muscle cells in vitro. Am. J. Pathol. 62:32a.Google Scholar
  52. 52.
    K. Fisher-Dzoga, R. W. Wissler, and A. M. Scanu. 1974. Increased cell proliferation of aortic smooth muscle cells induced by varying degrees of hyperlipemia and by lipoprotein fractions. Circulation 50(Suppl III):263.Google Scholar
  53. 53.
    K. Fisher-Dzoga. 1975. Primary cultures of arterial smooth muscle cells in normal and hyperlipemic serum. In Vitro 10:359.Google Scholar
  54. 54.
    K. Fisher-Dzoga, R. M. Jones, D. Vesselinovitch, and R. W. Wissler. 1973. Increased mitotic activity in primary cultures of aortic smooth muscle cells after exposure to hyperlipemic serum. In: Atherosclerosis, Proceedings of the Third International Symposium. Ed. by G. Schettler and A. Weizel, Springer-Verlag, New York, p. 193.Google Scholar
  55. 55.
    K. Fisher-Dzoga, R. Chen, and R. W. Wissler. 1973. Effects of serum lipoproteins on the morphology, growth and metabolism of arterial smooth muscle cells. Adv. Exp. Med. Biol. 43:299–311.Google Scholar
  56. 56.
    B. G. Brown and R. W. Mahley. 1974. Stimulation of growth of swine lipoproteins in tissue culture. Circulation 50(Suppl III):70.Google Scholar
  57. 57.
    R. Ross and J. A. Glomset. 1973. Atherosclerosis and the arterial smooth muscle cell. Science 180:1332–1339.PubMedCrossRefGoogle Scholar
  58. 58.
    R. Ross, J. Glomset, B. Kariya, and L. Harker. 1974. A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro. Proc. Natl. Acad. Sci. U.S.A. 71:1207–1210.PubMedCrossRefGoogle Scholar
  59. 59.
    B. H. Choi, R. A. Florentin, and S. K. Lee. 1968. Damaging effect of hypercholes-terolemic swine serum in tissue culture. Fed. Proc. 27:575.Google Scholar
  60. 60.
    R. M. Chen, G. S. Getz, K. Fisher-Dzoga, and R. W. Wissler. 1974. Effects of hyper-lipemic serum on proliferation and detachment rate of rabbit aortic medial cells. Fed. Proc. 33:623.Google Scholar
  61. 61.
    H. W. Chen, H. Heiniger, and A. A. Kandutsch. 1975. Relationship between sterol synthesis and DNA synthesis in phytohemagglutinin-stimulated mouse lymphocytes. Proc. Natl. Acad. Sci. U.S.A. 72:1950–1954.PubMedCrossRefGoogle Scholar
  62. 62.
    R. F. Scott, J. Jarmolych, K. E. Fritz, H. Imai, D. N. Kim, and E. S. Morrison. 1970. Reactions of endothelial and smooth muscle cells in the atherosclerotic lesion. In: Atherosclerosis, Proceedings of the Second International Symposium. Ed. by R. J. Jones. Springer-Verlag, New York, pp. 50–58.Google Scholar
  63. 63.
    J. Lindner. 1969. Histochemistry. In: Atherosclerosis, Pathology, Physiology, Etiology, Diagnosis and Clinical Management. Ed. by G. Schettler, and G. S. Boyd. Elsevier, Amsterdam, pp. 73–140.Google Scholar
  64. 64.
    M. Higgins and H. Rudney. 1973. Regulation of rat liver β-hydroxy-β-methylglutaryl CoA reductase activity by cholesterol. Nature (London), New Biol. 249:60–61.Google Scholar
  65. 65.
    P. A. Edwards and R. B. Gould. 1972. Turnover rate of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase as determined by use of cyloheximide. J. Biol. Chem. 247:1520–1525.PubMedGoogle Scholar
  66. 66.
    E. P. Benditt and J. M. Benditt. 1973. Evidence for a monoclonal origin of human atherosclerotic plaques. Proc. Natl. Acad. Sci. U.S.A. 70:1753–1756.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1976

Authors and Affiliations

  • L. Fred Roensch
    • 1
  • Thomas R. Blohm
    • 1
  1. 1.Division of Richardson-Merrell, Inc.Merrell-National LaboratoriesCincinnatiUSA

Personalised recommendations