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. 1988 Feb;85(3):885–889. doi: 10.1073/pnas.85.3.885

Low density lipoprotein causes general cellular activation with increased phosphatidylinositol turnover and lipoprotein catabolism.

L H Block 1, M Knorr 1, E Vogt 1, R Locher 1, W Vetter 1, P Groscurth 1, B Y Qiao 1, D Pometta 1, R James 1, M Regenass 1, et al.
PMCID: PMC279661  PMID: 2829208

Abstract

Low density lipoprotein (LDL), at concentrations high enough for receptor binding but not high enough to saturate the receptor, induces activation of phosphatidylinositol (PtdIns) turnover in a variety of cell types with various biological functions. Using both biochemical and electron microscopic studies, we have shown that blood platelets take up and degrade LDL in a manner reminiscent of phagocytic cell types. The activation of both PtdIns turnover and LDL metabolism is inhibited by high density lipoprotein. Thus, LDL at hormonal concentrations causes general cellular activation. Since all cell types studied responded to LDL with increased PtdIns turnover and uptake of LDL cholesterol, the PtdIns cycle may also be involved in the cellular regulation of LDL cholesterol metabolism.

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Selected References

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  1. Andrews H. E., Aitken J. W., Hassall D. G., Skinner V. O., Bruckdorfer K. R. Intracellular mechanisms in the activation of human platelets by low-density lipoproteins. Biochem J. 1987 Mar 1;242(2):559–564. doi: 10.1042/bj2420559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Angel A., D'Costa M. A., Yuen R. Low density lipoprotein binding, internalization, and degradation in human adipose cells. Can J Biochem. 1979 Jun;57(6):578–587. doi: 10.1139/o79-073. [DOI] [PubMed] [Google Scholar]
  3. Aviram M., Brook J. G. Platelet interaction with high and low density lipoproteins. Atherosclerosis. 1983 Mar;46(3):259–268. doi: 10.1016/0021-9150(83)90176-4. [DOI] [PubMed] [Google Scholar]
  4. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  5. Beg Z. H., Stonik J. A., Brewer H. B., Jr Phosphorylation of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase and modulation of its enzymic activity by calcium-activated and phospholipid-dependent protein kinase. J Biol Chem. 1985 Feb 10;260(3):1682–1687. [PubMed] [Google Scholar]
  6. Berridge M. J., Dawson R. M., Downes C. P., Heslop J. P., Irvine R. F. Changes in the levels of inositol phosphates after agonist-dependent hydrolysis of membrane phosphoinositides. Biochem J. 1983 May 15;212(2):473–482. doi: 10.1042/bj2120473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bilheimer D. W., Eisenberg S., Levy R. I. The metabolism of very low density lipoprotein proteins. I. Preliminary in vitro and in vivo observations. Biochim Biophys Acta. 1972 Feb 21;260(2):212–221. doi: 10.1016/0005-2760(72)90034-3. [DOI] [PubMed] [Google Scholar]
  8. Billah M. M., Lapetina E. G. Rapid decrease of phosphatidylinositol 4,5-bisphosphate in thrombin-stimulated platelets. J Biol Chem. 1982 Nov 10;257(21):12705–12708. [PubMed] [Google Scholar]
  9. Curtiss L. K., Plow E. F. Interaction of plasma lipoproteins with human platelets. Blood. 1984 Aug;64(2):365–374. [PubMed] [Google Scholar]
  10. Erne P., Mittelholzer E., Bürgisser E., Flückiger R., Bühler F. R. Measurement of receptor induced changes in intracellular free calcium in human platelets. J Recept Res. 1984;4(1-6):587–604. doi: 10.3109/10799898409042575. [DOI] [PubMed] [Google Scholar]
  11. Fong B. S., Rodrigues P. O., Angel A. Characterization of low density lipoprotein binding to human adipocytes and adipocyte membranes. J Biol Chem. 1984 Aug 25;259(16):10168–10174. [PubMed] [Google Scholar]
  12. Gavey K. L., Trujillo D. L., Scallen T. J. Evidence for phosphorylation/dephosphorylation of rat liver acyl-CoA:cholesterol acyltransferase. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2171–2174. doi: 10.1073/pnas.80.8.2171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. HAVEL R. J., EDER H. A., BRAGDON J. H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955 Sep;34(9):1345–1353. doi: 10.1172/JCI103182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Handley D. A., Arbeeny C. M., Witte L. D., Chien S. Colloidal gold--low density lipoprotein conjugates as membrane receptor probes. Proc Natl Acad Sci U S A. 1981 Jan;78(1):368–371. doi: 10.1073/pnas.78.1.368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Majerus P. W., Connolly T. M., Deckmyn H., Ross T. S., Bross T. E., Ishii H., Bansal V. S., Wilson D. B. The metabolism of phosphoinositide-derived messenger molecules. Science. 1986 Dec 19;234(4783):1519–1526. doi: 10.1126/science.3024320. [DOI] [PubMed] [Google Scholar]
  16. Nabika T., Velletri P. A., Beaven M. A., Endo J., Lovenberg W. Vasopressin-induced calcium increases in smooth muscle cells from spontaneously hypertensive rats. Life Sci. 1985 Aug 12;37(6):579–584. doi: 10.1016/0024-3205(85)90472-2. [DOI] [PubMed] [Google Scholar]
  17. Owen J. S., Hutton R. A., Day R. C., Bruckdorfer K. R., McIntyre N. Platelet lipid composition and platelet aggregation in human liver disease. J Lipid Res. 1981 Mar;22(3):423–430. [PubMed] [Google Scholar]
  18. Raben D. M., Cunningham D. D. Effects of EGF and thrombin on inositol-containing phospholipids of cultured fibroblasts: stimulation of phosphatidylinositol synthesis by thrombin but not EGF. J Cell Physiol. 1985 Dec;125(3):582–590. doi: 10.1002/jcp.1041250330. [DOI] [PubMed] [Google Scholar]
  19. Rink T. J., Smith S. W., Tsien R. Y. Cytoplasmic free Ca2+ in human platelets: Ca2+ thresholds and Ca-independent activation for shape-change and secretion. FEBS Lett. 1982 Nov 1;148(1):21–26. doi: 10.1016/0014-5793(82)81234-9. [DOI] [PubMed] [Google Scholar]
  20. Rittenhouse-Simmons S. Production of diglyceride from phosphatidylinositol in activated human platelets. J Clin Invest. 1979 Apr;63(4):580–587. doi: 10.1172/JCI109339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ross R. The smooth muscle cell. II. Growth of smooth muscle in culture and formation of elastic fibers. J Cell Biol. 1971 Jul;50(1):172–186. doi: 10.1083/jcb.50.1.172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schafer A. I., Maas A. K., Ware J. A., Johnson P. C., Rittenhouse S. E., Salzman E. W. Platelet protein phosphorylation, elevation of cytosolic calcium, and inositol phospholipid breakdown in platelet activation induced by plasmin. J Clin Invest. 1986 Jul;78(1):73–79. doi: 10.1172/JCI112576. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Schick B. P., Schick P. K. Cholesterol exchange in platelets, erythrocytes and megakaryocytes. Biochim Biophys Acta. 1985 Feb 8;833(2):281–290. doi: 10.1016/0005-2760(85)90200-0. [DOI] [PubMed] [Google Scholar]
  24. Schick B. P., Schick P. K. The effect of hypercholesterolemia on guinea pig platelets, erythrocytes and megakaryocytes. Biochim Biophys Acta. 1985 Feb 8;833(2):291–302. doi: 10.1016/0005-2760(85)90201-2. [DOI] [PubMed] [Google Scholar]
  25. Shattil S. J., Bennett J. S., Colman R. W., Cooper R. A. Abnormalities of cholesterol-phospholipid composition in platelets and low-density lipoproteins of human hyperbetalipoproteinemia. J Lab Clin Med. 1977 Feb;89(2):341–353. [PubMed] [Google Scholar]
  26. Slot J. W., Geuze H. J. A new method of preparing gold probes for multiple-labeling cytochemistry. Eur J Cell Biol. 1985 Jul;38(1):87–93. [PubMed] [Google Scholar]
  27. Thomas A. P., Alexander J., Williamson J. R. Relationship between inositol polyphosphate production and the increase of cytosolic free Ca2+ induced by vasopressin in isolated hepatocytes. J Biol Chem. 1984 May 10;259(9):5574–5584. [PubMed] [Google Scholar]
  28. Tsien R. Y., Pozzan T., Rink T. J. Calcium homeostasis in intact lymphocytes: cytoplasmic free calcium monitored with a new, intracellularly trapped fluorescent indicator. J Cell Biol. 1982 Aug;94(2):325–334. doi: 10.1083/jcb.94.2.325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Weber K., Osborn M. The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. J Biol Chem. 1969 Aug 25;244(16):4406–4412. [PubMed] [Google Scholar]
  30. Weisgraber K. H., Innerarity T. L., Mahley R. W. Role of lysine residues of plasma lipoproteins in high affinity binding to cell surface receptors on human fibroblasts. J Biol Chem. 1978 Dec 25;253(24):9053–9062. [PubMed] [Google Scholar]
  31. Weisweiler P., Drosner M., Janetschek P., Schwandt P. Changes in very low and low density lipoproteins with dietary fat modification. Atherosclerosis. 1983 Dec;49(3):325–332. doi: 10.1016/0021-9150(83)90143-0. [DOI] [PubMed] [Google Scholar]
  32. White J. G. A search for the platelet secretory pathway using electron dense tracers. Am J Pathol. 1970 Jan;58(1):31–49. [PMC free article] [PubMed] [Google Scholar]
  33. White J. G. Uptake of latex particles by blood platelets: phagocytosis or sequestration? Am J Pathol. 1972 Dec;69(3):439–458. [PMC free article] [PubMed] [Google Scholar]

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