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Vitamin E reduces cholesterol esterification and uptake of acetylated low density lipoprotein in macrophages

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Lipids

Abstract

The effects of vitamin E on cholesteryl ester (CE) metabolism in 1774 cells were examined. Pretreatment of 1774 cells with vitamin E at concentrations above 50 μM significantly decreased acetylated low density lipoprotein (LDL)-induced incorporation of [14C]oleate into CF in cells in a dose-dependent manner. This was partly due to vitamin E Also significantly inhibiting the uptake of [3H]CE-labeled acetylated LDL by 1774 cells. A trend existed toward suppression of acyl-CoA:cholesterol acyltransferase (ACAT) activity in the cell lysate at high vitamin E concentration, but there was no effect on hydrolysis of CE. These data indicate that vitamin E reduces the uptake of modified LDL and suppresses ACAT activity, resulting in less cholesterol esterification in macrophages; a novel mechanism underlying the antiatherogenic properties of vitamin E.

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Abbreviations

ACAT:

acyl-CoA:cholesterol acyltransferase

ANOVA:

analysis of variance

CE:

cholesteryl ester

CHD:

coronary heart disease

DMEM:

Dulbecco's modified Fagle's medium

FBS:

Tetal bovine serum

LDL:

low density lipoprotein

LPDS:

lipoprotein-deficient serum

PBS:

Phosphate buffer saline

PKC:

protein kinase C

PMSF:

phenylmethylsulfonyl fluoride

TLC:

thin-layer chromatography

References

  1. Gey, K.F., and Puska, P. (1989) Plasma Vitamin E and A Inversely Correlated to Mortality from Ischemic Heart Disease in Cross-Cultural Epidemiology, Ann. N.Y. Acad. Sci. 570, 268–282.

    PubMed  CAS  Google Scholar 

  2. Riemersma, R.A., Wood, D.A., Macintyre, C.C.H., Elton, R.A., Gey, K.F., and Oliver, M.F. (1991) Risk of Angina Pectoris and Plasma Concentrations of Vitamins A, C, and E, and Carotene, Lancet 337, 1–5.

    Article  PubMed  CAS  Google Scholar 

  3. Stampfer, M.J., Hennekens, C.H., Manson, J.E., Colditz, G.A., Rosner, B., and Willett, W.C. (1993) Vitamin E Consumption and the Risk of Coronary Disease in Women. N. Engl. J. Med. 328, 1444–1449.

    Article  PubMed  CAS  Google Scholar 

  4. Rimm, E.B., Stampfer, M.J., Ascherio, A., Giovannucci, E., Colditz, G.A., and Willett, W.C. (1993) Vitamin E Consumption and Risk of Coronary Heart Disease in Men, N. Engl. J. Med. 328, 1450–1456.

    Article  PubMed  CAS  Google Scholar 

  5. Losonczy, K.G., Harris, T.B., and Havlik, R.J. (1996) Vitamin E and Vitamin C Supplement Use and Risk of All-Cause and Coronary Heart Disease Mortality in Older Persons: The Established Population for Epidemiological Studies of the Elderly. Am. J. Clin. Nutr. 64, 190–196.

    PubMed  CAS  Google Scholar 

  6. Hertog, M.G.L., Kromkout, D., Aravanis, C., Blackburn, H., Buzina, R., Fidanza, F., Giampaoli, S., Jansen, A., Menotii, A., Nedeljkovic, S., Pekkarinen, M., Simic, B.S., Toshima, H., Feskens, E.J.M., Hollma, P.C.H., and Katan, M.B. (1995) Flavonoid Intake and Long-Term Risk of Coronary Heart Diease and Cancer in the Seven Countries Study. Arch. Intern. Med. 155, 381–386.

    Article  PubMed  CAS  Google Scholar 

  7. Esterbauer, H., Dieber-Rotheneder, M., Striegl, G., and Waeg, G. (1991) Role of Vitamin E in Preventing the Oxidation of Low-Density Lipoprotein. Am. J. Clin. Nutr. 53, 314S-321S.

    PubMed  CAS  Google Scholar 

  8. Princen, H.M.G., van Poppel, G., Vogelezang, C., Buytenhek, R., and Kok, F.J. (1992) Supplementation with Vitamin E But Not β-Carotene in vivo Protects Low Density Lipoprotein from Lipid Peroxidation in vitro. Effect of Cigarette Smoking, Arterioscler. Thromb. 12, 554–562.

    PubMed  CAS  Google Scholar 

  9. Jialal, I., and Grundy, S.M. (1992) Effects of Dietary Supplementation with Alpha-Tocopherol on the Oxidative Modification of Low Density Lipoprotein, J. Lipid Res. 33, 899–906.

    PubMed  CAS  Google Scholar 

  10. Faruqi, R., de la Motte, C., and DiCorleto, P.E. (1994) α-Tocopherol Inhibits Agonist-Induced Monocytic Cell Adhesion to Cultured Human Endothelial Cells. J. Clin. Invest. 94, 592–600.

    PubMed  CAS  Google Scholar 

  11. Devaraj, S., Li, D., and Jialal, I. (1996) The Effects of α-Tocopherol Supplementation on Monocyte Function: Decrease Lipid Oxidation, Interleukin 1β Secretion, and Monocyte Adhesion to Endothelium. J. Clin. Invest. 98, 756–763.

    PubMed  CAS  Google Scholar 

  12. Martin, A., Foxall, T., Blumberg, J.F., and Meydani, M. (1997) Vitamin E Inhibits Low-Density Lipoprotein-Induced Adhesion of Monocytes to Human Aortic Endothelial Cells. Arterioscler. Thromb. Vasc. Biol. 17, 429–436.

    PubMed  CAS  Google Scholar 

  13. Boscoboinik D., Szewczyk, A., and Azzi, A. (1991) α-Tocopherol Regulated Vascular Smooth Muscle Cell Proliferation and Protein Kinase C Activity. Arch. Biochem. Biophys. 286, 264–269.

    Article  PubMed  CAS  Google Scholar 

  14. Tasinato, A., Boscoboinik, D., Bartoli, G.M., Maroni, P., and Azzi, A. (1995) d-α-Tocopherol Inhibition of Vascular Smooth Muscle Cell Proliferation Occurs at Physiological Concentrations, Correlates with Protein Kinase C Inhibition, and Is Independent of Its Antioxidant Properties. Proc. Natl. Acad. Sci. USA 92, 12190–12194.

    Article  PubMed  CAS  Google Scholar 

  15. Freedman, J.E., Farhat, J.H., Loscalzo, J., and Keaney, J.F. (1996) α-Tocopherol Inhibits Aggregation of Human Platelets by a Protein Kinase C-Dependent Mechanism. Circulation 94, 2434–2440.

    PubMed  CAS  Google Scholar 

  16. Rosenfeld, M.E., Tsukada, T., Gown, A.M., and Ross, R. (1987) Fatty Streak Initiation in Watanabe Heritable Hyperlipidemic and Comparably Hypercholesterolemic Fat-Fed Rabbits. Arteriosclerosis 7, 9–23.

    PubMed  CAS  Google Scholar 

  17. Steinberg, D., Parthasarathy, S., Carew, T.E., Khoo, J.C., and Witztum, J.L. (1989) Beyond Cholesterol: Modification of Low-Density Lipoprotein That Increase Its Atherogenicity, N. Engl. J. Med. 320, 915–924.

    Article  PubMed  CAS  Google Scholar 

  18. Koo, C., Wernette-Hammond, M.E., Garcia, Z., Malloy, M.J., Uauy, R., East, C., Bilheimer, D.W., Mahley, R.W., and Innerarity, T.L. (1988) Uptake of Cholesterol-Rich Remmant Lipoproteins by Human Monocyte-Derived Macrophages Is mediated by Low Density Lipoprotein Receptors. J. Clin. Invest. 81, 1332–1340.

    PubMed  CAS  Google Scholar 

  19. van der Schroeff, J.G., Havekes, L., Weerheim, A.M., Emeis, J.J., and Vermeer, B.J. (1985) Suppression of Cholesteryl Ester Accumulation in Cultured Human Monocyte-Derived Macrophages by Lipoxygenase Inhibitors. Biochem. Biophys. Res. Commun. 127, 366–372.

    Article  PubMed  Google Scholar 

  20. Suzukawa, M., Abbey, M., Clifton, P., and Nestel, P.J. (1994) Effects of Supplementing with Vitamin E on the Uptake of Low Density Lipoportein and the Stimulation of Cholesteryl Ester Formation in Macrophages, Atherosclerosis 110, 77–86

    Article  PubMed  CAS  Google Scholar 

  21. Asmis, R., Llorente, V.C., and Gey, K.F. (1995) Prevention of Cholesteryl Ester Accumulation in P388D1 Macrophage-Like Cells by Increased Cellular Vitamin E Depends on Species of Extracellular Cholesterol, Eur. J. Biochem. 233, 171–178.

    Article  PubMed  CAS  Google Scholar 

  22. Havel, R.J., Eder, H.A., and Bragdon, J.H. (1955) The Distribution and Chemical Composition of Ultracentrifugically Separated Lipoproteins in Human Serum, J. Clin. Invest. 43, 1345–1353.

    Google Scholar 

  23. Basu, S.K., Goldstein, J.L., Anderson, G.W., and Brown, M.S. (1976) Degradation of Cationized Low Density Lipoprotein and Regulation of Cholesterol Metabolism in Homozygous Familial Hypercholesterolemia Fibroblasts, Proc. Natl. Acad. Sci. USA 73, 3178–3182.

    Article  PubMed  CAS  Google Scholar 

  24. Zhang, H., Basra, H.J.K., Steinbrecher, U.P. (1991) Effects of Oxidatively Modified LDL on Cholesterol Esterification in Cultured Macrophages. J. Lipid Res. 31, 1361–1369.

    Google Scholar 

  25. Goldstein, J.L., Basu, S.K., and Brown, M.S. (1983) Receptor-Mediated Endocytosis of Low-Density Lipoprotein in Cultured Cells, Methods Enzymol. 98, 241–260.

    PubMed  CAS  Google Scholar 

  26. Lowry, O.H., Rosebrough, N.J., Farr, A.L., and Randall, R.J. (1951) Protein Measurement with the Folin Phenol Reagent. J. Biol. Chem. 193, 265–275.

    PubMed  CAS  Google Scholar 

  27. Nagayoshi, A., Matsuki, N., Saito, H., Tsukamoto, K., Wakashima, M., Kinoshita, M., Yamanaka, M., and Teramoto, T. (1994) Deficiency of Acyl CoA Cholesterol Acyltransferase Activity in Suncus Liver. J. Biochem. 115, 858–861.

    PubMed  CAS  Google Scholar 

  28. Tomita, T., Sawamura, F., Uetsuka, R., Chiba, T., Miura, S., Ikeda, M., and Tomita, I. (1996) Inhibition of Cholesteryl Ester Accumulation by 17β-Estradiol in Macrophages Through Activation of Neutral Cholesterol Esterase. Biochem. Biophys. Acta 1300, 210–218.

    PubMed  Google Scholar 

  29. Bieri, J.G., Tolliver, T.J., and Catignani, G.L. (1979) Simultaneous Determination of Alpha-Tocopherol and Retinol in Plasma or Red Cells by High Pressure Liquid Chromatography. Am. J. Clin. Nutr. 32, 2143–2149.

    PubMed  CAS  Google Scholar 

  30. Dieber-Rotheneder, M., Puhl, H., Waeg, G., Striegl, G., and Esterbauer, H. (1991) Effect of Oral Supplementation with D-α-Tocopherol on the Vitamin E Content of Human Low Density Lipoproteins and Resistance to Oxidation. J. Lipid Res. 32, 1325–1332.

    PubMed  CAS  Google Scholar 

  31. Steinberg, D., and Witztum, J.L. (1990) Lipoprotein and Atherogenesis. JAMA 264, 3047–3052.

    Article  PubMed  CAS  Google Scholar 

  32. Brown, M.S., Goldstein, J.L., Krieger, M., Ho, Y.K., and Anderson, R.G.W. (1979) Reversible Accumulation of Cholesteryl Esters in Macrophages Incubated with Acetylated Lipoproteins. J. Cell. Biol. 82, 597–613.

    Article  PubMed  CAS  Google Scholar 

  33. Parthasarathy, S., Wieland, E., and Steinberg, D. (1989) A Role for Endothelial Cell Lipoxygenase in the Oxidative Modification of Low Density Lipoprotein, Proc. Natl. Acad. Sci. USA 86, 1046–1050.

    Article  PubMed  CAS  Google Scholar 

  34. Inaba, T., Shimano, H., Gotoda, T., Harada, K., Shimada, M., Kawamura, M., Yazaki, Y., and Yamada, N. (1993) Macrophage Colony-Stimulating Factor Regulates Both Activities of Neutral and Acidic Cholesteryl Ester Hydrolase in Human Monocyte-Macrophages. J. Clin. Invest. 92, 750–757.

    PubMed  CAS  Google Scholar 

  35. Fuhrman, B., Brook, G.J., and Aviram, M. (1992) Protein Derived from Platelet α-Granules Modulate the Uptake of Oxidized Low Density Lipoprotein by Macrophages, Biochim. Biophs. Acta 1127, 15–21.

    CAS  Google Scholar 

  36. Akeson, A.L., Schroeder, K., Woods, C., Schmidt, C.J., and Jones, W.D. (1991) Suppression of Interleukin-1β and LDL Scavenger Receptor Expression in Macrophages by a Selective Protein Kinase C Inhibitor. J. Lipid Res. 32, 1699–1707.

    PubMed  CAS  Google Scholar 

  37. Mietus-Snyder, M., Friera, A., Glass, C.K., and Pitas, G.R. (1997) Regulation of Scavenger Receptor Expression in Smooth Muscle Cells by Protein Kinase C. Arterioscler. Thromb. Vasc. Biol. 17, 969–978.

    PubMed  CAS  Google Scholar 

  38. Sakamoto, W., Fujie, K., Handa, H., Ogihara, T., and Mini, M. (1990) In Vivo Inhibition of Superoxide Production and Protein Kinase C Activity in Macrophages from Vitamin E-Treated Rats, Int. J. Vitamin. Nutr. Res. 60, 338–342.

    CAS  Google Scholar 

  39. Devaraj, S., Li, D., and Jialal, I. (1996) The Effects of Alpha-Tocopherol Supplementation on Monocyte Function. J. Clin. Invest. 98, 756–763.

    Article  PubMed  CAS  Google Scholar 

  40. Dootittle, G.M., and Chang, T.Y. (1982) Acyl-CoA: Cholesterol Acyltransferase in Chinese Hamster Ovary Cells: Enzyme Activity Determined After Reconstitution in Phospholipid/Cholesterol Liposomes, Biochim. Biophys. Acta 713, 529–537.

    Google Scholar 

  41. Chang, C.C.Y., Doolittle, G.M., and Chang, T.Y. (1986) Cycloheximide Sensitivity in Regulation of Acyl Coenzyme A: Cholesterol Acyltransferase Activity in Chinese Hamster Ovary Cells. I. Effects of Exogenous Sterols. Biochemistry 25, 1693–1699.

    Article  PubMed  CAS  Google Scholar 

  42. Tabas, I., and Boykow, G.C. (1987) Protein Synthesis Inhibition in Mouse Peritoneal Macrophages Results in Increased Acyl Coenzyme A: Cholesterol Acyltransferase Activity and Cholesteryl Ester Accumulation in the Presence of Native Low Density Lipoprotein. J. Biol. Chem. 262, 12175–12181.

    PubMed  CAS  Google Scholar 

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Correspondence to Hideki Shige.

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Shige, H., Ishikawa, T., Suzukawa, M. et al. Vitamin E reduces cholesterol esterification and uptake of acetylated low density lipoprotein in macrophages. Lipids 33, 1169–1175 (1998). https://doi.org/10.1007/s11745-998-0320-9

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  • DOI: https://doi.org/10.1007/s11745-998-0320-9

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