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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Steinberg, D., and Witztum, J.L. (1990) Lipoprotein and Atherogenesis. JAMA 264, 3047–3052.
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.
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.
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.
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.
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.
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.
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.
Devaraj, S., Li, D., and Jialal, I. (1996) The Effects of Alpha-Tocopherol Supplementation on Monocyte Function. J. Clin. Invest. 98, 756–763.
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.
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.
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.
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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