Advertisement

Physiologic levels of ascorbate inhibit the oxidative modification of low density lipoprotein

  • Ishwarlal Jialal
    Affiliations
    Center for Human Nutrition and Departments of Clinical Nutrition, Internal Medicine, and Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, U.S.A.
    Search for articles by this author
  • Gloria Lena Vega
    Affiliations
    Center for Human Nutrition and Departments of Clinical Nutrition, Internal Medicine, and Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, U.S.A.
    Search for articles by this author
  • Scott M. Grundy
    Correspondence
    Correspondence to: Scott M. Grundy, MD, PhD, Center for Human Nutrition, Y3.206, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235, U.S.A. Phone: (214) 688-2890.
    Affiliations
    Center for Human Nutrition and Departments of Clinical Nutrition, Internal Medicine, and Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, U.S.A.
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      Oxidatively modified low density lipoprotein (LDL) could contribute to the atherosclerotic process by its cytotoxic effect, uptake by the scavenger receptor and influence on monocyte and macrophage motility. The aim of the present study was to examine the effect of physiologic levels of α-tocopherol and ascorbate on Cu2+-induced oxidative modification of LDL. Whereas α-tocopherol had an inhibitory effect on the oxidative modification of LDL only for 5 h, as evidenced by the electrophoretic mobility and lipid peroxide content, ascorbate inhibited the oxidative modification of LDL for both 5 and 24 h. By inhibiting the oxidative modification of LDL, ascorbate prevented the uptake and degradation of oxidatively modified LDL by the scavenger-receptor mechanism of cultured human monocyte derived macrophages. It thus appears that in this cell-free system (2.5 μM Cu2+), ascorbate is a more potent antioxidant than α-tocopherol. These findings indicate that ascorbate in physiologic concentrations should inhibit the oxidate modification of LDL in vivo.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Brown M.S.
        • Goldstein J.L.
        Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis.
        Annu. Rev. Biochem. 1983; 52: 223-261
        • Henriksen T.
        • Mahoney E.
        • Steinberg D.
        Enhanced macrophage degradation of low density lipoprotein previously incubated with cultured endothelial cells.
        in: 3rd edn. Proc. Nad. Acad. Sci. USA. 78. 1981: 6499
        • Steinberg D.
        • Parthasarathy S.
        • Carew T.
        • Khoo J.
        • Witztum J.
        Beyond cholesterol. Modification of low density lipoprotein that increases its atherogenicity.
        N. Engl. J. Med. 1989; 320: 915
        • Jurgens G.
        • Hoff H.
        • Chisolm G.
        • Esterbauer H.
        Modification of human serum LDL by oxidation-characterization and pathophysiological implications.
        Chem. Phys. Lipid. 1987; 45: 315
        • Hessler J.
        • Morel D.
        • Lewis L.
        • Chisolm G.
        Lipoprotein oxidation and lipoprotein induced cytotoxicity.
        Arteriosclerosis. 1983; 3: 215
        • Quinn M.
        • Parthasarathy S.
        • Fong L.
        • Steinberg D.
        Oxidatively modified LDL: a potential role in recruitment and retention of macrophages during atherogenesis.
        in: 3rd edn. Proc. Natl. Acad. Sci. U.S.A.84. 1987: 2995
        • Palinski W.
        • Rosenfeld M.
        • Ylä-Herttuala S.
        • et al.
        Low density lipoprotein undergoes oxidative modification in vivo.
        in: 3rd edn. Proc. Natl. Acad. Sci. USA. 86. 1989: 1372
        • Ylä-Herttuala S.
        • Palinski W.
        • Rosenfeld M.
        • et al.
        Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man.
        J. Clin. Invest. 1989; 84: 1086
        • Machlin L.
        Vitamin E..
        in: 3rd edn. Handbook of Vitamins. Marcel Dekker Inc, New York1984: 99-145
        • Bendich A.
        • Machlin L.J.
        • Scandurra O.
        • Burton G.W.
        • Wayner D.
        The antioxidant role of vitamin C.
        Adv. Free Radical Biol. 1986; 2: 419
        • Frei B.
        • Stocker R.
        • Ames B.N.
        Antioxidant defenses and lipid peroxidation in human blood plasma.
        in: 3rd edn. Proc. Natl. Acad. Sci. USA. 85. 1988: 9748
        • Grundy S.M.
        • Vega G.L.
        Influence of mevinolin on metabolism of low density lipoproteins in primary moderate hypercholesterolemia.
        J. Lipid Res. 1985; 26: 1464
        • Lowry O.H.
        • Rosebrough N.J.
        • Farr A.L.
        • Randall R.J.
        Protein measurement with the Folin phenol reagent.
        J. Biol. Chem. 1951; 193: 265
        • Aviram M.
        • Bierman E.L.
        • Chait A.
        Modification of low density lipoprotein by lipoprotein lipase or hepatic Lipase induces enhanced uptake and cholesterol accumulation.
        J. Biol. Chem. 1988; 263: 15416
        • Steinbreucher V.P.
        • Witztum J.
        • Parthasarathy S.
        • Steinberg D.
        Decrease in reactive amino groups during oxidation or endothelial cell modification of LDL.
        Arteriosclerosis. 1987; 7: 135
        • Heinecke J.
        • Baker L.
        • Rosen H.
        • Chait A.
        Superoxide mediated modification of LDL by arterial smooth muscle cells.
        J. Clin. Invest. 1986; 77: 757
        • Noble R.P.
        Electrophoretic separation of plasma lipoproteins in agarose gels.
        J. Lipid Res. 1968; 9: 693
        • Bierman E.L.
        • Stein O.
        • Stein Y.
        Lipoprotein uptake and metabolism by rat aortic smooth muscle cells in tissue culture.
        Circul. Res. 1974; 35: 136
        • Esterbauer H.
        • Jurgens G.
        • Quehenberger O.
        • Koller E.
        Autoxidation of human low density lipoprotein: loss of polyunsaturated fatty acids and vitamin E and generation of aldehydes.
        J. Lipid Res. 1987; 28: 495
        • Liebler D.
        • Kling D.
        • Reed D.
        Antioxidant protection of phospholipid bilayers by alpha tocopherol.
        J. Biol. Chem. 1986; 261: 12114
        • Niki E.
        Antioxidants in relation to lipid peroxidation.
        Chem. Physic. Lipids. 1987; 44: 227
        • Wayner D.
        • Burton G.W.
        • Ingold K.
        The antioxidant efficiency of vitamin C is concentration dependent.
        Biochim. Biophys. Acta. 1986; 885: 119
        • Morel D.
        • Hessler J.
        • Chisolm G.
        Low-density lipoprotein cytotoxicity induced by free radical peroxidation of lipid.
        J. Lipid Res. 1983; 24: 1070
        • Steinbrecher U.P.
        • Parthasarathy S.
        • Leake D.
        • Witztum J.
        • Steinberg D.
        Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of phospholipids.
        in: 3rd edn. Proc. Natl. Acad. Sci. USA. 81. 1984: 3883
        • van Hinsberg V.
        • Scheffer M.
        • Havekes L.
        • Kempen H.
        Role of endothelial cells and their products in the modification of LDL.
        Biochim. Biophys. Acta. 1986; 878: 49
        • Szczeklik A.
        • Gryglewski R.
        • Domagala B.
        • Dworski R.
        • Basista M.
        Dietary supplementation with vitamin E in hyperlipoproteinemias.
        Thromb. Haemost. 1985; 54: 425
        • Parthasarathy S.
        • Young S.
        • Witztum J.
        • Pittman R.
        • Steinberg D.
        Probucol inhibits oxidative modification of LDL.
        J. Clin. Invest. 1986; 77: 641
        • Lorier J.
        • Dubrenil-Quidoz S.
        • Lussier-Cacan S.
        • Huang Y.S.
        • Davignon J.
        Diet and probucol in lowering cholesterol concentrations.
        Arch. Intern. Med. 1977; 137: 1429
        • Steinberg D.
        • Parthasarathy S.
        • Carew T.
        In vivo inhibition of foam cell development by probucol in Watanabe rabbits.
        Am. J. Cardiol. 1988; 62: 6B
        • Jaffe G.M.
        Vitamin C..
        in: 3rd edn. Handbook of Vitamins. Marcel Dekker Inc, New York1984: 199-244
        • Sauberlich H.E.
        Vitamin C status: methods and findings.
        Ann. NY Acad. Sci. 1975; 258: 438
        • Case Records of the Massachusetts General Hospital
        Normal reference values.
        N. Engl. J. Med. 1986; 314: 39
        • Blake D.R.
        • Allen R.E.
        • Lune C.
        Free radicals in biological systems.
        Br. Med. Bull. 1987; 43: 371
        • Esterbauer H.
        • Striegl G.
        • Puhl H.
        • Rotheneder M.
        Continuous monitoring of in vitro oxidation of human low density lipoprotein.
        Free Radical Res. Commun. 1989; 6: 67
        • Hornig D.
        Distribution of ascorbic acid, metabolites and analogues in man and animals.
        Ann. N.Y. Acad. Sci. 1975; 258: 103