Functional Properties of Modified Low Density Lipoprotein and Degradation of Modified LDL by Human Monocyte-Macrophages

  • Published : 1995.06.01

Abstract

Human plasma low density lipoprotein(LDL) is the main carrier for cholesterol, and recent studies suggest the normal LDL can be readily oxidized by free radical and not interact with LDL receptor. Lipoprotein pariticles are consisted of lipid andprotein, and fatty acids of lipoproteins are prone to oxidation. LDL particles readily undergo oxidative modification by copper. From the results, oxidized LDL altered its biological properties. A marked increase in the electrophoretic mobility of LDl on agarose gel indicated that negative surface charge of the LDL particles was increased. Also, the results from the HPLC showed that oxidized LDL was degraded into several polypeptides nonenzymatically. Degradation tests which measured the amount of 5-IAF labelled oxidized LDL were carried out by monocyte and hepatocyte cell culture. Hepatocyte cell culture of modified LDL did not show consistent pattern. However, binding rate of modified LDL with HMDM(human monocyte derived macrophage) was enhanced with oxidation, but was retarded by addition of antioxidants(hyaluronic acid, vitamin A, vitamin E). Also comparisons of oxidized-LDL, acetyl-LDL and MDA-LDL showed significant differences in the chemical properteis and binding affinity to HMDM. Thus, modificaition of normal LDL altered its biological properties.

Keywords

References

  1. J. Clin. Invest. v.88 Role of oxidized LDL in atherosclerosis. Wiztum,J.L.;Steninberg,D.
  2. J. Korean. Soc. Food. Nutr. v.23 Fatty acid composition and functional properties of low density lipoprotein and oxdized LDL from human plasma Choi,J.H.;Son,H.S.;Kim,T.W.
  3. Chem. Res. Toxicol. v.3 Biochemical,structural and functional properties of oxized LDL. Esterbauger,H.;Wang,G.;Jurgens,G.
  4. J. Clin. Invest. v.94 Pathophysiological concentration of glucose promote oxidative modification of LDL by a superoxide-dependent pathway. Kawamura,M.;Heineke,J.W.;Chait,A.
  5. Am. J. Clin. Nutr. v.53 Oxidation of lipoproteins and atherosclerosis. Luc,G.;Fruchart,J.C.
  6. Biochem. Biophys. Res. Commun. v.176 Oxidation of cholesterol moiety of LDL in the presence of human endothelial cells or Ca2+. Bhadra,S.;Arshda,M.A.Q.;Rymaszewski,Z.;Norman,E.;Wherley,R;Subbiah,M.T.R.
  7. Biochem. J. v.278 Treatment of macrophages with ox-LDL. Darley-Usmar,V.M.;Seven,A.;Oleary,V.J.;Rogers,M.
  8. J. Lipid Res. v.28 Nonenzymatic oxidative clevage of peptide bonds in approtein B-100 Fong,L.G.;Parthasarathy,S.;Witztum,J.L.;Steinberg,D.
  9. J. Clin. Invest. v.74 Iron and copper promote modification of low density lipoprotein by human ariterial smooth musicle cell in culture. Heinecke,J.W.;Rosen,H.;Chait,A.
  10. Proc. Natl. Acad. Sci. USA. v.187 SH and disulfide linkage of apo B-100 of LDL. Yang,C.Y.;Kim,T.W.;Weng,S.A.;Lee,B.;Yang,M.;Gotto,A.M.;
  11. Biochim. Biophy. Acta. v.1037 Determination of cysteine of apo B-100 of human LDL. Coleman,R.D.;Kim,T.W.;Gotto,A.M.;Yang,C.Y.
  12. Biochim. Biophy. Acta. v.1125 Salmon,S.;Maziere,C.;Malondialdehyde modification and copper-induced autooxidation of HDL decrease cholesterol efflux from human cultured fibroblast,
  13. Atherosclerosis. v.1086 B-carotene inhibits the oxidative modification of LDL. Jialal,I.Norkus,E.P.;Grundy,S.M.
  14. Biochim. Biophys. Acta. v.1044 HDL inhibits the oxdative modification of low density lipoprotein. Parthasarathy,S.;Barnette,J.;Fong,L.G.
  15. Proc. Natl. Acad. Sci. v.81 Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Steinbrecher,U.P.;Parthasarathy,S.;Leake,D.S.;Wiztum,L.G.;Steinberg,D.
  16. Lipids Atherogenesis. v.1 Antioxidants and atherosclerosis Superoki,H.R.