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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Aug 1;89(15):6993–6997. doi: 10.1073/pnas.89.15.6993

Binding of transition metals by apolipoprotein A-I-containing plasma lipoproteins: inhibition of oxidation of low density lipoproteins.

S T Kunitake 1, M R Jarvis 1, R L Hamilton 1, J P Kane 1
PMCID: PMC49631  PMID: 1495991

Abstract

We have found transition metals tightly bound to apolipoprotein A-I-containing lipoproteins [Lp(A-I)] isolated by selected affinity immunosorption from human serum. Prominent among the metal ions detected were iron and copper. By immunoblotting the proteins of Lp(A-I), we detected both transferrin and ceruloplasmin. The transferrin-containing Lp(A-I) particles, isolated by selected affinity immunosorption against transferrin, were larger (mean diameter of 14.2 nm) and had a higher protein content than most high density lipoproteins (HDL). Ultracentrifugally isolated HDL were found to contain much less transferrin, whereas transferrin was found associated with apolipoprotein A-I from the greater than 1.21-g/ml ultracentrifugal fraction. This suggests that the complex is not recovered in the classic HDL density interval because of its very high density. HDL inhibit copper-catalyzed oxidation of low density lipoproteins (LDL) in vitro. We have found that immunoisolated Lp(A-I) are an order of magnitude more effective in inhibiting the oxidation of LDL than ultracentrifugally isolated HDL, on the basis of protein mass. When the Lp(A-I) particles containing transferrin and ceruloplasmin were removed from the bulk of Lp(A-I), inhibition of the in vitro oxidation of LDL was significantly decreased.

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Selected References

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  1. Anderson D. W., Nichols A. V., Forte T. M., Lindgren F. T. Particle distribution of human serum high density lipoproteins. Biochim Biophys Acta. 1977 Jul 22;493(1):55–68. doi: 10.1016/0005-2795(77)90259-8. [DOI] [PubMed] [Google Scholar]
  2. Blanche P. J., Gong E. L., Forte T. M., Nichols A. V. Characterization of human high-density lipoproteins by gradient gel electrophoresis. Biochim Biophys Acta. 1981 Sep 24;665(3):408–419. doi: 10.1016/0005-2760(81)90253-8. [DOI] [PubMed] [Google Scholar]
  3. Bucolo G., David H. Quantitative determination of serum triglycerides by the use of enzymes. Clin Chem. 1973 May;19(5):476–482. [PubMed] [Google Scholar]
  4. Carson S. D. Plasma high density lipoproteins inhibit the activation of coagulation factor X by factor VIIa and tissue factor. FEBS Lett. 1981 Sep 14;132(1):37–40. doi: 10.1016/0014-5793(81)80422-x. [DOI] [PubMed] [Google Scholar]
  5. Chen G. C., Kane J. P., Hamilton R. L. Thermal behavior of cores of human serum triglyceride-rich lipoproteins: a study of induced circular dichroism of beta-carotene. Biochemistry. 1984 Mar 13;23(6):1119–1124. doi: 10.1021/bi00301a013. [DOI] [PubMed] [Google Scholar]
  6. Chen G. C., Zhu S., Hardman D. A., Schilling J. W., Lau K., Kane J. P. Structural domains of human apolipoprotein B-100. Differential accessibility to limited proteolysis of B-100 in low density and very low density lipoproteins. J Biol Chem. 1989 Aug 25;264(24):14369–14375. [PubMed] [Google Scholar]
  7. Chen Y. D., Kraemer F. B., Reaven G. M. Identification of specific high density lipoprotein-binding sites in rat testis and regulation of binding by human chorionic gonadotropin. J Biol Chem. 1980 Oct 10;255(19):9162–9167. [PubMed] [Google Scholar]
  8. Cheung M. C., Albers J. J. Characterization of lipoprotein particles isolated by immunoaffinity chromatography. Particles containing A-I and A-II and particles containing A-I but no A-II. J Biol Chem. 1984 Oct 10;259(19):12201–12209. [PubMed] [Google Scholar]
  9. Cheung M. C., Wolf A. C., Lum K. D., Tollefson J. H., Albers J. J. Distribution and localization of lecithin:cholesterol acyltransferase and cholesteryl ester transfer activity in A-I-containing lipoproteins. J Lipid Res. 1986 Nov;27(11):1135–1144. [PubMed] [Google Scholar]
  10. Chung B. H., Segrest J. P., Cone J. T., Pfau J., Geer J. C., Duncan L. A. High resolution plasma lipoprotein cholesterol profiles by a rapid, high volume semi-automated method. J Lipid Res. 1981 Aug;22(6):1003–1014. [PubMed] [Google Scholar]
  11. Curry M. D., Alaupovic P., Suenram C. A. Determination of apolipoprotein A and its constitutive A-I and A-II polypeptides by separate electroimmunoassays. Clin Chem. 1976 Mar;22(3):315–322. [PubMed] [Google Scholar]
  12. Fainaru M., Havel R. J., Felker T. E. Radioimmunoassay of apolipoprotein A-I of rat serum. Biochim Biophys Acta. 1976 Sep 28;446(1):56–68. doi: 10.1016/0005-2795(76)90097-0. [DOI] [PubMed] [Google Scholar]
  13. Fielding C. J., Fielding P. E. Cholesterol transport between cells and body fluids. Role of plasma lipoproteins and the plasma cholesterol esterification system. Med Clin North Am. 1982 Mar;66(2):363–373. doi: 10.1016/s0025-7125(16)31425-0. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Habeeb A. F. Determination of free amino groups in proteins by trinitrobenzenesulfonic acid. Anal Biochem. 1966 Mar;14(3):328–336. doi: 10.1016/0003-2697(66)90275-2. [DOI] [PubMed] [Google Scholar]
  16. Huang H., Kauan J. W., Guilbault G. G. Fluorometric enzymatic determination of total cholesterol in serum. Clin Chem. 1975 Oct;21(11):1605–1608. [PubMed] [Google Scholar]
  17. Ivanova E. M., Nikiforova A. A., Alksnis E. G. Poluchenie proteoliposom--iskusstvennogo substrata dlia izmereniia skorosti letsitin-kholesterin-atsiltransferaznoi reaktsii v tsel'noi plazme krovi. Vopr Med Khim. 1985 Nov-Dec;31(6):123–126. [PubMed] [Google Scholar]
  18. James R. W., Hochstrasser D., Tissot J. D., Funk M., Appel R., Barja F., Pellegrini C., Muller A. F., Pometta D. Protein heterogeneity of lipoprotein particles containing apolipoprotein A-I without apolipoprotein A-II and apolipoprotein A-I with apolipoprotein A-II isolated from human plasma. J Lipid Res. 1988 Dec;29(12):1557–1571. [PubMed] [Google Scholar]
  19. Kane J. P., Hardman D. A., Dimpfl J. C., Levy J. A. Apolipoprotein is responsible for neutralization of xenotropic type C virus by mouse serum. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5957–5961. doi: 10.1073/pnas.76.11.5957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Klimov A. N., Kozhemiakin L. A., Pleskov V. M., Andreeva L. I. Antioksidantnyi éffekt lipoproteidov vysokoi plotnosti pri perekisnom okislenii lipoproteidov nizkoi plotnosti. Biull Eksp Biol Med. 1987 May;103(5):550–552. [PubMed] [Google Scholar]
  21. Kostner G. M., Patsch J. R., Sailer S., Braunsteiner H., Holasek A. Polypeptide distribution of the main lipoprotein density classes separated from human plasma by rate zonal ultracentrifugation. Eur J Biochem. 1974 Jun 15;45(2):611–621. doi: 10.1111/j.1432-1033.1974.tb03587.x. [DOI] [PubMed] [Google Scholar]
  22. Kunitake S. T., Chen G. C., Kung S. F., Schilling J. W., Hardman D. A., Kane J. P. Pre-beta high density lipoprotein. Unique disposition of apolipoprotein A-I increases susceptibility to proteolysis. Arteriosclerosis. 1990 Jan-Feb;10(1):25–30. doi: 10.1161/01.atv.10.1.25. [DOI] [PubMed] [Google Scholar]
  23. Kunitake S. T., Kane J. P. Factors affecting the integrity of high density lipoproteins in the ultracentrifuge. J Lipid Res. 1982 Aug;23(6):936–940. [PubMed] [Google Scholar]
  24. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  25. Lagrost L., Gambert P., Boquillon M., Lallemant C. Evidence for high density lipoproteins as the major apolipoprotein A-IV-containing fraction in normal human serum. J Lipid Res. 1989 Oct;30(10):1525–1534. [PubMed] [Google Scholar]
  26. Mahley R. W., Holcombe K. S. Alterations of the plasma lipoproteins and apoproteins following cholesterol feeding in the rat. J Lipid Res. 1977 May;18(3):314–324. [PubMed] [Google Scholar]
  27. Makino T., Takahara K. Direct determination of plasma copper and zinc in infants by atomic absorption with discrete nebulization. Clin Chem. 1981 Aug;27(8):1445–1447. [PubMed] [Google Scholar]
  28. Marcel Y. L., Weech P. K., Nguyen T. D., Milne R. W., McConathy W. J. Apolipoproteins as the basis for heterogeneity in high-density lipoprotein2 and high-density lipoprotein3. Studies by isoelectric focusing on agarose films. Eur J Biochem. 1984 Sep 17;143(3):467–476. doi: 10.1111/j.1432-1033.1984.tb08394.x. [DOI] [PubMed] [Google Scholar]
  29. McNamara B. C., Booth R., Stansfield D. A. Evidence for an essential role for high-density lipoprotein in progesterone synthesis by rat corpus luteum. FEBS Lett. 1981 Nov 2;134(1):79–82. doi: 10.1016/0014-5793(81)80555-8. [DOI] [PubMed] [Google Scholar]
  30. McVicar J. P., Kunitake S. T., Hamilton R. L., Kane J. P. Characteristics of human lipoproteins isolated by selected-affinity immunosorption of apolipoprotein A-I. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1356–1360. doi: 10.1073/pnas.81.5.1356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Ohashi M., Carr B. R., Simpson E. R. Binding of high density lipoprotein to human fetal adrenal membrane fractions. Endocrinology. 1981 Sep;109(3):783–788. doi: 10.1210/endo-109-3-783. [DOI] [PubMed] [Google Scholar]
  32. Ohta T., Takata K., Horiuchi S., Morino Y., Matsuda I. Protective effect of lipoproteins containing apoprotein A-I on Cu2+-catalyzed oxidation of human low density lipoprotein. FEBS Lett. 1989 Nov 6;257(2):435–438. doi: 10.1016/0014-5793(89)81590-x. [DOI] [PubMed] [Google Scholar]
  33. Ormerod W. E., Venkatesan S. Similarities of lipid metabolism in mammalian and protozoan cells: an evolutionary hypothesis for the prevalence of atheroma. Microbiol Rev. 1982 Sep;46(3):296–307. doi: 10.1128/mr.46.3.296-307.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Parthasarathy S., Barnett J., Fong L. G. High-density lipoprotein inhibits the oxidative modification of low-density lipoprotein. Biochim Biophys Acta. 1990 May 22;1044(2):275–283. doi: 10.1016/0005-2760(90)90314-n. [DOI] [PubMed] [Google Scholar]
  35. Rudel L. L., Lee J. A., Morris M. D., Felts J. M. Characterization of plasma lipoproteins separated and purified by agarose-column chromatography. Biochem J. 1974 Apr;139(1):89–95. doi: 10.1042/bj1390089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Steinberg D., Parthasarathy S., Carew T. E., Khoo J. C., Witztum J. L. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989 Apr 6;320(14):915–924. doi: 10.1056/NEJM198904063201407. [DOI] [PubMed] [Google Scholar]
  37. Stewart C. P., Hendry E. B. The phospholipins of blood. Biochem J. 1935 Jul;29(7):1683–1689. doi: 10.1042/bj0291683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Tauber J. P., Cheng J., Massoglia S., Gospodarowicz D. High density lipoproteins and the growth of vascular endothelial cells in serum-free medium. In Vitro. 1981 Jun;17(6):519–530. doi: 10.1007/BF02633513. [DOI] [PubMed] [Google Scholar]
  39. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Ulevitch R. J., Johnston A. R., Weinstein D. B. New function for high density lipoproteins. Isolation and characterization of a bacterial lipopolysaccharide-high density lipoprotein complex formed in rabbit plasma. J Clin Invest. 1981 Mar;67(3):827–837. doi: 10.1172/JCI110100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Utermann G. Disc-electrophoretic patterns of human serum high density lipoproteins. Clin Chim Acta. 1972 Feb;36(2):521–529. doi: 10.1016/0009-8981(72)90029-0. [DOI] [PubMed] [Google Scholar]
  42. Yagi K. A simple fluorometric assay for lipoperoxide in blood plasma. Biochem Med. 1976 Apr;15(2):212–216. doi: 10.1016/0006-2944(76)90049-1. [DOI] [PubMed] [Google Scholar]

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