Skip to main content
NCBI home page
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
. 1995 Mar 28;92(7):2509–2513. doi: 10.1073/pnas.92.7.2509

Core lipid structure is a major determinant of the oxidative resistance of low density lipoprotein.

B Schuster 1, R Prassl 1, F Nigon 1, M J Chapman 1, P Laggner 1
PMCID: PMC42247  PMID: 7708675

Abstract

The influence of thermally induced changes in the lipid core structure on the oxidative resistance of discrete, homogeneous low density lipoprotein (LDL) subspecies (d, 1.0297-1.0327 and 1.0327-1.0358 g/ml) has been evaluated. The thermotropic transition of the LDL lipid core at temperatures between 15 degrees C and 37 degrees C, determined by differential scanning calorimetry, exerted significant effects on the kinetics of copper-mediated LDL oxidation expressed in terms of intrinsic antioxidant efficiency (lag time) and diene production rate. Thus, the temperature coefficients of oxidative resistance and maximum oxidation rate showed break points at the core transition temperature. Temperature-induced changes in copper binding were excluded as the molecular basis of such effects, as the saturation of LDL with copper was identical below and above the core transition. At temperatures below the transition, the elevation in lag time indicated a greater resistance to oxidation, reflecting a higher degree of antioxidant protection. This effect can be explained by higher motional constraints and local antioxidant concentrations, the latter resulting from the freezing out of antioxidants from crystalline domains of cholesteryl esters and triglycerides. Below the transition temperature, the conjugated diene production rate was decreased, a finding that correlated positively with the average size of the cooperative units of neutral lipids estimated from the calorimetric transition width. The reduced accessibility and structural hindrance in the cluster organization of the core lipids therefore inhibits peroxidation. Our findings provide evidence for a distinct effect of the dynamic state of the core lipids on the oxidative susceptibility of LDL and are therefore relevant to the atherogenicity of these cholesterol-rich particles.

Full text

PDF
2509

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Burks C., Engelman D. M. Cholesteryl myristate conformation in liquid crystalline mesophases determined by neutron scattering. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6863–6867. doi: 10.1073/pnas.78.11.6863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Burton G. W., Ingold K. U. beta-Carotene: an unusual type of lipid antioxidant. Science. 1984 May 11;224(4649):569–573. doi: 10.1126/science.6710156. [DOI] [PubMed] [Google Scholar]
  3. Chapman M. J., Laplaud P. M., Luc G., Forgez P., Bruckert E., Goulinet S., Lagrange D. Further resolution of the low density lipoprotein spectrum in normal human plasma: physicochemical characteristics of discrete subspecies separated by density gradient ultracentrifugation. J Lipid Res. 1988 Apr;29(4):442–458. [PubMed] [Google Scholar]
  4. Deckelbaum R. J., Shipley G. G., Small D. M. Structure and interactions of lipids in human plasma low density lipoproteins. J Biol Chem. 1977 Jan 25;252(2):744–754. [PubMed] [Google Scholar]
  5. Dejager S., Bruckert E., Chapman M. J. Dense low density lipoprotein subspecies with diminished oxidative resistance predominate in combined hyperlipidemia. J Lipid Res. 1993 Feb;34(2):295–308. [PubMed] [Google Scholar]
  6. Di Mascio P., Kaiser S., Sies H. Lycopene as the most efficient biological carotenoid singlet oxygen quencher. Arch Biochem Biophys. 1989 Nov 1;274(2):532–538. doi: 10.1016/0003-9861(89)90467-0. [DOI] [PubMed] [Google Scholar]
  7. Esterbauer H., Striegl G., Puhl H., Rotheneder M. Continuous monitoring of in vitro oxidation of human low density lipoprotein. Free Radic Res Commun. 1989;6(1):67–75. doi: 10.3109/10715768909073429. [DOI] [PubMed] [Google Scholar]
  8. Gieseg S. P., Esterbauer H. Low density lipoprotein is saturable by pro-oxidant copper. FEBS Lett. 1994 May 2;343(3):188–194. doi: 10.1016/0014-5793(94)80553-9. [DOI] [PubMed] [Google Scholar]
  9. Halliwell B. How to characterize a biological antioxidant. Free Radic Res Commun. 1990;9(1):1–32. doi: 10.3109/10715769009148569. [DOI] [PubMed] [Google Scholar]
  10. Kalyanaraman B., Joseph J., Parthasarathy S. Site-specific trapping of reactive species in low-density lipoprotein oxidation: biological implications. Biochim Biophys Acta. 1993 Jun 12;1168(2):220–227. doi: 10.1016/0005-2760(93)90128-v. [DOI] [PubMed] [Google Scholar]
  11. Kleinveld H. A., Hak-Lemmers H. L., Stalenhoef A. F., Demacker P. N. Improved measurement of low-density-lipoprotein susceptibility to copper-induced oxidation: application of a short procedure for isolating low-density lipoprotein. Clin Chem. 1992 Oct;38(10):2066–2072. [PubMed] [Google Scholar]
  12. Kritharides L., Jessup W., Gifford J., Dean R. T. A method for defining the stages of low-density lipoprotein oxidation by the separation of cholesterol- and cholesteryl ester-oxidation products using HPLC. Anal Biochem. 1993 Aug 15;213(1):79–89. doi: 10.1006/abio.1993.1389. [DOI] [PubMed] [Google Scholar]
  13. Kuzuya M., Yamada K., Hayashi T., Funaki C., Naito M., Asai K., Kuzuya F. Role of lipoprotein-copper complex in copper catalyzed-peroxidation of low-density lipoprotein. Biochim Biophys Acta. 1992 Feb 12;1123(3):334–341. doi: 10.1016/0005-2760(92)90015-n. [DOI] [PubMed] [Google Scholar]
  14. Laggner P., Kostner G. M., Degovics G., Worcester D. L. Structure of the cholesteryl ester core of human plasma low density lipoproteins: selective deuteration and neutron small-angle scattering. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4389–4393. doi: 10.1073/pnas.81.14.4389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Laggner P., Kostner G. M. Thermotropic changes in the surface structure of lipoprotein B from human-plasma low-density lipoproteins. A spin-label study. Eur J Biochem. 1978 Mar;84(1):227–232. doi: 10.1111/j.1432-1033.1978.tb12160.x. [DOI] [PubMed] [Google Scholar]
  16. Nigon F., Lesnik P., Rouis M., Chapman M. J. Discrete subspecies of human low density lipoproteins are heterogeneous in their interaction with the cellular LDL receptor. J Lipid Res. 1991 Nov;32(11):1741–1753. [PubMed] [Google Scholar]
  17. Noguchi N., Gotoh N., Niki E. Dynamics of the oxidation of low density lipoprotein induced by free radicals. Biochim Biophys Acta. 1993 Jul 1;1168(3):348–357. [PubMed] [Google Scholar]
  18. Presti F. T., Chan S. I. Cholesterol-phospholipid interaction in membranes. 1. Cholestane spin-label studies of phase behavior of cholesterol-phospholipid liposomes. Biochemistry. 1982 Aug 3;21(16):3821–3830. doi: 10.1021/bi00259a016. [DOI] [PubMed] [Google Scholar]
  19. Reisinger R. E., Atkinson D. Phospholipid/cholesteryl ester microemulsions containing unesterified cholesterol: model systems for low density lipoproteins. J Lipid Res. 1990 May;31(5):849–858. [PubMed] [Google Scholar]
  20. Sattler W., Kostner G. M., Waeg G., Esterbauer H. Oxidation of lipoprotein Lp(a). A comparison with low-density lipoproteins. Biochim Biophys Acta. 1991 Jan 4;1081(1):65–74. doi: 10.1016/0005-2760(91)90251-c. [DOI] [PubMed] [Google Scholar]
  21. Slyper A. H. Low-density lipoprotein density and atherosclerosis. Unraveling the connection. JAMA. 1994 Jul 27;272(4):305–308. [PubMed] [Google Scholar]
  22. 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]
  23. Subczynski W. K., Hyde J. S., Kusumi A. Oxygen permeability of phosphatidylcholine--cholesterol membranes. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4474–4478. doi: 10.1073/pnas.86.12.4474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Tribble D. L., Holl L. G., Wood P. D., Krauss R. M. Variations in oxidative susceptibility among six low density lipoprotein subfractions of differing density and particle size. Atherosclerosis. 1992 Apr;93(3):189–199. doi: 10.1016/0021-9150(92)90255-f. [DOI] [PubMed] [Google Scholar]
  25. de Graaf J., Hak-Lemmers H. L., Hectors M. P., Demacker P. N., Hendriks J. C., Stalenhoef A. F. Enhanced susceptibility to in vitro oxidation of the dense low density lipoprotein subfraction in healthy subjects. Arterioscler Thromb. 1991 Mar-Apr;11(2):298–306. doi: 10.1161/01.atv.11.2.298. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES