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Derivatization of Apo-Low-Density Lipoprotein Lysine Residues by Lipid Peroxidation Products during Low-Density Lipoprotein Oxidation

  • Urs Peter Steinbrecher
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)

Abstract

Cultured endothelial cells or arterial smooth muscle cells have previously been shown to promote LDL oxidation. Oxidized LDL is not recognized by the LDL receptor of fibroblasts but is rapidly degraded by macrophages via the “scavenger” receptor pathway. The present studies were done to determine if these changes in receptor recognition might result from derivatization of lysine residues of apo B by products formed during the peroxidation of LDL lipids. Modification of lysine groups was suggested by a decrease of up to 50% in trinitrobenzenesulfonic acid reactivity in oxidized or endothelial cell modified LDL. Amino-acid analysis confirmed that this resulted mainly from loss of lysine. To determine if the change in lysine occurred through derivation by lipid peroxidation products, LDL was labeled with trace amounts of 2-[l-14C]-or 2-[5,6,8,9,11,12,14,15-3H]arachidonylphosphatidylcholine. After oxidation by exposure to 5 μM CuSO4 for 24 hr, the radioactivity bound to protein was significantly greater than that in nonoxidized control LDL or in oxidized LDL labeled with 2-[l-14C]palmitoylphosphatidylcholine. Ultrafiltration revealed that 20-30% of the total label from arachi-donate was released from LDL during oxidation; nearly all of this radioactivity was in material more polar than peroxidized fatty acids. The protein component of oxidized LDL was highly fluorescent, with excitation and emission maxima of 350 and 433 nm, respectively. These results support the hypothesis that LDL oxidation leads to scission of polyunsaturated fatty acids with release of aldehyde products that then form fluorescent adducts with lysine ε-amino groups. This modification of lysines may explain the altered biological properties of oxidized or endothelial-cell-modified LDL.

Keywords

Lipid Peroxidation Product Familial Hypercholesterolemia Arterial Smooth Muscle Cell Peroxidized Fatty Acid Cholesteryl Ester Accumulation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Urs Peter Steinbrecher
    • 1
  1. 1.Division of Gastroenterology, Department of MedicineHealth Sciences Centre HospitalVancouverCanada

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