Isolation, characterization, and uptake in human fibroblasts of an apo(a)-free lipoprotein obtained on reduction of lipoprotein(a)

J Lipid Res. 1985 Nov;26(11):1314-23.


Treatment of native human Lp(a) under nondenaturing conditions with dithiothreitol yielded both a lipoprotein particle and a lipid-free protein component that could be separated by either ultracentrifugation at d 1.063 g/ml or heparin-Sepharose chromatography. The protein component only showed antigenicity against anti-Lp(a) but not against anti-B. It was heterogeneous according to SDS polyacrylamide gel electrophoresis (PAGE) consisting of two bands, a major band with molecular weight similar to apoB and a minor band with slightly lower molecular weight. The lipoprotein particle was similar to LDL with regard to its electrophoretic mobility, lipid-protein composition, its apparent molecular weight according to gel-exclusion chromatography, and its apoprotein content; only apoB was found to be present by SDS-PAGE and immunochemical analysis. This lipoprotein also proved to be identical to LDL in its uptake by the receptor-mediated LDL-pathway in cultured human fibroblasts as shown by the similarity of the concentration-dependent binding, internalization, and degradation curves at 37 degrees C of the 125I-labeled lipoproteins. Normal Lp(a) was not taken up as readily as either its reduced lipoprotein component or LDL in the various steps of the receptor-mediated pathway. The maximal capacity for Lp(a) in the degradation assay was only 25% of that of LDL and it had a fourfold higher Km. It is therefore probable that the LDL-receptor-mediated pathway is not a major route for the clearance of Lp(a) in vivo. These studies suggest that Lp(a) is, in essence, an LDL-particle to which the protein (a) is attached through disulfide bonds to apoB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatography, Affinity
  • Chromatography, Gel
  • Chromatography, High Pressure Liquid
  • Dithiothreitol / pharmacology
  • Electrophoresis, Agar Gel
  • Fibroblasts / metabolism*
  • Humans
  • Immunodiffusion
  • Immunoelectrophoresis
  • Lipids / analysis
  • Lipoprotein(a)
  • Lipoproteins / isolation & purification*
  • Lipoproteins / metabolism
  • Lipoproteins, LDL / metabolism
  • Proteins / analysis
  • Receptors, Cell Surface / metabolism
  • Receptors, Lipoprotein


  • Lipids
  • Lipoprotein(a)
  • Lipoproteins
  • Lipoproteins, LDL
  • Proteins
  • Receptors, Cell Surface
  • Receptors, Lipoprotein
  • Dithiothreitol