Heterogeneous lipoprotein (a) size isoforms differ by their interaction with the low density lipoprotein receptor and the low density lipoprotein receptor‐related protein/α2‐macroglobulin receptor

FEBS Letters

Groß, Werner³  Mondorf, Uli¹  Hüttinger, Manfred²  Scharnagl, Hubert³  Siekmeier, Rüdiger¹  Beckmann, Angela¹  Preissner, Klaus T.⁵  März, Winfried³  Held, Irmtraud²  Schneider, Wolfgang¹  Curtiss, Linda K.⁴ 

[1]Center of Internal Medicine, Johann Wolfgang Goethe-University, Frankfurt, Germany,

[2]Department of Medical Chemistry, University of Vienna, Austria

[3]Gustav Embden-Center of Biological Chemistry Johann Wolfgang Goethe-University, Frankfurt, Germany

[4]The Scripps Research Institute, Department of Immunology, La Jolla, CA, USA

[5]Haemostasis Research Unit, Kerckhoff-Klinik, Bad Nauheim, Germany

关键词: Lipoprotein (a);    Apolipoprotein B;    Low density lipoprotein receptor related protein;    Plasminogen;    α2-Macroglobulin;    Tissue type plasminogen activator;    Human skin fibroblast;    apo;    apolipoprotein;    α2M;    α2-macroglobulin;    EDTA;    ethylenediaminetetraacetate;    GPC;    gel permeation chromatography;    Lp(a);    lipoprotein (a);    M r;    relative molecular mass;    HMr-Lp(a);    high molecular mass Lp(a);    LMr-Lp(a);    low molecular mass Lp(a);    LRP;    low density lipoprotein receptor-related proteinα2-macroglobulin receptor;    tPA;    tissue-type plasminogen activator;    VLDL;    LDL;    HDL;    very low;    low and high density lipoproteins;    respectively;   

DOI  :  10.1016/0014-5793(93)81087-G

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Lipoprotein (a) (Lp(a)) is a complex of low density lipoprotein (LDL) with apolipoprotein (apo) (a). To examine the size distribution of L_p(a), plasma was separated by fast flow gel filtration and L_p(a): B complexes were determined in the eluate by enzyme immunoassays, in which detection was performed with monoclonal antibodies specific for apoB Lp(a): B particles displayed apparent molecular masses (M_r ) of 2 × 10⁶ to at least 10 × 10⁶. Lp(a) size isoforms differed by the expression of apoB epitopes and their interaction with cultured human skin fibroblasts. LDL was more effective in inhibiting binding, uptake, and degradation of low M_r , Lp(a) than of high M_r Lp(a). In contrast, Glu-plasmmogen, α₂-macroglobulin and tissue-type plasminogen activator were more effective in competing for the cellular degradation of high M_r Lp(a) than of low M_r Lp(a). Ligand blotting revealed that Lp(a) bound to the low density lipoprotein receptor, the low density lipoprotein receptor-related protein/α₂-macroglobulin receptor (LRP) and to two other endosomal membrane proteins. We propose that the LDL receptor preferentially internalizes low M_r Lp(a), whereas LRP may have a role in the clearance of high M_r Lp(a).

【 授权许可】

Unknown