Platelet Activation by the apoB/E Receptor-binding Domain of LDL

I. A. M. Relou; G. Gorter; J. M. H. van Rijn; N. J.-W. Akkerman

doi:10.1055/s-0037-1613100

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2002; 87(05): 880-887
DOI: 10.1055/s-0037-1613100

Review Article

Schattauer GmbH

Platelet Activation by the apoB/E Receptor-binding Domain of LDL

Authors

I. A. M. Relou

¹Laboratory for Thrombosis and Haemostasis, Department of Haematology, University of Utrecht, The Netherlands
G. Gorter

¹Laboratory for Thrombosis and Haemostasis, Department of Haematology, University of Utrecht, The Netherlands
J. M. H. van Rijn

²Department of Clinical Chemistry, University Medical Center Utrecht, and Institute for Biomembranes, University of Utrecht, The Netherlands
N. J.-W. Akkerman

¹Laboratory for Thrombosis and Haemostasis, Department of Haematology, University of Utrecht, The Netherlands

Abstract

Summary

Low density lipoprotein (LDL) increases the sensitivity of human platelets for agonists by activating p38^MAPK. Antibody 4G3 disturbs apoB100 binding to the classical apoB/E receptor and inhibits LDLinduced p38^MAPK activation, whereas an antibody against a distal domain on apoB100 has no effect. Peptide RLTRKRGLKLA mimics the binding domain of apoB100 called the B-site and activates platelet p38^MAPK. Activation by B-site peptide is dose-dependent, transient and followed by desensitization, in accordance with receptor-mediated signalling. A scrambled peptide and a partially homologous peptide RKLRKRLLRDA mimicking the apoB/E receptor binding site of apoE in high density lipoprotein (HDL) also activate p38^MAPK albeit 40% weaker, but an uncharged peptide lacks p38^MAPK activating capacity. LDL and B-site peptide bind to the same binding sites and initiate similar signalling to p38^MAPK and cytosolic phospholipase A2. Thus, LDL and to a lesser extent HDL activate platelets via specific domains in the protein moiety that recognize receptors of the LDL receptor family.

Keywords

LDL - platelets - p38^MAPK - apoB100 - apoE

Volltext

Referenzen

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