Receptor binding of an apolipoprotein E-rich subfraction of high density lipoprotein to rat and human brain membranes.
During nerve cell degeneration, cholesterol released from the degrading cells is conserved through the formation of a cholesterol-apolipoprotein (apo) E complex which is subsequently taken up by regenerating nerve cells. The aim of the present project was to identify the physiologically relevant lipoprotein receptor for this lipoprotein complex which has remained elusive. HDL was separated into apo E-rich and apo E-poor subfractions and labelled with [14C]-sucrose. Labelled apo E-rich HDL bound to rat brain membranes in a time- and ligand concentration-dependent manner and was a saturable process. Essentially no binding occurred with [14C]-apo E-poor HDL or with free apo E. Binding was partially inhibited by low density lipoprotein (LDL) and by alpha 2-macroglobulin. These results provide new evidence that native apoE-rich HDL particles resembling those present in the brain bind to rat brain membranes and that the binding may be due, at least in part, to the LDL receptor and to the LDL-receptor related protein. Evidence was also provided for the presence of a receptor which binds [14C]-sucrose human apoE-rich HDL in human brain. Characterisation of the receptor which mediates the uptake of cholesterol from HDL-like complexes by brain cells is important in understanding the role of apoE in the central nervous system and of the alterations which occur in disorders such as Alzheimer's disease.
Stewart
J E
JE
Department of Molecular and Cell Biology, Marischal College, University of Aberdeen, UK.
Skinner
E R
ER
Best
P V
PV
D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000032:analysis / Q000378:metabolism*; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008566:Membranes / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology; D016601:RNA-Binding Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D018110:Receptors, Lipoprotein / Q000378:metabolism*
D001057:Apolipoproteins E; D002352:Carrier Proteins; D008075:Lipoproteins, HDL; D016601:RNA-Binding Proteins; D018110:Receptors, Lipoprotein; C031616:high density lipoprotein receptors; C075197:high density lipoprotein binding protein