Je. Stewart et al., RECEPTOR-BINDING OF AN APOLIPOPROTEIN E-RICH SUBFRACTION OF HIGH-DENSITY-LIPOPROTEIN TO RAT AND HUMAN BRAIN MEMBRANES, International journal of biochemistry & cell biology, 30(3), 1998, pp. 407-415
During nerve cell degeneration, cholesterol released from the degradin
g cells is conserved through the formation of a cholesterol-apolipopro
tein (apo) E complex which is subsequently taken up by regenerating ne
rve cells. The aim of the present project was to identify the physiolo
gically relevant lipoprotein receptor for this lipoprotein complex whi
ch has remained elusive. HDL was separated into apo E-rich and apo E-p
oor subfractions and labelled with [C-14]-sucrose. Labelled apo E-rich
HDL bound to rat brain membranes in a time-and ligand concentration-d
ependent manner and was a saturable process. Essentially no binding oc
curred with [C-14]-apo E-poor HDL or with free apo E. Binding was part
ially inhibited by low density lipoprotein (LDL) and by alpha(2)-macro
globulin. These results provide new evidence that native apoE-rich HDL
particles resembling those present in the brain bind to rat brain mem
branes and that the binding may be due, at least in part, to the LDL r
eceptor and to the LDL-receptor related protein. Evidence was also pro
vided for the presence of a receptor which binds [C-14]-sucrose human
apoE-rich HDL in human brain. Characterisation of the receptor which m
ediates the uptake of cholesterol from HDL-like complexes by brain cel
ls is important in understanding the role of apoE in the central nervo
us system and of the alterations which occur in disorders such as Alzh
eimer's disease. (C) 1998 Elsevier Science Ltd. All rights reserved.