Effect of apoprotein cross-linking on the metabolism of human HDL3 in rat.
Apo E-free human high-density lipoprotein (HDL3) was labeled with 125I in apoprotein and with 3H in cholesteryl linoleyl ether (a non-hydrolyzable analogue of cholesteryl ester). The labeled HDL3 was modified by cross-linking of apoproteins with dimethylsuberimidate (DMS) to inhibit binding to HDL specific receptors. The control and the DMS HDL3 were characterized with respect to their rate of clearance from rat blood, in vivo binding to major rat organs and in vitro binding to purified rat liver plasma membranes. Both 125I and 3H labels from control HDL3 were cleared from rat blood monoexponentially, but 3H at a faster rate than 125I (3H t1/2 = 3.0-4.1 h; 125I t1/2 = 7.0-7.7 h). This difference is consistent with reports of the nonendocytotic selective uptake of HDL-associated cholesteryl ester. DMS modification did not affect the rate of 3H clearance whereas it increased the rate of 125I clearance (HDL3 t1/2 = 7.7 h; DMS HDL3 t1/2 = 4.1 h). Both in vivo binding to rat organs and in vitro binding to rat liver membranes confirmed that DMS modification inhibited the specific binding of HDL, but also suggested that the modification produced saturable binding of HDL to a separate class of sites. Thus, the present data do not rule out the involvement of direct HDL-cell interaction in the selective uptake of HDL cholesteryl ester. However, results suggest that the binding of HDL to its specific cell surface sites is not necessary for this uptake.
Unité INSERM 286, Faculté de Médecine Xavier-Bichat, Paris, France.
C
C
Senault
F H
FH
Mahlberg
G
G
Renaud
A
A
Girard-Globa
G K
GK
Chacko
D000107:Acetylation; D000818:Animals; D001053:Apolipoproteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D003432:Cross-Linking Reagents; D004120:Dimethyl Suberimidate; D006801:Humans; D066298:In Vitro Techniques; D008075:Lipoproteins, HDL / Q000378:metabolism* / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D001053:Apolipoproteins; D002788:Cholesterol Esters; D003432:Cross-Linking Reagents; D008075:Lipoproteins, HDL; D004120:Dimethyl Suberimidate