Enhanced binding of phospholipase-A2-modified low density lipoprotein by human adipocytes.
Recognition of low density lipoprotein (LDL) by human adipocytes is not dependent on the classical LDL (apoprotein B-E) receptor. To assess whether LDL phospholipids have a role in adipocyte-LDL interactions, binding studies were carried out with human LDL modified with cobra venom phospholipase A2 (PLA2) and freshly isolated adipocytes and purified adipocyte plasma membranes prepared from surgical biopsies. LDL incubated with PLA2 showed increased monoacylphospholipid content, decreased diacylphospholipid content, and increased anodic migration on agarose gel electrophoresis. LDL cholesterol, triglyceride, and protein content remained unchanged. Typically, modification of 16 and 47% of LDL phospholipids enhanced specific binding of 125I-labelled LDL to plasma membranes progressively from 3.1 micrograms LDL bound/mg membrane protein (control) to 5.8 and 28.2 micrograms LDL bound/mg membrane protein, respectively. Nonspecific binding was not altered significantly. Excess unlabelled native LDL and high density lipoprotein (HDL3) effectively inhibited binding of PLA2-modified LDL. Freshly isolated adipocytes also showed enhanced binding and uptake of PLA2-modified LDL (0.1 vs. 0.9 micrograms LDL/10(6) cells x 2 h), control vs. modified). The results demonstrate that alterations of LDL phospholipids significantly enhance LDL binding and suggest a regulatory role for phospholipids in lipoprotein-cell interaction. Furthermore, the results support the view that human adipose tissue may be involved in the metabolism of modified lipoproteins, in vivo.
Natarajan
M K
MK
Institute of Medical Science, University of Toronto, Ont., Canada.
Fong
B S
BS
Angel
A
A
D000273:Adipose Tissue / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism*; D008239:Lysine / Q000502:physiology; D010741:Phospholipases A; D054467:Phospholipases A2; D010743:Phospholipids / Q000502:physiology; D013329:Structure-Activity Relationship
D008077:Lipoproteins, LDL; D010743:Phospholipids; D010741:Phospholipases A; D054467:Phospholipases A2; D008239:Lysine