High density lipoprotein phospholipid composition is a major determinant of the bi-directional flux and net movement of cellular free cholesterol mediated by scavenger receptor BI

J Biol Chem. 2000 Nov 24;275(47):36596-604. doi: 10.1074/jbc.M006924200.

Abstract

The role of high density lipoprotein (HDL) phospholipid in scavenger receptor BI (SR-BI)-mediated free cholesterol flux was examined by manipulating HDL(3) phosphatidylcholine and sphingomyelin content. Both phosphatidylcholine and sphingomyelin enrichment of HDL enhanced the net efflux of cholesterol from SR-BI-expressing COS-7 cells but by two different mechanisms. Phosphatidylcholine enrichment of HDL increased efflux, whereas sphingomyelin enrichment decreased influx of HDL cholesterol. Although similar trends were observed in control (vector-transfected) COS-7 cells, SR-BI overexpression amplified the effects of phosphatidylcholine and sphingomyelin enrichment of HDL 25- and 2.8-fold, respectively. By using both phosphatidylcholine-enriched and phospholipase A(2)-treated HDL to obtain HDL with a graded phosphatidylcholine content, we showed that SR-BI-mediated cholesterol efflux was highly correlated (r(2) = 0.985) with HDL phosphatidylcholine content. The effects of varying HDL phospholipid composition on SR-BI-mediated free cholesterol flux were not correlated with changes in either the K(d) or B(max) values for high affinity binding to SR-BI. We conclude that SR-BI-mediated free cholesterol flux is highly sensitive to HDL phospholipid composition. Thus, factors that regulate cellular SR-BI expression and the local modification of HDL phospholipid composition will have a large impact on reverse cholesterol transport.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD36 Antigens / metabolism*
  • COS Cells
  • Cholesterol / metabolism*
  • Kinetics
  • Lipoproteins, HDL / chemistry*
  • Lipoproteins, HDL / metabolism
  • Lipoproteins, HDL2
  • Lipoproteins, HDL3
  • Membrane Proteins*
  • Phosphatidylcholines / metabolism
  • Phospholipases A / metabolism
  • Phospholipids / chemistry*
  • Receptors, Immunologic*
  • Receptors, Lipoprotein / metabolism*
  • Receptors, Scavenger
  • Scavenger Receptors, Class B
  • Sphingomyelins / metabolism
  • Transfection

Substances

  • CD36 Antigens
  • Lipoproteins, HDL
  • Lipoproteins, HDL2
  • Lipoproteins, HDL3
  • Membrane Proteins
  • Phosphatidylcholines
  • Phospholipids
  • Receptors, Immunologic
  • Receptors, Lipoprotein
  • Receptors, Scavenger
  • Scarb1 protein, mouse
  • Scavenger Receptors, Class B
  • Sphingomyelins
  • Cholesterol
  • Phospholipases A