Apolipoprotein J (clusterin) induces cholesterol export from macrophage-foam cells: a potential anti-atherogenic function?

Biochem J. 1998 Apr 1;331 ( Pt 1)(Pt 1):231-7. doi: 10.1042/bj3310231.

Abstract

Apolipoprotein J (apo J) is a secreted glycoprotein of which the exact function remains a matter for speculation. Apo J has been implicated in such diverse processes as sperm maturation, regulation of complement activation, programmed cell death, tissue remodelling and lipid transport. In this study a possible role for apo J in lipid transport was explored. Mouse peritoneal macrophages were incubated with acetylated low-density lipoprotein (AcLDL) to produce foam cells containing cholesterol and cholesteryl esters. Incubation of the foam cells with physiological concentrations of purified apo J led to a dose-dependent export of cholesterol. The appearance of cholesterol in the medium was associated predominantly with a decline in intracellular cholesteryl esters rather than intracellular free cholesterol. The kinetics of cholesterol release to apo J were similar to apo A-I, an established promoter of cholesterol efflux. Apo J was also shown to induce phospholipid efflux from cells, whereas the cholesterol exported to the medium was associated with the apo J. Studies using foam cells from apo E-null mice showed that the cholesterol exported to the medium was independent of apo E production by the cells. These results present the first evidence that apo J can promote cholesterol efflux from foam cells and indicates that it might have a function in cellular cholesterol homoeostasis in both normal and pathological situations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arteriosclerosis / metabolism*
  • Arteriosclerosis / prevention & control
  • Biological Transport / drug effects
  • Cells, Cultured
  • Cholesterol / metabolism*
  • Clusterin
  • Dose-Response Relationship, Drug
  • Foam Cells / metabolism*
  • Glycoproteins / pharmacology*
  • Humans
  • Macrophages, Peritoneal / metabolism
  • Macrophages, Peritoneal / pathology
  • Mice
  • Molecular Chaperones*

Substances

  • CLU protein, human
  • Clu protein, mouse
  • Clusterin
  • Glycoproteins
  • Molecular Chaperones
  • Cholesterol