Effects of high-density lipoprotein particles containing apo A-I, with or without apo A-II, on intracellular cholesterol efflux

Shinichi Oikawa, Armando J Mendez, John F. Oram, Edwin L. Bierman, Marian C. Cheung

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Previous reports have shown a differential effect of high-density lipoprotein (HDL) particles which contain apolipoprotein (apo) A-I without apo A-II (Lp A-I) and particles containing both apo A-I and apo A-II (Lp A-I/A-II) on cholesterol efflux from the mouse adipocyte cell line Obl771, with Lp A-I and Lp A-I/A-II being active and inactive cholesterol efflux promotors, respectively. The present study was conducted to examine the roles of these two populations of apo-specific HDL particles on reverse cholesterol transport from cholesterol-loaded human skin fibroblasts and bovine aortic endothelial cells. The ability of HDL particles to remove intracellular cholesterol was tested by measuring depletion of the substrate pool for acyl-CoA: cholesterol acyltransferase (ACAT) and efflux of newly synthesized cholesterol, while removal of plasma membrane cholesterol was assessed by measuring efflux of [3H]cholesterol from prelabeled cells. Lp A-I and Lp A-I/A-II isolated from HDL2, HDL3 or plasma by immunoaffinity techniques each decreased esterification of cholesterol by both fibroblasts and endothelial cells. A mixture of Lp A-I and Lp A-I/A-II isolated from HDL3 decreased cholesterol esterification by fibroblasts in an additive manner, thus demonstrating that Lp A-I/A-II did not inhibit Lp A-I-mediated cholesterol efflux. Both Lp A-I and Lp A-I/A-II promoted efflux of sterol newly synthesized by fibroblasts, and no significant differences were observed between the apo-specific particles. Apo-specific particles were also similarly effective at preventing the accumulation of LDL-derived cholesterol in cholesterol-depleted fibroblasts. Efflux of [3H]cholesterol from plasma membranes was stimulated to similar extents by Lp A-I and Lp A-I/A-II isolated from either HDL2, HDL3 or plasma. Thus, the apo-specific HDL particles Lp A-I and Lp A-I/A-II are both effective promoters of cholesterol efflux from fibroblasts and aortic endothelial cells.

Original languageEnglish
Pages (from-to)327-334
Number of pages8
JournalBiochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
Volume1165
Issue number3
DOIs
StatePublished - Jan 10 1993
Externally publishedYes

Fingerprint

Apolipoprotein A-II
Apolipoprotein A-I
HDL Lipoproteins
Cholesterol
Fibroblasts
Apolipoproteins
Endothelial cells
Endothelial Cells
Esterification
Cell membranes
Cell Membrane
Sterol O-Acyltransferase
Plasmas
Sterols
Adipocytes
LDL Cholesterol
HDL Cholesterol

Keywords

  • Apolipoprotein
  • Cell culture
  • High-density lipoprotein
  • Immunoaffinity chromatography
  • Reverse cholesterol transport

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Endocrinology

Cite this

Effects of high-density lipoprotein particles containing apo A-I, with or without apo A-II, on intracellular cholesterol efflux. / Oikawa, Shinichi; Mendez, Armando J; Oram, John F.; Bierman, Edwin L.; Cheung, Marian C.

In: Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism, Vol. 1165, No. 3, 10.01.1993, p. 327-334.

Research output: Contribution to journalArticle

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AU - Mendez, Armando J

AU - Oram, John F.

AU - Bierman, Edwin L.

AU - Cheung, Marian C.

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N2 - Previous reports have shown a differential effect of high-density lipoprotein (HDL) particles which contain apolipoprotein (apo) A-I without apo A-II (Lp A-I) and particles containing both apo A-I and apo A-II (Lp A-I/A-II) on cholesterol efflux from the mouse adipocyte cell line Obl771, with Lp A-I and Lp A-I/A-II being active and inactive cholesterol efflux promotors, respectively. The present study was conducted to examine the roles of these two populations of apo-specific HDL particles on reverse cholesterol transport from cholesterol-loaded human skin fibroblasts and bovine aortic endothelial cells. The ability of HDL particles to remove intracellular cholesterol was tested by measuring depletion of the substrate pool for acyl-CoA: cholesterol acyltransferase (ACAT) and efflux of newly synthesized cholesterol, while removal of plasma membrane cholesterol was assessed by measuring efflux of [3H]cholesterol from prelabeled cells. Lp A-I and Lp A-I/A-II isolated from HDL2, HDL3 or plasma by immunoaffinity techniques each decreased esterification of cholesterol by both fibroblasts and endothelial cells. A mixture of Lp A-I and Lp A-I/A-II isolated from HDL3 decreased cholesterol esterification by fibroblasts in an additive manner, thus demonstrating that Lp A-I/A-II did not inhibit Lp A-I-mediated cholesterol efflux. Both Lp A-I and Lp A-I/A-II promoted efflux of sterol newly synthesized by fibroblasts, and no significant differences were observed between the apo-specific particles. Apo-specific particles were also similarly effective at preventing the accumulation of LDL-derived cholesterol in cholesterol-depleted fibroblasts. Efflux of [3H]cholesterol from plasma membranes was stimulated to similar extents by Lp A-I and Lp A-I/A-II isolated from either HDL2, HDL3 or plasma. Thus, the apo-specific HDL particles Lp A-I and Lp A-I/A-II are both effective promoters of cholesterol efflux from fibroblasts and aortic endothelial cells.

AB - Previous reports have shown a differential effect of high-density lipoprotein (HDL) particles which contain apolipoprotein (apo) A-I without apo A-II (Lp A-I) and particles containing both apo A-I and apo A-II (Lp A-I/A-II) on cholesterol efflux from the mouse adipocyte cell line Obl771, with Lp A-I and Lp A-I/A-II being active and inactive cholesterol efflux promotors, respectively. The present study was conducted to examine the roles of these two populations of apo-specific HDL particles on reverse cholesterol transport from cholesterol-loaded human skin fibroblasts and bovine aortic endothelial cells. The ability of HDL particles to remove intracellular cholesterol was tested by measuring depletion of the substrate pool for acyl-CoA: cholesterol acyltransferase (ACAT) and efflux of newly synthesized cholesterol, while removal of plasma membrane cholesterol was assessed by measuring efflux of [3H]cholesterol from prelabeled cells. Lp A-I and Lp A-I/A-II isolated from HDL2, HDL3 or plasma by immunoaffinity techniques each decreased esterification of cholesterol by both fibroblasts and endothelial cells. A mixture of Lp A-I and Lp A-I/A-II isolated from HDL3 decreased cholesterol esterification by fibroblasts in an additive manner, thus demonstrating that Lp A-I/A-II did not inhibit Lp A-I-mediated cholesterol efflux. Both Lp A-I and Lp A-I/A-II promoted efflux of sterol newly synthesized by fibroblasts, and no significant differences were observed between the apo-specific particles. Apo-specific particles were also similarly effective at preventing the accumulation of LDL-derived cholesterol in cholesterol-depleted fibroblasts. Efflux of [3H]cholesterol from plasma membranes was stimulated to similar extents by Lp A-I and Lp A-I/A-II isolated from either HDL2, HDL3 or plasma. Thus, the apo-specific HDL particles Lp A-I and Lp A-I/A-II are both effective promoters of cholesterol efflux from fibroblasts and aortic endothelial cells.

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KW - Cell culture

KW - High-density lipoprotein

KW - Immunoaffinity chromatography

KW - Reverse cholesterol transport

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