Cholesterol efflux mediated by apolipoproteins is an active cellular process distinct from efflux mediated by passive diffusion

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

It is becoming increasingly accepted that removal of cellular cholesterol occurs by at least two pathways, one involving the well-described aqueous diffusion mechanism and another promoted by lipid-free apolipoproteins. We compared the contribution of apolipoprotein-dependent and -independent pathways, taking into consideration the influence of cellular metabolism, on cholesterol efflux promoted by different extracellular acceptor types. The acceptors used were assumed to participate in only passive efflux by lipid-dependent mechanisms (phospholipid vesicles and trypsin-modified high density lipoproteins) or to stimulate efflux by apolipoprotein-dependent pathways (purified apolipoprotein A-I and high density lipoproteins). Apolipoprotein-mediated cholesterol efflux was only apparent in growth-arrested or cholesterol-enriched cells and required metabolic energy. In contrast, cholesterol efflux by apolipoprotein-depleted acceptors did not depend on cell growth state, cholesterol enrichment, or metabolic energy. Apolipoprotein-mediated efflux was not observed at temperatures below 22≡C, while apolipoprotein-independent efflux was only reduced by 50% at 4°C compared with incubations at 37°C. Additionally, apolipoproteins promoted a more rapid and larger decrease in intracellular cholesteryl esters when measured by changes in cholesteryl ester radioactivity, mass, or the pool of cholesterol available for esterification by acyl coenzyme A:cholesterol acyltransferase. Efflux of excess cellular cholesterol by an apolipoprotein-dependent pathway appears to involve specific cellular events consistent with the properties of an active transport pathway and distinguishable from cholesterol efflux by apolipoprotein-depleted acceptors through passive mechanisms.

Original languageEnglish
Pages (from-to)1807-1821
Number of pages15
JournalJournal of Lipid Research
Volume38
Issue number9
StatePublished - Sep 1 1997

Fingerprint

Apolipoproteins
Cholesterol
Cholesterol Esters
HDL Lipoproteins
Sterol O-Acyltransferase
Lipids
Acyl Coenzyme A
Active Biological Transport
Esterification
Apolipoprotein A-I
Radioactivity
Cell growth
Growth
Metabolism
Trypsin
Phospholipids
Temperature

Keywords

  • Apolipoprotein A-1
  • Cholesteryl esters
  • Fibroblasts
  • High density lipo-proteins
  • Phospholipid vesicles

ASJC Scopus subject areas

  • Endocrinology

Cite this

@article{28d573d122c34690afe743eab90667b3,
title = "Cholesterol efflux mediated by apolipoproteins is an active cellular process distinct from efflux mediated by passive diffusion",
abstract = "It is becoming increasingly accepted that removal of cellular cholesterol occurs by at least two pathways, one involving the well-described aqueous diffusion mechanism and another promoted by lipid-free apolipoproteins. We compared the contribution of apolipoprotein-dependent and -independent pathways, taking into consideration the influence of cellular metabolism, on cholesterol efflux promoted by different extracellular acceptor types. The acceptors used were assumed to participate in only passive efflux by lipid-dependent mechanisms (phospholipid vesicles and trypsin-modified high density lipoproteins) or to stimulate efflux by apolipoprotein-dependent pathways (purified apolipoprotein A-I and high density lipoproteins). Apolipoprotein-mediated cholesterol efflux was only apparent in growth-arrested or cholesterol-enriched cells and required metabolic energy. In contrast, cholesterol efflux by apolipoprotein-depleted acceptors did not depend on cell growth state, cholesterol enrichment, or metabolic energy. Apolipoprotein-mediated efflux was not observed at temperatures below 22≡C, while apolipoprotein-independent efflux was only reduced by 50{\%} at 4°C compared with incubations at 37°C. Additionally, apolipoproteins promoted a more rapid and larger decrease in intracellular cholesteryl esters when measured by changes in cholesteryl ester radioactivity, mass, or the pool of cholesterol available for esterification by acyl coenzyme A:cholesterol acyltransferase. Efflux of excess cellular cholesterol by an apolipoprotein-dependent pathway appears to involve specific cellular events consistent with the properties of an active transport pathway and distinguishable from cholesterol efflux by apolipoprotein-depleted acceptors through passive mechanisms.",
keywords = "Apolipoprotein A-1, Cholesteryl esters, Fibroblasts, High density lipo-proteins, Phospholipid vesicles",
author = "Mendez, {Armando J}",
year = "1997",
month = "9",
day = "1",
language = "English",
volume = "38",
pages = "1807--1821",
journal = "Journal of Lipid Research",
issn = "0022-2275",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "9",

}

TY - JOUR

T1 - Cholesterol efflux mediated by apolipoproteins is an active cellular process distinct from efflux mediated by passive diffusion

AU - Mendez, Armando J

PY - 1997/9/1

Y1 - 1997/9/1

N2 - It is becoming increasingly accepted that removal of cellular cholesterol occurs by at least two pathways, one involving the well-described aqueous diffusion mechanism and another promoted by lipid-free apolipoproteins. We compared the contribution of apolipoprotein-dependent and -independent pathways, taking into consideration the influence of cellular metabolism, on cholesterol efflux promoted by different extracellular acceptor types. The acceptors used were assumed to participate in only passive efflux by lipid-dependent mechanisms (phospholipid vesicles and trypsin-modified high density lipoproteins) or to stimulate efflux by apolipoprotein-dependent pathways (purified apolipoprotein A-I and high density lipoproteins). Apolipoprotein-mediated cholesterol efflux was only apparent in growth-arrested or cholesterol-enriched cells and required metabolic energy. In contrast, cholesterol efflux by apolipoprotein-depleted acceptors did not depend on cell growth state, cholesterol enrichment, or metabolic energy. Apolipoprotein-mediated efflux was not observed at temperatures below 22≡C, while apolipoprotein-independent efflux was only reduced by 50% at 4°C compared with incubations at 37°C. Additionally, apolipoproteins promoted a more rapid and larger decrease in intracellular cholesteryl esters when measured by changes in cholesteryl ester radioactivity, mass, or the pool of cholesterol available for esterification by acyl coenzyme A:cholesterol acyltransferase. Efflux of excess cellular cholesterol by an apolipoprotein-dependent pathway appears to involve specific cellular events consistent with the properties of an active transport pathway and distinguishable from cholesterol efflux by apolipoprotein-depleted acceptors through passive mechanisms.

AB - It is becoming increasingly accepted that removal of cellular cholesterol occurs by at least two pathways, one involving the well-described aqueous diffusion mechanism and another promoted by lipid-free apolipoproteins. We compared the contribution of apolipoprotein-dependent and -independent pathways, taking into consideration the influence of cellular metabolism, on cholesterol efflux promoted by different extracellular acceptor types. The acceptors used were assumed to participate in only passive efflux by lipid-dependent mechanisms (phospholipid vesicles and trypsin-modified high density lipoproteins) or to stimulate efflux by apolipoprotein-dependent pathways (purified apolipoprotein A-I and high density lipoproteins). Apolipoprotein-mediated cholesterol efflux was only apparent in growth-arrested or cholesterol-enriched cells and required metabolic energy. In contrast, cholesterol efflux by apolipoprotein-depleted acceptors did not depend on cell growth state, cholesterol enrichment, or metabolic energy. Apolipoprotein-mediated efflux was not observed at temperatures below 22≡C, while apolipoprotein-independent efflux was only reduced by 50% at 4°C compared with incubations at 37°C. Additionally, apolipoproteins promoted a more rapid and larger decrease in intracellular cholesteryl esters when measured by changes in cholesteryl ester radioactivity, mass, or the pool of cholesterol available for esterification by acyl coenzyme A:cholesterol acyltransferase. Efflux of excess cellular cholesterol by an apolipoprotein-dependent pathway appears to involve specific cellular events consistent with the properties of an active transport pathway and distinguishable from cholesterol efflux by apolipoprotein-depleted acceptors through passive mechanisms.

KW - Apolipoprotein A-1

KW - Cholesteryl esters

KW - Fibroblasts

KW - High density lipo-proteins

KW - Phospholipid vesicles

UR - http://www.scopus.com/inward/record.url?scp=0030798659&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030798659&partnerID=8YFLogxK

M3 - Article

VL - 38

SP - 1807

EP - 1821

JO - Journal of Lipid Research

JF - Journal of Lipid Research

SN - 0022-2275

IS - 9

ER -