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An inhibitor of acylCoA: cholesterol acyltransferase increases expression of ATP-binding cassette transporter A1 and thereby enhances the ApoA-I-mediated release of cholesterol from macrophages

Sugimoto, Kanami, Tsujita, Maki, Wu, Cheng-Ai, Suzuki, Kazuo, Yokoyama, Shinji·2004·Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
DOI 10.1016/j.bbalip.2003.12.005
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Abstract

The effect of inhibition of acylCoA: cholesterol acyltransferase (ACAT) was studied on high density lipoprotein (HDL) metabolism. An inhibitor of ACAT, MCC-147, was given mouse peritoneal macrophages and expression of ATP-binding cassette transporter A1 (ABCA1) was examined. ABCA1 was increased both at the mRNA and protein levels, only when the cells are cholesterol-loaded and thereby the inhibitor decreased esterified cholesterol and increased unesterified cholesterol. In this condition, the ACAT inhibitor increased reversible binding of apoA-I to the cells and enhanced apoA-I-mediated release of cellular cholesterol and phospholipid, but did not influence nonspecific cellular cholesterol efflux to lipid microemulsion. It was therefore concluded that the ACAT inhibitor increased the release of cholesterol from the cholesterol-loaded macrophages by increasing the expression of ABCA1, putatively through shifting cholesterol distribution from the esterified to the free compartments.

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Metadata

Authors
Sugimoto, K., Tsujita, M., Wu, C.-A., Suzuki, K., & Yokoyama, S.
Venue
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
Publisher
Elsevier BV
Published
2004-02
Volume
1636
Issue
1
Pages
69-76
ISSN
1388-1981
DOI
10.1016/j.bbalip.2003.12.005
Cited by
24
References
1
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

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