Impaired ATP-binding cassette transporter A1-mediated sterol efflux from oxidized LDL-loaded macrophages

Elda Favari; Francesca Zimetti; Anna E. Bortnick; Maria Pia Adorni; Ilaria Zanotti; Monica Canavesi; Franco Bernini

doi:10.1016/j.febslet.2005.10.042

Impaired ATP-binding cassette transporter A1-mediated sterol efflux from oxidized LDL-loaded macrophages

Elda Favari, Francesca Zimetti, Anna E. Bortnick, Maria Pia Adorni, Ilaria Zanotti, Monica Canavesi, Franco Bernini

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

We investigated the interaction of oxidized low density lipoprotein (OxLDL) with the ATP-binding cassette A1 (ABCA1) pathway in J774 macrophages. Cellular efflux to apolipoprotein AI (apo-AI) of OxLDL-derived cholesterol was lower than efflux of cholesterol derived from acetylated low density lipoprotein (AcLDL). ABCA1 upregulation by 8-(4-chlorophenylthio)adenosine 3′:5′-cyclic monophosphate (cpt-cAMP) or 22 (R)-hydroxycholesterol (22-OH) and 9-cis retinoic acid (9cRA) increased the efflux to apo-AI of cellular sterols derived from AcLDL, but not of those from OxLDL. AcLDL, but not OxLDL, induced ABCA1 protein content and activity in J774. However, OxLDL did not influence J774 ABCA1 upregulation by cpt-cAMP or 22-OH/9cRA. We conclude that sterols released to cells by OxLDL are available neither as substrate nor as modulator of ABCA1.

Original language	English (US)
Pages (from-to)	6537-6542
Number of pages	6
Journal	FEBS Letters
Volume	579
Issue number	29
DOIs	https://doi.org/10.1016/j.febslet.2005.10.042
State	Published - Dec 5 2005
Externally published	Yes

Keywords

ATP-binding cassette A1
Atherosclerosis
Cholesterol efflux
Foam cells
Macrophages
Oxidized low density lipoprotein

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/j.febslet.2005.10.042

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title = "Impaired ATP-binding cassette transporter A1-mediated sterol efflux from oxidized LDL-loaded macrophages",

abstract = "We investigated the interaction of oxidized low density lipoprotein (OxLDL) with the ATP-binding cassette A1 (ABCA1) pathway in J774 macrophages. Cellular efflux to apolipoprotein AI (apo-AI) of OxLDL-derived cholesterol was lower than efflux of cholesterol derived from acetylated low density lipoprotein (AcLDL). ABCA1 upregulation by 8-(4-chlorophenylthio)adenosine 3′:5′-cyclic monophosphate (cpt-cAMP) or 22 (R)-hydroxycholesterol (22-OH) and 9-cis retinoic acid (9cRA) increased the efflux to apo-AI of cellular sterols derived from AcLDL, but not of those from OxLDL. AcLDL, but not OxLDL, induced ABCA1 protein content and activity in J774. However, OxLDL did not influence J774 ABCA1 upregulation by cpt-cAMP or 22-OH/9cRA. We conclude that sterols released to cells by OxLDL are available neither as substrate nor as modulator of ABCA1.",

keywords = "ATP-binding cassette A1, Atherosclerosis, Cholesterol efflux, Foam cells, Macrophages, Oxidized low density lipoprotein",

author = "Elda Favari and Francesca Zimetti and Bortnick, {Anna E.} and Adorni, {Maria Pia} and Ilaria Zanotti and Monica Canavesi and Franco Bernini",

note = "Funding Information: The work was supported by grants from Compagnia di San Paolo, the Istituto Nazionale Ricerche Cardiovascolari and the Italian Ministry of University and Scientific Research.",

year = "2005",

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T1 - Impaired ATP-binding cassette transporter A1-mediated sterol efflux from oxidized LDL-loaded macrophages

AU - Favari, Elda

AU - Zimetti, Francesca

AU - Bortnick, Anna E.

AU - Adorni, Maria Pia

AU - Zanotti, Ilaria

AU - Canavesi, Monica

AU - Bernini, Franco

N1 - Funding Information: The work was supported by grants from Compagnia di San Paolo, the Istituto Nazionale Ricerche Cardiovascolari and the Italian Ministry of University and Scientific Research.

PY - 2005/12/5

Y1 - 2005/12/5

N2 - We investigated the interaction of oxidized low density lipoprotein (OxLDL) with the ATP-binding cassette A1 (ABCA1) pathway in J774 macrophages. Cellular efflux to apolipoprotein AI (apo-AI) of OxLDL-derived cholesterol was lower than efflux of cholesterol derived from acetylated low density lipoprotein (AcLDL). ABCA1 upregulation by 8-(4-chlorophenylthio)adenosine 3′:5′-cyclic monophosphate (cpt-cAMP) or 22 (R)-hydroxycholesterol (22-OH) and 9-cis retinoic acid (9cRA) increased the efflux to apo-AI of cellular sterols derived from AcLDL, but not of those from OxLDL. AcLDL, but not OxLDL, induced ABCA1 protein content and activity in J774. However, OxLDL did not influence J774 ABCA1 upregulation by cpt-cAMP or 22-OH/9cRA. We conclude that sterols released to cells by OxLDL are available neither as substrate nor as modulator of ABCA1.

AB - We investigated the interaction of oxidized low density lipoprotein (OxLDL) with the ATP-binding cassette A1 (ABCA1) pathway in J774 macrophages. Cellular efflux to apolipoprotein AI (apo-AI) of OxLDL-derived cholesterol was lower than efflux of cholesterol derived from acetylated low density lipoprotein (AcLDL). ABCA1 upregulation by 8-(4-chlorophenylthio)adenosine 3′:5′-cyclic monophosphate (cpt-cAMP) or 22 (R)-hydroxycholesterol (22-OH) and 9-cis retinoic acid (9cRA) increased the efflux to apo-AI of cellular sterols derived from AcLDL, but not of those from OxLDL. AcLDL, but not OxLDL, induced ABCA1 protein content and activity in J774. However, OxLDL did not influence J774 ABCA1 upregulation by cpt-cAMP or 22-OH/9cRA. We conclude that sterols released to cells by OxLDL are available neither as substrate nor as modulator of ABCA1.

KW - ATP-binding cassette A1

KW - Atherosclerosis

KW - Cholesterol efflux

KW - Foam cells

KW - Macrophages

KW - Oxidized low density lipoprotein

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JO - FEBS Letters

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Impaired ATP-binding cassette transporter A1-mediated sterol efflux from oxidized LDL-loaded macrophages

Abstract

Keywords

ASJC Scopus subject areas

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