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Impaired ATP‐binding cassette transporter A1‐mediated sterol efflux from oxidized LDL‐loaded macrophages
Author(s) -
Favari Elda,
Zimetti Francesca,
Bortnick Anna E.,
Adorni Maria Pia,
Zanotti Ilaria,
Canavesi Monica,
Bernini Franco
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.10.042
Subject(s) - abca1 , atp binding cassette transporter 1 , efflux , downregulation and upregulation , cholesterol , chemistry , lipoprotein , biochemistry , apolipoprotein b , atp binding cassette transporter , sterol , low density lipoprotein , transporter , gene
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.