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Impaired ATP-binding cassette transporter A1-mediated sterol efflux from oxidized LDL-loaded macrophages |
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| Authors: | Favari Elda Zimetti Francesca Bortnick Anna E Adorni Maria Pia Zanotti Ilaria Canavesi Monica Bernini Franco |
| Institution: | Department of Pharmacological and Biological Sciences, and Applied Chemistries, University of Parma, Area delle Scienze 27/A, 43100 Parma, Italy. |
| 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: | ABCA1 ATP-binding cassette A1 AcLDL acetylated low density lipoprotein apo-AI apolipoprotein AI BSA bovine serum albumin 9cRA 9-cis retinoic acid cpt-cAMP 8-(4-chlorophenylthio)adenosine 3′:5′-cyclic monophosphate CE cholesteryl ester FCS fetal calf serum FC free cholesterol LDL low density lipoprotein 22-OH 22 (R)-hydroxycholesterol MPM mouse peritoneal macrophages PBS phosphate buffer saline PMA phorbol 12-myristate 13-acetate OxLDL oxidized low density lipoprotein 7K 7-ketocholesterol |
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