Impaired ATP-binding cassette transporter A1-mediated sterol efflux from oxidized LDL-loaded macrophages.
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.
Favari
Elda
E
Department of Pharmacological and Biological Sciences, and Applied Chemistries, University of Parma, Area delle Scienze 27/A, 43100 Parma, Italy.
Zimetti
Francesca
F
Bortnick
Anna E
AE
Adorni
Maria Pia
MP
Zanotti
Ilaria
I
Canavesi
Monica
M
Bernini
Franco
F
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D010743:Phospholipids / Q000378:metabolism; D013261:Sterols / Q000378:metabolism*
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D008077:Lipoproteins, LDL; D010743:Phospholipids; D013261:Sterols; C032629:acetyl-LDL; C099252:oxidized low density lipoprotein; D002784:Cholesterol