The C-terminal domain of apolipoprotein A-I is involved in ABCA1-driven phospholipid and cholesterol efflux.
ABCA1, a member of the ATP-binding cassette family, mediates the efflux of cellular lipids to free apolipoproteins, mainly apoA-I. The role of the C-terminal domain of apoA-I in this process has been evaluated by measuring the efflux capacity of a truncated form (apoA-I-(1-192)) versus intact apoA-I in different cellular models. In stimulated J774 macrophages, cholesterol efflux to apoA-I-(1-192) was remarkably lower than that to the intact apoA-I. The truncated apoA-I, lacking an important lipid-binding domain, was also significantly less efficient in removing phospholipids from stimulated macrophages. No difference was detected with stimulated Tangier fibroblasts that do not express functional ABCA1. The C-terminal domain of apoA-I is clearly involved in ABCA1-driven lipid efflux. Independent of the interaction with the cell surface, it may be the decreased ability of the truncated apoA-I to recruit membrane phospholipids that impairs its capacity to promote cell cholesterol efflux.
Favari
Elda
E
Department of Pharmacological and Biological Sciences, and Applied Chemistry, University of Parma, Parco Area delle Scienze 27/A, 43100 Parma, Italy.
Bernini
Franco
F
Tarugi
Patrizia
P
Franceschini
Guido
G
Calabresi
Laura
L
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D016632:Apolipoprotein A-I / Q000737:chemistry* / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051381:Rats; D014407:Tumor Cells, Cultured
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D010446:Peptide Fragments; D010743:Phospholipids; D002784:Cholesterol