Serum amyloid A promotes ABCA1-dependent and ABCA1-independent lipid efflux from cells.
Serum amyloid A (SAA) is an acute phase protein that associates with HDL. In order to examine the role of SAA in reverse-cholesterol transport, lipid efflux was tested to SAA from HeLa cells before and after transfection with the ABCA1 transporter. ABCA1 expression increased efflux of cholesterol and phospholipid to SAA by 3-fold and 2-fold, respectively. In contrast to apoA-I, SAA also removed lipid without ABCA1; cholesterol efflux from control cells to SAA was 10-fold higher than for apoA-I. Furthermore, SAA effluxed cholesterol from Tangier disease fibroblasts and from cells after inhibition of ABCA1 by fixation with paraformaldehyde. In summary, SAA can act as a lipid acceptor for ABCA1, but unlike apoA-I, it can also efflux lipid without ABCA1, by most likely a detergent-like extraction process. These results suggest that SAA may play a unique role as an auxiliary lipid acceptor in the removal of lipid from sites of inflammation.
Stonik
John A
JA
National Institutes of Health Molecular Disease Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, USA.
Remaley
Alan T
AT
Demosky
Steve J
SJ
Neufeld
Edward B
EB
Bocharov
Alexander
A
Brewer
H Bryan
HB
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D001053:Apolipoproteins / Q000235:genetics / Q000378:metabolism*; D001693:Biological Transport, Active; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D050356:Lipid Metabolism; D010743:Phospholipids / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000235:genetics / Q000378:metabolism*; D013631:Tangier Disease / Q000235:genetics / Q000378:metabolism; D014162:Transfection
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D001053:Apolipoproteins; D010743:Phospholipids; D011994:Recombinant Proteins; D000685:Serum Amyloid A Protein; D002784:Cholesterol