Human apolipoprotein A-IV binds to apolipoprotein A-I/A-II receptor sites and promotes cholesterol efflux from adipose cells.
Cholesterol efflux was studied in cultured mouse adipose cells after preloading with low density lipoprotein cholesterol. Exposure to complexes containing human apolipoprotein A-IV and L-alpha-dimyristoylphosphatidylcholine (DMPC) as well as to human lipoprotein particles containing apolipoprotein A-IV but not apolipoprotein A-I and particles containing apolipoproteins A-IV and A-I showed that both artificial and native apolipoprotein A-IV-containing particles were able to promote cholesterol efflux at 37 degrees C as a function of time and concentration. The half-maximal concentration was found to be 0.3 X 10(-6) M for apolipoprotein A-IV.DMPC complexes. Binding experiments performed in intact cells at 4 degrees C with labeled apolipoprotein A-IV.DMPC complexes showed the existence of specific binding sites, with a Kd value of 0.32 x 10(-6) M and a maximal binding capacity of 223,000 sites/cell. By cross-competition experiments with labeled and unlabeled complexes containing apolipoprotein A-IV, A-I, or A-II, it appeared that all three apolipoproteins bind to the same cell-surface recognition sites. It is suggested that apolipoprotein A-IV, which is present in the interstitial fluid surrounding adipose cells in vivo at concentrations similar to those required in vitro for the promotion of cholesterol efflux, plays a critical role in cholesterol removal from peripheral cells.
Steinmetz
A
A
SERLIA, Institut Pasteur, Lille, France.
Barbaras
R
R
Ghalim
N
N
Clavey
V
V
Fruchart
J C
JC
Ailhaud
G
G
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D001054:Apolipoproteins A / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D001667:Binding, Competitive; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D004134:Dimyristoylphosphatidylcholine / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D051379:Mice; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018110:Receptors, Lipoprotein
D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D001054:Apolipoproteins A; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein; C064018:apolipoprotein A-I A-II receptor; C022205:apolipoprotein A-IV; D002784:Cholesterol; D004134:Dimyristoylphosphatidylcholine