Cholesterol efflux from adipose cells is coupled to diacylglycerol production and protein kinase C activation.
Apolipoprotein A-I (apo A-I)*/DMPC complexes have been previously shown to promote cholesterol efflux from cholesterol-preloaded adipose cells whereas apo A-II/DMPC complexes, which bind to the same cell surface binding sites, were ineffective. Addition of apo A-I/DMPC complexes led to a rapid and transient formation of diacylglycerol. However, in contrast to PGF2 alpha (Doglio et al., Proc. Natl. Acad. Sci. USA, 1989, 86, 1148), no accumulation of inositol phosphates was observed. Apo A-II/DMPC complexes had no effect on diacylglycerol formation. Stimulation by apo A-I/DMPC complexes or native HDL3 of cells prelabelled with (2-palmitoyl 9,10[3H])phosphatidylcholine induced also the formation of labelled diacylglycerol whereas apo A-II/DMPC complexes and HDL3 treated with tetranitromethane showed no effect. Direct activation of protein kinase C(s) by PMA promoted cholesterol efflux providing that DMPC liposomes were present as cholesterol acceptor. It is proposed that lipoprotein particles have two separate effects, i.e. a ligand-induced effect leading to cholesterol translocation from intracellular stores to the cell surface and a bilayer-induced effect allowing cholesterol efflux from the cell surface to the acceptor.
Theret
N
N
SERLIA, U325 INSERM, Institut Pasteur, Lille, France.
Delbart
C
C
Aguie
G
G
Fruchart
J C
JC
Vassaux
G
G
Ailhaud
G
G
D000273:Adipose Tissue / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D001053:Apolipoproteins / Q000097:blood; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism*; D004134:Dimyristoylphosphatidylcholine / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008051:Lipid Bilayers / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*
C011439:1,2-diacylglycerol; D001053:Apolipoproteins; D004075:Diglycerides; D008051:Lipid Bilayers; D010703:Phorbol Esters; D002784:Cholesterol; D011493:Protein Kinase C; D004134:Dimyristoylphosphatidylcholine