Effects of apolipoproteins A-IV and A-I on the uptake of phospholipid liposomes by hepatocytes.
We examined the effects of apolipoproteins A-IV and A-I on the catabolism of whole particles by hepatoma G2 cells and cultured primary hepatocytes. For this type of experiment, high density lipoprotein is unsuitable, because all of its lipid and protein components independently dissociate and exchange and hence poorly trace whole particle catabolism. We therefore used phosphatidylcholine liposomes with radioactive tracers entrapped within their aqueous cores. Apolipoproteins A-IV, A-I, or E added to liposomes became liposome-associated and produced no detectable release of encapsulated label. As a positive control, apolipoprotein E doubled the uptake of labeled liposomes by hepatoma cells, compared to apolipoprotein-free controls, and this increase could be blocked by the addition of excess unlabeled low density lipoprotein. Degradation of labeled liposomes by hepatoma cells was increased 6-fold by the addition of apolipoprotein E. In contrast, neither apolipoprotein A-IV nor A-I increased cellular uptake or degradation of the particles. Similar results were obtained with primary hepatocytes. In studies using apolipoprotein combinations, apolipoproteins A-IV and A-I were each able to displace apolipoprotein E from liposomes and thereby reduce cellular uptake. Our data indicate that apolipoproteins A-IV and A-I do not facilitate uptake or degradation of whole particles by liver-derived cells in vitro. However, these apolipoproteins may modulate receptor-mediated uptake of particles by reducing the amount of particle-bound apolipoprotein E.
Bisgaier
C L
CL
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032.
Siebenkas
M V
MV
Williams
K J
KJ
D000818:Animals; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000502:physiology*; D001057:Apolipoproteins E / Q000502:physiology; D001692:Biological Transport; D002478:Cells, Cultured; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000502:physiology*; D008081:Liposomes; D008099:Liver / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D012016:Reference Values
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D001057:Apolipoproteins E; D008075:Lipoproteins, HDL; D008081:Liposomes; D010743:Phospholipids; C022205:apolipoprotein A-IV