TY - JOUR
T1 - Enhancement of scavenger receptor class B type I-mediated selective cholesteryl ester uptake from apoA-I-/- high density lipoprotein (HDL) by apolipoprotein A-I requires HDL reorganization by lecithin cholesterol acyltransferase
AU - Temel, Ryan E.
AU - Parks, John S.
AU - Williams, David L.
PY - 2003/2/14
Y1 - 2003/2/14
N2 - The severe depletion of cholesteryl ester (CE) in adrenocortical cells of apoA-I-/- mice suggests that apolipoprotein (apo) A-I plays an important role in the high density lipoprotein (HDL) CE selective uptake process mediated by scavenger receptor BI (SR-BI) in vivo. A recent study showed that apoA-I-/- HDL binds to SR-BI with the same affinity as apoA-I+/+ HDL, but apoA-I-/- HDL has a decreased Vmax for CE transfer from the HDL particle to adrenal cells. The present study was designed to determine the basis for the reduced selective uptake of CE from apoA-I-/- HDL. Variations in apoA-I-/- HDL particle diameter, free cholesterol or phospholipid content, or the apoE or apoA-II content of apoA-I-/- HDL had little effect on HDL CE selective uptake into Y1-BS1 adrenal cells. Lecithin cholesterol acyltransferase treatment alone or addition of apoA-I to apoA-I-/- HDL alone also had little effect. However, addition of apoA-I to apoA-I-/- HDL in the presence of lecithin cholesterol acyltransferase reorganized the large heterogeneous apoA-I-/- HDL to a more discrete particle with enhanced CE selective uptake activity. These results show a unique role for apoA-I in HDL CE selective uptake that is distinct from its role as a ligand for HDL binding to SR-BI. These data suggest that the conformation of apoA-I at the HDL surface is important for the efficient transfer of CE to the cell.
AB - The severe depletion of cholesteryl ester (CE) in adrenocortical cells of apoA-I-/- mice suggests that apolipoprotein (apo) A-I plays an important role in the high density lipoprotein (HDL) CE selective uptake process mediated by scavenger receptor BI (SR-BI) in vivo. A recent study showed that apoA-I-/- HDL binds to SR-BI with the same affinity as apoA-I+/+ HDL, but apoA-I-/- HDL has a decreased Vmax for CE transfer from the HDL particle to adrenal cells. The present study was designed to determine the basis for the reduced selective uptake of CE from apoA-I-/- HDL. Variations in apoA-I-/- HDL particle diameter, free cholesterol or phospholipid content, or the apoE or apoA-II content of apoA-I-/- HDL had little effect on HDL CE selective uptake into Y1-BS1 adrenal cells. Lecithin cholesterol acyltransferase treatment alone or addition of apoA-I to apoA-I-/- HDL alone also had little effect. However, addition of apoA-I to apoA-I-/- HDL in the presence of lecithin cholesterol acyltransferase reorganized the large heterogeneous apoA-I-/- HDL to a more discrete particle with enhanced CE selective uptake activity. These results show a unique role for apoA-I in HDL CE selective uptake that is distinct from its role as a ligand for HDL binding to SR-BI. These data suggest that the conformation of apoA-I at the HDL surface is important for the efficient transfer of CE to the cell.
UR - http://www.scopus.com/inward/record.url?scp=0012642388&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0012642388&partnerID=8YFLogxK
U2 - 10.1074/jbc.M208160200
DO - 10.1074/jbc.M208160200
M3 - Article
C2 - 12473673
AN - SCOPUS:0012642388
SN - 0021-9258
VL - 278
SP - 4792
EP - 4799
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 7
ER -