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.
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 V(max) 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.
Temel
Ryan E
RE
Department of Pharmacological Sciences, University Medical Center, State University of New York, Stony Brook, New York 11794, USA.
Parks
John S
JS
Williams
David L
DL
D000818:Animals; D016632:Apolipoprotein A-I / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D001692:Biological Transport / Q000235:genetics; D002788:Cholesterol Esters / Q000378:metabolism*; D004789:Enzyme Activation; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism*; D011487:Protein Conformation
D016632:Apolipoprotein A-I; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D007862:Phosphatidylcholine-Sterol O-Acyltransferase