TY - JOUR
T1 - Effects of high-density lipoprotein2 on cholesterol transport and acyl-coenzyme A:cholesterol acyltransferase activity in P388D1 macrophages
AU - Li, Lei
AU - Pownall, Henry J.
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health (HL-30914, HL-56865). L.L. was a student in the Michael E. DeBakey Graduate Program in Cardiovascular Sciences.
PY - 2001/1/15
Y1 - 2001/1/15
N2 - High-density lipoproteins are the putative vehicles for cholesterol removal from monocyte-derived macrophages, which are an important cell type in all stages of atherosclerosis. The role of HDL2, an HDL subclass that accounts for most variation in plasma HDL-cholesterol concentration, in cholesterol metabolism in monocyte-derived macrophages is not known. In this study, the dose-dependent effects of HDL2 on cellular cholesterol mass, efflux, and esterification, and on cellular cholesteryl ester (CE) hydrolysis using the mouse macrophage P388D1 cell line was investigated. HDL2 at low concentrations (40 μg protein/ml) decreased CE content without affecting cellular free cholesterol content (FC), CE hydrolysis, or cholesterol biosynthesis. In addition, HDL2 at low concentrations reduced cellular acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity and increased FC efflux from macrophages. Thus, HDL2 has two potential roles in reverse cholesterol transport. In one, HDL2 is an acceptor of macrophage FC. In the other, more novel role, HDL2 increases the availability of macrophage FC through the inhibition of ACAT. Elucidation of the mechanism by which HDL2 inhibits ACAT could identify new therapeutic targets that enhance the transfer of cholesterol from macrophages to the liver.
AB - High-density lipoproteins are the putative vehicles for cholesterol removal from monocyte-derived macrophages, which are an important cell type in all stages of atherosclerosis. The role of HDL2, an HDL subclass that accounts for most variation in plasma HDL-cholesterol concentration, in cholesterol metabolism in monocyte-derived macrophages is not known. In this study, the dose-dependent effects of HDL2 on cellular cholesterol mass, efflux, and esterification, and on cellular cholesteryl ester (CE) hydrolysis using the mouse macrophage P388D1 cell line was investigated. HDL2 at low concentrations (40 μg protein/ml) decreased CE content without affecting cellular free cholesterol content (FC), CE hydrolysis, or cholesterol biosynthesis. In addition, HDL2 at low concentrations reduced cellular acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity and increased FC efflux from macrophages. Thus, HDL2 has two potential roles in reverse cholesterol transport. In one, HDL2 is an acceptor of macrophage FC. In the other, more novel role, HDL2 increases the availability of macrophage FC through the inhibition of ACAT. Elucidation of the mechanism by which HDL2 inhibits ACAT could identify new therapeutic targets that enhance the transfer of cholesterol from macrophages to the liver.
KW - Acyl-coenzyme A:cholesterol acyltransferase
KW - Cholesterol transport
KW - Cholesteryl ester
KW - High-density lipoprotein
KW - Macrophage
UR - http://www.scopus.com/inward/record.url?scp=0035863037&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035863037&partnerID=8YFLogxK
U2 - 10.1016/S1388-1981(00)00173-6
DO - 10.1016/S1388-1981(00)00173-6
M3 - Article
C2 - 11341963
AN - SCOPUS:0035863037
SN - 1388-1981
VL - 1530
SP - 111
EP - 122
JO - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
JF - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
IS - 1
ER -