Regulation of cellular cholesterol efflux by lecithin:cholesterol acyltransferase reaction through nonspecific lipid exchange.
Erythrocyte was found lacking in reactivity to lipid-free apolipoproteins to generate pre-beta-high density lipoprotein (HDL) with the cellular lipid and, therefore, was used to study cellular cholesterol efflux to plasma lipoproteins exclusively by a nonspecific exchange mechanism. Over the range of hematocrit from 1-20% (cellular cholesterol pool of 2.5 micrograms per 250 microliters), the fractional rate of cellular cholesterol efflux to lipoprotein was constant, and, therefore, absolute efflux rate was a linear function of the hematocrit of this range. In the absence of lecithin:cholesterol acyltransferase (LCAT), the cholesterol influx rate from lipoproteins was equal to the efflux rate from erythrocyte resulting in no net transfer of cholesterol, with either HDL or low density lipoprotein. In the presence of LCAT in the mixture of HDL and erythrocyte, cholesterol was esterified exclusively in HDL regardless of the origin. When the hematocrit was low and efflux of cellular cholesterol was slower than cholesterol esterification, the esterification of cell-originating cholesterol did not directly enhance the efflux. With high hematocrit that gives faster cholesterol efflux, the efflux was increased directly by the cholesterol esterification. On the other hand, the LCAT reaction significantly reduced HDL-cholesterol influx. The LCAT reaction thus induces substantial net cholesterol efflux from erythrocytes through a nonspecific cholesterol exchange mechanism.
Czarnecka
H
H
Lipid and Lipoprotein Research Group, University of Alberta, Edmonton, Canada.
Yokoyama
S
S
D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D004910:Erythrocyte Membrane / Q000378:metabolism*; D006400:Hematocrit; D006801:Humans; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism*; D013552:Swine
D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase