Journal of Lipid Research, Vol 31, 1821-1830, Copyright © 1990 by Lipid Research, Inc.
Inhibition of cholesterol synthesis and esterification regulates high density lipoprotein interaction with isolated epithelial cells of human small intestine
DD Sviridov, MY Pavlov, IG Safonova, VS Repin and VN Smirnov
Institute of Experimental Cardiology, National Cardiology Research Center, Moscow, USSR.
The effect of two inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A
(HMG-CoA) reductase, lovastatin and monacolin L, and an inhibitor of acyl
coenzyme A:cholesterol acyltransferase (ACAT), Sandoz compound 58- 035, on
the interaction of 125I-labeled high density lipoprotein-3 (HDL3) with
isolated human enterocytes was studied. Both HMG-CoA reductase inhibitors
inhibited cholesterol synthesis and 125I-labeled HDL3 binding and
degradation by enterocytes; a strong correlation between changes in
cholesterol synthesis and interaction of 125I- labeled HDL3 with cells was
observed. Lovastatin caused reduction of the apparent number of
125I-labeled HDL3 binding sites without affecting the binding affinity. No
changes of cell cholesterol content were observed after incubation of cells
with lovastatin. Mevalonic acid reversed the effect of lovastatin on
125I-labeled HDL3 binding. Lovastatin blocked up-regulation of the HDL
receptor in response to loading of cells with nonlipoprotein cholesterol
and modified cholesterol-induced changes of 125I-labeled HDL3 degradation.
Lovastatin also reduced HDL-mediated efflux of endogenously synthesized
cholesterol from enterocytes. The ACAT inhibitor caused a modest increase
of 125I-labeled HDL3 binding to enterocytes and significantly decreased its
degradation; both effects correlated with inhibition of cholesteryl ester
synthesis. The results allow us to assume that the intracellular free
cholesterol pool may play a key role in regulation of the HDL receptor.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
