Regulation of cholesterol metabolism and low-density lipoprotein binding in human intestinal Caco-2 cells.
In the present paper, the regulation of 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase, acylcoenzyme A cholesterol acyltransferase (ACAT) and low-density lipoprotein (LDL) binding was studied in the human colon cancer carcinoma cell line Caco-2. LDL down-regulated HMG-CoA reductase activity in a dose-dependent fashion to a minimum of 28% of control at 200 micrograms/ml and LDL binding to 52% of control. The activity of ACAT was stimulated by LDL. High-density lipoprotein 3 (HDL3) increased HMG-CoA reductase activity, whereas cholesteryl ester formation was slightly decreased. Inhibition of the endogenous cholesterol biosynthesis by mevinolin increased both LDL binding and activity of HMG-CoA reductase. This effect was reversed by the addition of mevalonolactone but not by LDL. It is concluded that regulation of HMG-CoA reductase and LDL binding is subject to the availability of non-sterol products of mevalonic acid and of exogenous cholesterol. ACAT is regulated mainly by the level of its substrate cholesterol.
Reimann
F M
FM
Department of Internal Medicine II, University of Ulm, FRG.
Herold
G
G
Grosshans
I
I
Rogler
G
G
Fellermann
K
K
Stange
E F
EF
D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008148:Lovastatin / Q000494:pharmacology; D008798:Mevalonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D011869:Radioligand Assay; D002785:Sterol O-Acyltransferase / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; C015367:mevalonolactone; D002784:Cholesterol; D008148:Lovastatin; D006903:Hydroxymethylglutaryl CoA Reductases; D002785:Sterol O-Acyltransferase; D008798:Mevalonic Acid