Cholesterol esters regulate apoB48 secretion in CaCo2 cells.
In this study, we investigated the effect of atorvastatin, an HMG-CoA reductase inhibitor and CL277082, an ACAT inhibitor, on apolipoprotein B48 synthesis, degradation and secretion in transformed human intestinal enterocytes (CaCo2 cells). Cells were incubated with atorvastatin or CL277082 in the absence or presence of sterol containing media and pulsed with [S35]-methionine and chased with unlabelled methionine. Concomitantly, the effect of atorvastatin and CL277082 on the relative amount of apoB48 protein in cells and media was also quantified by western blotting using an apoB antibody and enhanced chemiluminescence. Suppression of cholesterol synthesis with atorvastatin did not attenuate the production or secretion of apoB48 from CaCo2 cells under basal conditions. On the other hand, suppression of cholesterol biosynthesis with atorvastatin under stimulatory conditions accelerated the degradation of apoB48 in cells without affecting its synthesis or secretion. There was no effect of exogenous sterols on apoB48 secretion. Taken together, neither endogenous nor exogenous cholesterol appears to acutely modulate apoB48 secretion from intestinal cells. In contrast, inhibition of cholesterol esterification with ACAT inhibitor significantly attenuated apoB48 secretion under basal and stimulatory conditions by a mechanism which enhanced apoB48 degradation. Collectively, our results suggest that in CaCo2 cells, newly synthesized cholesterol ester may be an immediate regulator apoB48 secretion.
Pal
Sebely
S
Department of Nutrition, Dietetics and Food Sciences, Curtin University of Technology, GPO Box U1987, Perth, WA, Australia.
Allister
Emma
E
Thomson
Andrew
A
Mamo
John C L
JC
D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000096:biosynthesis* / Q000378:metabolism; D000069059:Atorvastatin; D018938:Caco-2 Cells; D002784:Cholesterol / Q000096:biosynthesis; D002788:Cholesterol Esters / Q000096:biosynthesis*; D003470:Culture Media; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D050356:Lipid Metabolism; D008715:Methionine / Q000378:metabolism; D010671:Phenylurea Compounds / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors
D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D002788:Cholesterol Esters; D003470:Culture Media; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010671:Phenylurea Compounds; D011758:Pyrroles; C050492:CL 277082; D002784:Cholesterol; D000069059:Atorvastatin; D008715:Methionine; D002785:Sterol O-Acyltransferase