Cholesterol esters regulate apoB 48 secretion in CaCo 2 cells

Abstract

In this study, we investigated the effect of atorvastatin, an HMG-CoA reductase inhibitor and CL277082, an ACAT inhibitor, on apolipoprotein B 48 synthesis, degradation and secretion in transformed human intestinal enterocytes (CaCo 2 cells). Cells were incubated with atorvastatin or CL277082 in the absence or presence of sterol containing media and pulsed with [S 35]-methionine and chased with unlabelled methionine. Concomitantly, the effect of atorvastatin and CL277082 on the relative amount of apoB 48 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 apoB 48 from CaCo 2 cells under basal conditions. On the other hand, suppression of cholesterol biosynthesis with atorvastatin under stimulatory conditions accelerated the degradation of apoB 48 in cells without affecting its synthesis or secretion. There was no effect of exogenous sterols on apoB 48 secretion. Taken together, neither endogenous nor exogenous cholesterol appears to acutely modulate apoB 48 secretion from intestinal cells. In contrast, inhibition of cholesterol esterification with ACAT inhibitor significantly attenuated apoB 48 secretion under basal and stimulatory conditions by a mechanism which enhanced apoB 48 degradation. Collectively, our results suggest that in CaCo 2 cells, newly synthesized cholesterol ester may be an immediate regulator apoB 48 secretion.