7-ketocholesterol inhibits VLDL secretion by cultured human and rabbit hepatocytes.

7-ketocholesterol, one of the major product of autoxidation of dietary cholesterol, was found to inhibit secretion of very low density lipoprotein [14C]cholesterol, [14C]triacylglycerol and [35S]apoprotein B,E,C by cultured human and rabbit hepatocytes. A parallel inhibition (about 35%) of cholesterol synthesis but not of triacylglycerol formation was observed. Incubation with 10 micrograms/ml of oxysterol also reduced the total apo-B secretion measured by ELISA and increased intracellular apo-B mRNA level.

VLDL apoprotein secretion and apo-B mRNA level in primary culture of cholesterol-loaded rabbit hepatocytes.

Incubation of cultured rabbit hepatocytes with beta very low density lipoproteins (beta-VLDL) induces a dose-dependent increase in cell cholesterol (CH) content and VLDL apoprotein (apo) B and E secretion without change in apo-B mRNA level. These data suggest that beta-VLDL may exert a stimulatory effect on hepatic apo-B production at the co-translational and/or posttranslational level.