THE ENHANCED ASSOCIATION OF APOLIPOPROTEIN-E WITH APOLIPOPROTEIN B-CONTAINING LIPOPROTEINS IN SERUM-STIMULATED HEPATOCYTES OCCURS INTRACELLULARLY

Synthesis and secretion of VLDL in HepG2 cells are stimulated by sever al lipogenic factors, including serum. We previously found that the am ount of apolipoprotein (ape) E associated with large lipoproteins such as VLDL increased under conditions of stimulated lipogenesis. The pre sent study was designed to determine if the increased apoE association with VLDL occurs intracellularly or after secretion. In addition to H epG2 we studied rat hepatoma McA-RH7777 cells for production of endoge nous rat apoE and transfected human apoE3. In both hepatoma cell lines stimulation of lipogenesis and production of large apoB-containing li poproteins by serum resulted in increased apoE association with these particles and in decreased apoE association with HDL without affecting the total apoE output. Although evidence of apoE redistribution was s een among lipoproteins in the media, the apoE newly secreted under con ditions of stimulated lipogenesis mainly associated with apoB-containi ng lipoproteins at the expense of its association with HDL. However, t his effect was not attributable to reduced HDL lipid and apoA-I mass. Finally, redistribution of apoE from HDL to apoB-containing lipoprotei ns was also observed intracellularly in both HepG2 and transfected McA -RH7777 cells expressing human apoE3. These data suggest that the redi stribution of apoE from HDL to apoB-containing lipoproteins upon activ ated lipogenesis in hepatoma cells occurs intracellularly and is not a ttributable to a decrease in HDL production.