HEPATIC-METABOLISM OF OXIDATIVELY MODIFIED APO E-FREE HIGH-DENSITY-LIPOPROTEINS

Aims/Background: The metabolism of rat apo E-free high-density lipopro teins (HDL) was contrasted with oxidatively modified apo E-free high-d ensity lipoproteins (OX-HDL) in the rat hepatoma cell, Fu5AH. Results: When 10-100 mu g/ml [I-125]-HDL or [I-125]-OX-HDL were incubated with cells for 4 h at 37 degrees C, cellular uptake of oxidized lipoprotei ns was twice control. In contrast, protein degradation was equal. [I-1 25]-HDL or [I-125]-OX-HDL were incubated with the cells for 4 h follow ed by a 4 h chase with unlabeled HDL and OX-HDL, respectively. In thes e experiments. 80% of [I-125]-HDL was resecreted from the cell within 30 min while 50% of [I-125]-OX-HDL was retained by the cell after 2 h. Electron microscopy was used to determine if the OX-HDL was retained in lysosomes. Cells were incubated with gold-labeled OX-HDL; and lysos omes were stained with acid phosphatase. Gold-labeled OX-HDL was abund ant in intracellular vesicles that were not reactive to acid phosphata se. However. Vesicles with a high content of OX-HDL frequently stained positively for 3,3'-diaminobenzidine, a stain that reacts with catala se and is used to detect peroxisomes. Conclusions: The present evidenc e indicates that the cellular metabolism of OX-HDL is different from t hat of unmodified HDL.