Most peripheral cells generate cholesterol-rich high-density lipoprotein (HDL) with exogenous apolipoprotein as one of the mechanisms for the maintenance of cellular cholesterol homeostasis. Astrocytes isolated from fetal rat brain showed a unique behavior in this reaction. Consistent with previous findings, the astrocytes synthesized apolipoprotein (apo) E and generated cholesterol-rich pre-beta-HDL-like lipoprotein with this apoE, and cellular cholesterol and phospholipids. When exogenous apoA-I and E were added to the medium, they caused generation of additional HDL with cellular phospholipid. It is interesting that this additional part was very poor in cholesterol except for the generation of relatively cholesterol-rich HDL only in the initial few hours of the incubation. The mobilization of intracellular cholesterol for this reaction was also very limited, reflecting the poor cholesterol incorporation into the HDL. Thus, the results demonstrated a unique profile of HDL generation and cholesterol efflux by apolipoproteins in rat astrocytes, with endogenous apoE producing cholesterol-rich HDL and exogenous apolipoproteins producing cholesterol-poor HDL. These lipoproteins may play differential roles in cholesterol transport in the CNS.
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