Cholesterol homeostasis in rat astrocytoma cells GA-1

Astrocytes play a key role in cholesterol metabolism in central nervous system. We have shown that fetal rat astrocytes in primary culture secrete cholesterol-rich HDL with the endogenous apolipoprotein (apo) E and generate cholesterol-poor HDL with exogenous apoE and apoA-I Ito et al. (1999) J. Neurochem. 72, 2362]. In order to study these reactions in relation to the stage of cell differentiation, we examined generation of HDL by rat astrocytoma cells. Lack of apoE secretion was found in three astrocytoma cell lines, human T98G, rat C6, and GA-1 Kano-Tanaka et al. (1986) Proc. Jpn. Acad. Ser. B 62, 109]. GA-1 produced apoE at very low level and therefore generated much less HDL by itself than the astrocytes in primary culture. In contrast, GA-1 interacted with exogenous apoE and apoA-I to produce cholesterol-rich HDL while the astrocytes produced cholesterol-poor HDL with these apolipoproteins. Cholesterol biosynthesis rate measured from mevalonate was higher and down-regulated more by LDL in the astrocytes than GA-1. On the other hand, the cellular cholesterol level, uptake of LDL, and cyclodextrin-mediated non-specific diffusion of cholesterol from cell surface were same between these two cells. Treatment of GA-1 with acidic fibroblast growth factor influenced neither the production of apoE nor the baseline lipid secretion, but increased the cholesterol synthesis from mevalonate and the magnitude of its down-regulation by LDL, and decreased cholesterol content in the HDL produced by exogenous apoA-I. In conclusion, suppression of apoE biosynthesis in the undifferentiated astrocytes GA-1 resulted in poor secretion of cholesterol-rich HDL and in turn more production of HDL with exogenous apolipoprotein. Cellular cholesterol homeostasis was altered accordingly.