25-Hydroxycholesterol causes death but does not prevent nerve growth factor-induced neurite outgrowth in PC12 cells

The effects of cholesterol oxides on regular and neuronal PC12 cells were examined. Among the cholesterol oxides tested, 7-beta-, 22(R)- and 25-OH-cholesterol were very toxic to regular PC12 cells such that approximately 80% of cells were killed after a 3 day incubation with 20 micrograms/ml (50 microM) of these agents. Cholesterol oxides caused cytotoxicity in neuronal PC12 cells at concentrations higher than those observed for regular PC12 cells. The nerve growth factor (NGF)-induced neurite outgrowth and nitric oxide synthase expression appeared normal in PC12 cells treated with a sublethal dose of 25-OH-cholesterol. Neurite regeneration from established neuronal PC12 cells was not inhibited by the presence of a toxic dose of 25-OH-cholesterol. Given the fact that 25-OH-cholesterol is a potent inhibitor of cholesterol synthesis pathway, these results suggest that the de novo synthesis of cholesterol may not be required for NGF-induced neurite outgrowth in PC12 cells.