NEUROTOXICITY OF 25-OH-CHOLESTEROL ON NGF-DIFFERENTIATED PC12 CELLS

PC12 cells induced to differentiate with nerve growth factor were used to study the neurotoxicity of 25-OH-cholesterol. This agent induced a dose-and rime-dependent cell death in neuronal PC12 cells. Cells trea ted with this agent showed condensed nuclei, a morphology similar to t hat of cells dying of programmed cell death. However, agents known to prevent neuronal programmed cell death (cyclic AMP, KCl, aurintricarbo xylic acid, and cycloheximide) failed to prevent the 25-OH-cholesterol -mediated cytotoxicity. On the other hand, cell death induced by 25-OH -cholesterol was prevented by treatment with vitamin E and methyl-beta -cyclodextrin. In contrast to observations made in other cell types, w hole-cell patch clamp recording of neuronal PC12 cells revealed that t reatment with 25-OH-cholesterol did not significantly alter calcium in flux through voltage-dependent channels. These results provide the fir st characterization of the toxicity of cholesterol oxides toward neuro nal PC12 cells, which should be useful in future studies on the intera ctions between cholesterol oxides and cells from the nervous system.