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.
Chang
J Y
JY
Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
Liu
L Z
LZ
D000818:Animals; D016923:Cell Death; D002454:Cell Differentiation; D002784:Cholesterol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006888:Hydroxycholesterols / Q000494:pharmacology* / Q000506:poisoning; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009416:Nerve Regeneration; D016501:Neurites / Q000187:drug effects* / Q000502:physiology*; D009474:Neurons / Q000187:drug effects; D010087:Oxides / Q000494:pharmacology; D016716:PC12 Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D051381:Rats
D006888:Hydroxycholesterols; D009414:Nerve Growth Factors; D010087:Oxides; C007997:25-hydroxycholesterol; D002784:Cholesterol