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 time-dependent cell death in neuronal PC12 cells. Cells treated with this agent showed condensed nuclei, a morphology similar to that of cells dying of programmed cell death. However, agents known to prevent neuronal programmed cell death (cyclic AMP, KCl, aurintricarboxylic 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, whole-cell patch clamp recording of neuronal PC12 cells revealed that treatment with 25-OH-cholesterol did not significantly alter calcium influx through voltage-dependent channels. These results provide the first characterization of the toxicity of cholesterol oxides toward neuronal PC12 cells, which should be useful in future studies on the interactions between cholesterol oxides and cells from the nervous system.
Chang
J Y
JY
Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
Phelan
K D
KD
Liu
L Z
LZ
D000818:Animals; D017209:Apoptosis; D001205:Ascorbic Acid / Q000494:pharmacology; D001312:Aurintricarboxylic Acid / Q000494:pharmacology; D001769:Blood; D015220:Calcium Channels / Q000187:drug effects; D002454:Cell Differentiation; D000242:Cyclic AMP / Q000494:pharmacology; D003505:Cyclodextrins / Q000494:pharmacology; D006888:Hydroxycholesterols / Q000494:pharmacology*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D014810:Vitamin E / Q000494:pharmacology; D047392:beta-Cyclodextrins
D015220:Calcium Channels; D003505:Cyclodextrins; D006888:Hydroxycholesterols; D009414:Nerve Growth Factors; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D014810:Vitamin E; D001312:Aurintricarboxylic Acid; D011189:Potassium Chloride; C007997:25-hydroxycholesterol; D000242:Cyclic AMP; D001205:Ascorbic Acid