Neurotoxicity of cholesterol oxides on cultured cerebellar granule cells.
Cultured rat cerebellar granule cells were used to determine the potential neurotoxicity of cholesterol oxides. The cholesterol oxides tested included: 7-beta-OH-, 7-keto-, 19-OH-, 22(R)-OH-, 22(S)-OH- and 25-OH- cholesterol. Among them, 7-beta-OH- and 7-keto-cholesterol were the most efficacious in causing neuronal death such that 20 microg/ml (50 microM) of these agents killed more than 80% of cells in 2 days. 7-beta-OH-cholesterol at this concentration killed 50% of cells in approximately 7 h. A number of pharmacological agents were tested for their abilities to prevent neuronal death induced by cholesterol oxides. Among them, aurintricarboxylic acid, vitamin E and methyl-beta-cyclodextrin were able to prevent cholesterol oxide-induced neurotoxicity in a dose-dependent manner. These results suggest that, in addition to causing pathological changes in cells directly involved in atherosclerosis, cholesterol oxides may induce toxicity in neurons of the central nervous system.
Chang
J Y
JY
Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
Liu
L Z
LZ
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001312:Aurintricarboxylic Acid / Q000494:pharmacology; D016923:Cell Death; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects*; D000242:Cyclic AMP / Q000494:pharmacology; D003505:Cyclodextrins / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004347:Drug Interactions; D006888:Hydroxycholesterols / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000494:pharmacology; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D006888:Hydroxycholesterols; D011500:Protein Synthesis Inhibitors; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D014810:Vitamin E; D001312:Aurintricarboxylic Acid; C007997:25-hydroxycholesterol; D003513:Cycloheximide; D000242:Cyclic AMP; D001205:Ascorbic Acid