Document Detail

Neurotoxicity of 24-hydroxycholesterol, an important cholesterol elimination product of the brain, may be prevented by vitamin E and estradiol-17beta.
MedLine Citation:
PMID:  11475014     Owner:  NLM     Status:  MEDLINE    
24-Hydroxycholesterol, the main cholesterol elimination product of the brain is increased in serum of Alzheimer patients. This oxysterol behaves neurotoxic towards the human neuroblastoma cell line, SH-SY5Y. Here we demonstrate, that 24-hydroxycholesterol-induced neurotoxicity in differentiated SH-SY5Y cells was due to apoptosis, as indicated by DNA-fragmentation, caspase-3 activation and a decrease of the mitochondrial membrane potential. Free radicals were generated, resulting in the death of 75% of the cells within 48h; neurotoxicity in differentiated SH-SY5Y cells was partially prevented by physiological concentrations of vitamin E (50-100 microM) in that 75% of the cells survived. Physiological concentrations of estradiol-17beta (1-100nM) elicited a protective effect in differentiated cells, which was not significant; however, in undifferentiated cells a significant protection was noted by this steroid hormone. Vitamin C and melatonin did not prevent 24-hydroxycholesterol-induced neurotoxicity. These in vitro data support the in vivo observed beneficial effects reported as circumstantial evidence of vitamin E and estradiol-17beta treatment in the prevention and therapy of neurodegenerative disease.
H Kölsch; M Ludwig; D Lütjohann; M L Rao
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neural transmission (Vienna, Austria : 1996)     Volume:  108     ISSN:  0300-9564     ISO Abbreviation:  J Neural Transm     Publication Date:  2001  
Date Detail:
Created Date:  2001-07-27     Completed Date:  2001-12-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9702341     Medline TA:  J Neural Transm     Country:  Austria    
Other Details:
Languages:  eng     Pagination:  475-88     Citation Subset:  IM    
Department of Clinical Biochemistry, University of Bonn, Federal Republic of Germany.
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MeSH Terms
Antioxidants / pharmacology*
Ascorbic Acid / pharmacology
Brain / metabolism
Caspase 3
Caspases / metabolism
Estradiol / pharmacology*
Free Radicals / metabolism
Hydroxycholesterols / toxicity*
Melatonin / pharmacology
Membrane Potentials / drug effects,  physiology
Mitochondria / metabolism
Neurons / drug effects*,  metabolism,  pathology
Oxidative Stress / drug effects
Tumor Cells, Cultured
Vitamin E / pharmacology*
Reg. No./Substance:
0/Antioxidants; 0/Free Radicals; 0/Hydroxycholesterols; 1406-18-4/Vitamin E; 474-73-7/24-hydroxycholesterol; 50-28-2/Estradiol; 50-81-7/Ascorbic Acid; 73-31-4/Melatonin; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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